Classification of viruses

Viruses could be classified according to:

1) Structure: DNA or RNA (most satisfactory for
microbiologists).
2) Morphology: Icosahedral, helical or complex,
also enveloped or none, and others, picorna virus
(small), togavirus (cloak), coronavirus (crown),
rhabdovirus (rod).
3) Disease: Hepatitis virus, encephalitis virus, and
influenza virus (most satisfactory for medicine).
4) Tissue (tropism): Adenovirus (glands),
enterovirus (intestine) or myxovirus (mucous
membranes).
• Host - virus interactions (pathogenesis):
A)Local infection
• Occurs at portal of entry
• No viremia

1- Skin: e.g. warts caused by papillomavirus.

2- Respiratory tract infections affecting the

mucous membranes e.g. influenza and common
cold.

3- Alimentary tract e.g. more than 50% of diarrhea

in infants are caused by rotavirus.
B) Systemic infection:
• After primary replication at the site of entry, the
virus passes through lymphatics, blood (viremia),
tissues or nerves, reaching the target tissue that
has specific receptors for the virus (tropism) e.g.
hepatitis, measles, and poliomyelitis.
• Administration of neutralizing antibodies before
the viremic phase could prevent development of
the disease.
• Local infections are characterized by short
incubation period and short lasting immunity.
• Systemic infections are characterized by long
incubation period and long lasting immunity.
C) Persistent infection:
• Due to escape of the virus from the host defense
mechanism. It is either:
1- Latent infection: the virus remain hidden
(dormant) in cells in a process known as latency
and most of the time with intermittent reactivation
and development of clinical lesions containing the
virus. e.g. herpes simplex and adeno infections.
The virus is not
detected during latency that may be prolonged for
years with no viral activity, signs, or symptoms.
2- Chronic infection: the virus usually has long
incubation period and is always shedding
 (released from the host body) i.e. can be
detected all the time, during symptoms and in
absence of symptoms.
• Usually caused by RNA viruses e.g. hepatitis C.
• The amount of virus produced is usually less
than in acute infection.
3- Slow infection: are viruses with long incubation
period and slow multiplication.
4- Congenital or teratogenic infection: many
viruses penetrate the placenta during pregnancy
causing congenital defect in the embryo, e.g.
rubella, cytomegalovirus, hepatitis viruses and
HIV.
5- Oncogenic infections (tumor causing):
• Oncogenes are genes that play a role in cell
division.
• Activation of oncogenes or inactivation of oncogene
repressors can cause cancer to develop.
• Viruses cause 20% to 25% of human cancers in
several ways.

• There are 3 types of oncogenic viruses:

1- Some viruses carry copies of oncogenes as part of
their genomes.
2- Other viruses promote (activate) oncogenes already
present in the host
3- Other viruses interfere with normal tumor
repression when they insert into repressor genes.

• Examples:
• DNA viruses: HBV, Epestein Barr virus & HSV-2
• RNA viruses: HCV & HTLV human T lymphotropic
viruses
In case of RNA tumor viruses, viral RNA acts as a
template for synthesis of viral DNA through the
action of reverse transcriptase. The DNA copy of
the viral RNA is integrated into the host cell
chromosome.
• Epidemiology of viral infections:
1) Direct contact (sexual transmission): e.g.
herpes simplex virus type 2, HIV and to less
extent hepatitis B.

2) Droplet infection (respiratory): e.g. adeno,

influenza, common cold, measles, mumps,
rubella, rhino and corona viruses.

3) Oral-fecal infection (feces-flies-food-finger -

4F): e.g. poliomyelitis, rota and hepatitis A
viruses.

4) Skin puncture: through

- injection: e.g. hepatitis B virus
- arthropod: e.g. yellow fever virus
- animal bite e.g. rabies virus
 Diagnosis of viral diseases
• Clinical symptoms are enough in most cases,
however, in some cases laboratory diagnosis is
necessary e.g.
- In case of pregnant lady infected with rubella, it
determines whether legal abortion is to be
carried out or not.
- In diseases associated with high mortality e.g.
AIDS, yellow fever.
- In chronic carriers e.g. hepatitis B & C.
- In nosocomial infections e.g. influenza.
• Laboratory diagnosis of viral infections
1. Direct detection of virus
• Electron Microscopy (Magnification : 50,000 -
400,000)
• Light Microscopy “Inclusion Bodies”
• Antigen detection tests
• Molecular Methods: PCR & Nucleic Acid Probes

2. Serology ((Ag-Ab reaction):

1- Detection of IgM: Earliest Ab to appear, only
present in recent infection.
2- Rising Ab Titer: Four fold increase over the course
of infection from the acute phase into the
convalescence.
Using techniques such as:
- Enzyme- linked Immuno-Sorbent Assay (ELISA)
- Radioimmunoassay (RIA)
- Complement FixationTest
- Immunofluorescence (Fluorescent antibody
technique)
- Haemagglutination Inhibition,
Fluorescent antibody staining
Detection of viral antigens by serology
3. Virus Isolation (Indirect detection)
Cultivation of viruses
Viruses grow only in living cells, which may be:
I) Chick or duck embryo
Advantages:
i- inexpensive
ii- among the largest of cells
Iii- free of contaminating microbes
The virus is allowed to grow in one of the
following cavities within the fertilized egg:
a) Embryo e.g. yellow fever virus.
b) Amniotic sac: e.g. influenza virus.
c) Chorioallantoic membrane: e.g. pox and herpes
viruses.
Chick embryo
II) Tissue culture
• Animal or human tissue culture pieces treated
with trypsin to separate the cell.
• They are grown in presence of growth medium
containing serum.
• A monolayer or sheet of cells is formed on the
flat surface of the container (glass or plastic
bottle or tube).
• There are two types of tissue cultures:
a) Diploid cell lines: are created from embryonic
animal, plant, or human cells (diploid number of
chromosome) that have been isolated and
provided appropriate growth conditions (e.g.
fibroblasts from human embryo tissue).
 The cells in diploid cell culture grow rapidly
and generally last no more than about 50
generations (cell divisions) before they die.
b) Continuous cell lines: are longer lasting
because they are derived from tumor cells
and can be subcultured indefinitely e.g. HeLa
cells (named after a woman named Henrietta
Lacks, who died of cervical cancer in 1951)
derived from the carcinoma of the cervix.
 Tissue culture

a) Diploid cell lines

b) Continuous cell lines
III) Intact animal
Rats, mice, guinea pigs, rabbits & pigs have been
used to culture and study animal viruses,
e.g. the white suckling mouse is widely used for
encephalitis viruses, calves are used for pox virus.

Disadvantages
Maintaining laboratory animals can be
1) difficult, 2) expensive, and 3) this practice
raises ethical issues for some.
4) Cultivation in animals has the disadvantage of
easy transmission of infection.
Cultivation of animal viruses
• Detection of viral growth
1)Cytopathogenic or cytopathic effect (CPE):
Observed by light microscope.
- Cell death (poliovirus),
- Cluster formation (adenovirus),
- Giant cell formation (Cell fusion or syncytia)
(measles and mumps viruses)
- Cell transformation (tumor viruses)
- Inclusion bodies: They are aggregates or just
sites of replication of the virus
e.g. Cytoplasmic Negri bodies in brain cells
of rabies infected animal.
Negri bodies in brain cell
2) Hemadsorption:
Viruses which contain hemagglutinin spikes e.g.
influenza virus are able to form clumps of RBCs if
added to the tissue culture.

3) Immunofluorescence:
Infected cells are detected by fluorescence.
Haemadsorption
Immunofluorescence
Fluorescence microscopy can be used to quantify the
. percentage of infected cells
.Green: Zika virus infected cells; Blue: cell nuclei
 . High-resolution microscopy can be used to visualize sites of viral replication
.Green: Zika virus infected cells; Magenta: endoplasmic reticulum; Blue: cell nuclei
• Quantitative determination of virus
1) Measurement of viral antigen (total count =
active + inactive)
a- electron microscopy and hemagglutinin.

2) Measurement of infectivity (active only)

a- cultivation and enumeration of CPE.
b- animal inoculation and determination of lethal
dose 50 (LD50) or infective dose 50 (ID50).
Antiviral treatment Strategies
• Treatment of viral infections
• Since viruses are metabolically inactive, it is
difficult to find antiviral chemotherapeutic
agents.
• However, few antiviral drugs are in clinical use
for example:
1) Agents preventing attachment: e.g.
neutralizing antibodies.

2) Agents preventing uncoating: e.g.

Amantadine and Rimantadine used for
prophylaxis against influenza type A.
3) Agents inhibiting the replication:
a- Azidothymidine (AZT): thymidine analogue
that inhibits the HIV by inhibiting its reverse
transcriptase. AZT reduces the morbidity and
mortality in AIDS patients, however it is very
toxic to lymphocytes and very expensive.

b- Dideoxyinosine (DDl): the same as AZT, but

less toxic.

c- Purine and pyrimidine analogues

- Acyclovir: inhibits herpes simplex virus by
inhibiting virus specific DNA polymerase.
Used locally for herpatic ulcers and parentrally
to treat serious systemic infections e.g. herpes
encephalitis.
- Vidarabine & cytarabine: the same as acyclovir.
- Ribaverine: used as aerosol for treatment of
influenza virus infections. It acts by interfering
with mRNA synthesis.

d- Interferons: They are 3 types (α- , β – and

gamma)
- Natural proteins produced by viral infected cells.

- Non specific i.e. acting against several viruses

(DNA or RNA) except gamma- interferon which
is specific.
- They are species specific i.e. human interferon
protects humans only.

- Act by inhibiting the translation by viral mRNA

indirectly, by attaching to certain cell surface
receptors triggering the formation of
intracellular kinase, without affecting the
translation of human cellular mRNA.

- Used mainly for:

1- Prophylaxis in hepatitis B to delay the
appearance of liver cancer.
2- Treatment of hepatitis C.
I- DNA Viruses
 Poxvirus

Animal
cells Bacteria Viruses Proteins Atoms

10-2 10-3 10-4 10-5 10-6 10-7 10-8 10-9 10-10

(1 cm) (1 mm) (1 µm) (1 nm) (1 ))

Light microscope

Electron microscope

X-ray

NMR
Vertebrate DNA Viruses
 Pox Viruses) 1
• Small pox (Variola), cow pox & Vaccinia:
antigenically related.
• Molluscum contagiosum causes benign skin warts
(shiny painless papules).
 Small pox (Variola) ‫الجدرى‬

• Large brick
shape,
enveloped.
• Core: linear
DS DNA
enclosed in
an inner
membrane.
 The smallpox virus consists of one molecule of double stranded DNA
contained in a core (red). In this illustration, the virus is tilted, showing
the rounded biconcave brick shape of the core, in whose depressions
nestle the "lateral bodies" (purple).
• Two variants: variola major (more fatal) and variola minor.
• It replicates in the cytoplasm forming Guarnieri's inclusion bodies.
• The disease shows a very characteristic skin vesicular rash.

– T
 Eradication of small pox was successful
because:
1- Human is the sole host.
2- Single stable serotype protects against all forms of
infection.
3- Visible pustules allow disease control by quarantine
and vaccination of contacts.
4- No chronic or asymptomatic carriers.
5- Stable and inexpensive vaccine is available.

Vaccination
1- Calf lymph vaccine.
2- Lyophilized vaccine (Egg vaccine)
• Both vaccines are prepared from Vaccinia virus and
are applied intradermally by scratching.
 Human Herpes viruses) 2
Characteristics
• Large enveloped icosahedral with linear ds DNA.
• Envelope contains specific antigenic glycoprotein
spikes.
• Replicate in the nucleus.
• Show latent infection (persist indefinitely in
infected hosts with periodic reactivation
especially in immunosuppressed patients).
• They are susceptible to antiviral chemotherapy.
• May cause cancer i.e. oncogenic viruses (HSV-2
& EBV).
• Classification
a- Herpes simplex virus (HSV) types 1 & 2.
b- Varicella Zoster virus (VSV).
c- Epstein-Barr virus (EBV).
d- Cytomegalovirus (CMV).
A- Herpes simplex (HSV)
(Cold Sore) ‫ااالهاربسأو ااالحرارة‬
HSV showing glycoprotein in form of spikes and
envelope surrounding an icosahedral capsid
containing the ds DNA genome
• HSV-1 & HSV-2 have the same DNA homology,
antigenic determinants, tropism and symptoms
but can be differentiated serologically.

• Location and Transmission of infections

1) HSV-1
- Prevalent in upper part of body (head, throat &
chest).
- Transmitted by contact (kissing and sharing
glass).
- Primary infection in 2-3 years old children
followed by a possible autoinfection to other
parts of skin or eyes.
2) HSV-2
- Prevalent in the lower part of the body (genitals)
- Transmitted to adults by sexual contact & to
neonates during pregnancy or delievery.
 Herpes simplex virus (HSV) types 1 and 2

Prevalent in
the upper
part of the
body

Prevalent in
the lower part
of the body
• Pathogenesis
Initially infect & replicate in mucoepithelial cells
& then establish a latent infection in enervating
neurons, trigeminal ganglia (HSV-1) & sacral
ganglia (HSV-2).

1) HSV-1
- Primary infection: painful ulcers
(gingivostomatitis).
- Recurrent infection: herpes labialis at lips
borders (cold sores), infection of fingers
(whitlow) or eye infection (keratoconjunctivitis)
which may led to blindness & encephalitis with
50% mortality.
Gingivostomatitis
Cold sores
Herpetic whitlow
2) HSV-2
- Appears as painful ulcers on the external genitalia of
both male & female. It
is associated with fever and lymphadenopathy.

• Recurrence usually at the same primary site & is

induced by fever, local trauma, sun light, emotional
stress or menstruation.

• Recurrence occurs in spite of high titer of circulating

Abs (The virus can also spread from one cell to
another without entering the extracellular space and
coming in contact with humoral Abs) i.e. protection
mainly through cell mediated immunity (cytotoxic T
cells and macrophages kill infected cells).
• Laboratory diagnosis
1- Tzanck test: Scrapings from the lesions show
multinucleated giant cells with internuclear
inclusion bodies.
2- Tissue culture: Demonstration of cytopathic
effect on human diploid fibroblasts.
• Treatment
- Acyclovir (oral)
- Idoxuridine, vidarabine & acyclovir ointments:
for herpatic keratitis.
- I.V. acyclovir: for encephalitis.

These drugs act against the replicating virus

(they are incorporated into the DNA as it is
copied & inhibit DNA polymerase) and therefore
they are ineffective against latent virus.
- Why cortisone is contraindicated as anti-
inflammatory?
 B- Varicella-Zoster (VZV)
VZV causes varicella (chickenpox) with recurrence
(latency) or reactivation in sensory nerve ganglia
causing zoster (shingles) i.e. one virus causing
two different diseases.

i) Varicella (Chickenpox)‫ااالجديري‬
Transmission: Usually in winter by respiratory
droplets & occasionally by skin contact.
Pathogenesis:
- The disease occurs mostly in children (mild or
even asymptomatic).
- Initial replication of the virus occurs in the
respiratory tract.

- First symptoms include fever, malaise, headache

and abdominal pain followed by viremia
characterized by a skin vesicular rash (vesicles
containing the virus = pox). These vesicles
(papules) are characteristic for chicken pox &
start on the scalp, face or trunk causing severe
itching then going to extremities (limbs) & mucous
membranes such as oropharynx, conjunctiva and
vagina.
- Vesicles of chicken pox rarely leave scars while
small pox usually leaves scars (disease is very
mild as compared to chickenpox).

- The disease is more severe in adults, neonates

and immunocompromised patients causing
complications such as pneumonia (the virus is
shed in respiratory secretions) & encephalitis.

- Infection usually develops life long immunity to

varicella (but not to zoster).
 ii) Zoster (shingles)
‫ااالعصبااالمكشوف– ااالعصبااالحىا – ااالحز اما ااالنارى‬
• Recurrence after many years of the primary
infection in sensory nerves & ganglia.
• Zoster is characterized by severe pain (caused by
viral inflammation & destruction of sensory
nerves & ganglia) followed by appearance of
vesicles (usually in crops) in the enervated area,
usually unilateral in trunk.
• Laboratory diagnosis
1- Tzanck test: Scrapings from the lesions show
multinucleated giant cells with internuclear inclusion
bodies.
2- Tissue culture: Demonstration of cytopathic
effect on human diploid fibroblasts.
3- Immunofluorescence technique: using epithelial
cells scraped from the base of vesicles.

Prevention and Control

• A live-attenuated vaccine is recommended for
new born.

Treatment
For chicken pox: Acyclovir is the drug of choice.
Famcyclovir & valacyclovir have greater activity.
Calamine lotion have soothing effect.
For zoster: Oral acyclovir.
 C- Epstein- Barr Virus (EBV)
EBV is associated with two main diseases:
1- Infectious mononucleosis (IM) or kissing disease.
2- African Burkitt lymphoma (ABL). It is also
associated with nasopharyngeal carcinoma
& B-cell lymphoma.

1- Infectious mononucleosis (IM)

- Kissing disease as transmitted by saliva.
- Latent in B- lymphocytes.
- Reactivation starts as pharyngitis with gross
enlargement of tonsils, lymphadenopathy, fever
& malaise, rarely fatal.
 Cervical lymphadenitis

Gross tonsillar
enlargement with a
white exudate
- Chronic EBV infection may result in:
a) persistent low grade fever & fatigue.
b) lymphomas in immunosuppressed patients.

Treatment:
• Aspirin is usually enough to control the pain
caused by sore throat and lymphoadenopathy.
• Corticosteroid course for less than 14 days, in
cases of pharyngeal oedema and severe
abdominal pain due to splenomegaly /
lymphoadenopathy.
 2- African Burkitt lymphoma
- Characterized by a poorly differentiated B-cell
lymphoma of the jaw & face endemic to children
of malarial regions in Africa.
• African Burkitt lymphoma is a cancer of the
lymphatic system (especially B- lymphocytes).

Laboratory diagnosis
a) Non specific:
1- Demonstration of atypical lymphocytes.
2- Paul-Bunnel (monospot test): Heterophile IgM
antibodies in patient serum agglutinate sheep &
bovine RBCs but not guinea pig kidney cells.
b) Specific:
- DNA probe for patient peripheral lymphocytes.

African Burkitt lymphoma

 D- Cytomegalovirus (CMV)

• CMV has the largest genome of all herpes viruses

and appears only to replicate in human cells.
• Infects 2.5 % of new borns & 50% of adults in
developed world.
• Transmission: Orally, sexually, congenitally & by
blood transfusion.
 Pathogenesis
- Multinucleated cells (syncytia) with
characteristically staining inclusions.
- Cell mediated immunity is essential in limiting the
disease due to cell to cell spread of the virus.
- Latency in mononuclear lymphocytes.
- Usually asymptomatic & reactivation occurs in
immunocompromised patients.
- In adults, reactivation usually leads to pneumonia
or disseminated disease (hepatitis, encephalitis,...).
• Congenital abnormalities in neonates include
hepatospleenomegaly, microcephaly or mental
retardation (CMV is the most common intrauterine
infection associated with congenital defects).
• Laboratory diagnosis
• CMV could be isolated from several body secretions
including saliva, blood, tears, milk, feces, semen, vaginal
& cervical secretions.
• Detection of multinucleated (cytomegalic) cells with
internuclear inclusion bodies.
• Detection of characteristic CPE after culture on human
diploid fibroblasts.
• Increase in specific Ab titer (4- fold increase).
• DNA probe.
Syncitium Formation
uninfected
cells

activated
fusion protein

budding
virus

syncytium
Lung section showing
cytomegalic cells
with internuclear
inclusion bodies.

• Treatment : Ganciclovir (DNA polymerase

inhibitor)
• Prophylaxis: Live attenuated vaccine that
induces both humoral & cellular immunity.
 Papovaviruses) 3
• Small icosahedral naked DS DNA viruses.

A) Papillomaviruses (HPV) ‫ااالسنطة أو ناافرة ااالحمار‬

- Transmitted by close contact.
- Infect epithelial cells leading to benign outgrowth
in form of warts in hand, foot, head & neck or
anogenital.
- Persistent cervical infection may result in
cervical carcinoma.
- Treatment:
- Warts are treated surgically.
- Destruction of the wart tissue with laser
vaporization or cytotoxic chemicals such as
podophyllin or trichloroacetic acid.
- Drug treatment by Cidofovir or Interferon.

- Prophylaxis:
• Gardasil vaccine contains viral capsids from the
four most common HPV types: 6 & 11 (causing
genital warts), 16 & 18 (causing cervical cancers).
• A second vaccine, Cervarix, contains only two
capsid types and is protective against infection
with the high risk HPV types: 16 & 18.

B) Polyomaviruses
Rarely cause kidney or lung infections in
immunocompromised patients.
 Adenoviruses) 4
• Icosahedral naked DS DNA viruses.
• Induce latent infection.
• Only 42 out of 100 serotypes infect humans.
• Transmitted by droplets, contact or oral- fecal.
• Most common diseases are:
a) Acute pharyngitis & pneumonia.
b) Pharyngoconjunctivitis, usually derived from
swimming pools in summer.
c) Conjunctivitis or keratoconjunctivitis (associated
with preauricular lymphadenopathy and watery
discharge).
d) Acute hemorrhagic cystitis in children.
e) Gastroenteritis.
Conjunctivitis
Uninfected
cells

Cells
infected
with
adenovirus
- Prophylaxis:
1- Live, attenuated adenovirus vaccine is used
to produce good neutralizing antibody
response.
2- Live, unattenuated adenovirus vaccine types 4
& 7 formulated for oral administration.
II- RNA Viruses
 II- RNA Viruses
1. Picorna: Poliomyelitis, Rhino virus
2. Orthomyxo: Influenza
3. Paramyxo: Parainfluenza, Measles, Mumps
4. Toga: German measles
5. Arboviruses (Flaviviruses): Yellow fever
6. Corona: SARS
7. Reo: Rota virus
8. Rhabdo: Rabies
9. Retro: HIV
Hepatitis: (RNA and DNA), A, B, C, D, E, G
 Picornaviruses- 1
- Small icosahedral naked (non enveloped) positive sense
SS RNA viruses.
- Genomic RNA acts as messenger RNA & is infectious.
- Virions do not contain any enzymes.
- Stable in low pH of stomach, replicate in GIT, & are
excreted in stool (fecal-oral route).

Classification
a) Enteroviruses
1- Poliovirus
2- Cosackie virus
3- ECHO (entero cytopathogenic human orphan) virus.
4- Hepatitis A virus.
b) Rhinoviruses
 A- Enteroviruses
1) Poliovirus ‫شاالل اااألطفااال‬
- Three serotypes

- Oral-fecal
especially water
& milk in children.

- Pathogenesis
Poliomyelitis is
mainly characterized
by flaccid paralysis mostly affecting the lower limbs due
to viral replication in the lower motor neurons
in the anterior of spinal cord.
In low socioeconomic areas most adults are immune due
to repeated unapparent infection & paralytic cases are
restricted to children.
• The virus is detected in feces at any time during the
course of infection.
• Secretory antibodies are transient but could prevent
initiation of infection.
• Serum antibodies block viremic spread to the target
tissues.

- Laboratory diagnosis
1) Isolation of the virus on primate cells (human and
monkey) and demonstration of the characteristic CPE.
2) Rise in antibody titer by:
Neutralization test: Neutralizing Abs are detected from
the fourth day of infection & remain life long
i.e. are responsible for life long immunity.
b) Complement fixation test

- Prophylaxis:
1) Salk vaccine: Formalin killed poliovirus, taken as 3
S.C. injections 4-8
weeks apart.
- Disadvantages:
a) Does not prevent viral
replication in the
intestine
b) Expensive
2) Sabin vaccine: Live attenuated, taken in 3 oral doses
4-8 weeks apart.
- Advantages:
a) Prevent intestinal viral replication (induce
secretory Abs)
b) Pass in stool & led to spread of immunity in the
community.
c) Cheap
d) May cause paralysis in immunodeficient children
 B- Rhinoviruses
• Transmission: by droplets via respiratory tract.

• Pathogenesis:
- Most common cause of common cold & upper
respiratory tract infections, usually nose.
- The release of histamine & bradykinin by infected cells
is the cause of runny nose.
- Infections are self limiting & do not cause serious
disease.
- Immunity is transient due to the large number of
serotypes (more than 100) ) and being mainly due to
Secretory IgA.
 2- Orthomyxoviruses
Influenza A, B & C ‫اااألنفلونزا‬
• Pleomorphic (spherical or tubular) enveloped RNA virus.
Nucleocapsid is helical with negative sense SS RNA.
• The envelope is composed of lipid bilayer with an inner
matrix M protein & outer surface 2 glycoprotein spikes:
hemagglutinin (HA: 1-16) & neuraminidase (NA: 1-9)
(two important Ags).
• Virion contains RNA polymerase.
• Classification into types A, B & C depends on antigenicity
of inner proteins (only A & B are of medical importance).
Antigenic variation
It is common in influenza virus due to changes in HA &
NA. Types of variation are:
1) Antigenic drift: minor changes due to point mutation in
HA gene & affects severity of disease.
2) Antigenic shift: major changes due to recombination
between 2 different strains that results in new antigenic
 type (new HA subtype +/- NA) which usually starts an
epidemic or even pandemic. RNA is divided into 8
segments (in case of influenza A & B), each coding for a
single protein. Consenquently, if two (or more) influenza
viruses simultaneously infect the same individual, then
during replication, these viruses can exchange RNA
segments with one another, thereby creating viruses with
entirely new combinations of genes.

- Pathogenesis
- Influenza A is the most severe & C is the least.
- Influenza (flu) is an infection of the upper respiratory
tract & is transmitted by respiratory droplets.
- After inhalation of influenza virus particles, respiratory
epithelial cells are destroyed by the immune response,
especially cytotoxic T cells & also by the virus itself.
 - HA: binds to receptors on host cells.
- NA: cleaves sialic acid residue of the mucus
facilitating virus penetration into both mucus
secreting & ciliated epithelial cells & destroy them.
This action helps the release of virion particles from
the cells & facilitaties the adhesion of bacteria such
as pneumococci which then easily attacks the
respiratory epithelia (secondary bacterial infection).
- Symptoms:
Chills, high fever (39-40oC), myalgia (muscle aches),
dry cough & severe drowsiness.
- The disease runs its course in 4 to 5 days, then it is
usually self limiting.
- Short life immunity to influenza virus is due to:
1) Continuous variation (shift & drift) of the virus.
2) The virus mostly does not invade the blood.
3) Short incubation period & short disease time.
Secretory IgA and cell mediated immunity play a major
role in protection against influenza virus.
• Prophylaxis: Formalin killed vaccine with the
suspected type A & B variants.
• The host produce antibodies against HA that can
neutralize the virus.

• Treatment
- Amantadine & rimantadine prevent the influenza virus
from uncoating. They reduce both the duration &
severity of flu symptoms in type A influenza infections,
but only if given during the first 24 hours of infection
(may be prophylactic).
- Salicylates & antihistaminics.
- Vitamin C & rest in bed.
• Seasonal Influenza
• Seasonal flu makes its round every year, with the most
severe outbreaks in the fall and winter months. The
viruses that cause seasonal influenza have been
infecting people for many generations, so the human
immune system is usually able to quickly recognize
and fight against this common infection.
However, tens of thousands- mostly the elderly, very
young, and immunocompromised people- die from
seasonal flu annually.

• A new formulation of the seasonal flu vaccine is

created prior to each flu season, because viruses are
always changing.
• Avian flu (Bird flu)
• A highly pathogenic strain of the subtype A/H5N1 that
infect birds which in their turn infect humans where the
infection is often fatal (death rate is high > 50%).
• Pigs, however, express both avian- and human-type
receptors on their respiratory epithelial cells & can be
infected with avian, human and swine influenza viruses.
Therefore, pigs
are considered as the "mixing vessels" in which
reassortment between avian and human influenza
viruses can occur to form a new more dangerous virus
which could result in human-to-human transmission.

• Swine flu (H1N1 Influenza A)

• This virus was originally referred to as “swine flu”
because many of the genes in this new virus were very
similar to influenza viruses that normally occur in pigs
(swine(.
 3- Paramyxoviruses
a) Parainfluenza
b) Respiratory syncytial
c) Mumps
d) Measles

• Common Characters
- Non segmented helical
negative SS RNA.
- Spherical enveloped.
- The envelope carries on its surface 2 glycoprotein
spikes:
- Hemagglutinin & neuraminidase (HN) spike.
- Fusion protein (F) spike that allows the virus to enter
cells by fusion not by receptor mediated endocytosis.
- Some viruses contain RNA polymerase.
 1- Mumps‫ااالنكاف‬
• A highly communicable disease infecting only human.
• Only one serotype.
• Transmission: by respiratory droplets.
• Pathogenesis
- Main cause of acute benign viral parotitis (bilateral or
unilateral swelling of salivary glands especially parotid
glands).
- Systemic infection may occur in pancreas, CNS
(meningitis & encephalitis) & testes (orchitis).
• Laboratory diagnosis
- Isolation of virus from saliva, blood, CSF or urine.
- Serological tests: ELISA or hemagglutination inhibition.

- Prophylaxis
MMR vaccine: live attenuated mumps - measles -rubella
vaccine.
Immumity is life long following infection or vaccination.
 2- Measles (Rubeola) ‫ااالحصبة‬
• A highly communicable disease infecting mainly
children.
• Transmission: by respiratory droplets.
• Pathogenesis
• It replicates initially
in the respiratory
epithelium, then in
lymphoid tissues
leading to viremia and
growth in a variety of
epithelial tissues.
• Infection begins with fever, runny nose, cough &
conjunctivitis.
• Koplik's spots appear, after 2-3 days, on buccal cavity
mucosal membrane (mouth & throat).
• A generalized maculopapular rash extending from head
to the extremities.
• Patient is no longer infectious soon after rash
appearance.
• Post infectious encephalitis: autoimmune disease that
may occur within 2 weeks after the onset of the rash.

• Laboratory diagnosis
- Clinical symptoms.
- Serological tests.

Prophylaxis
- MMR vaccine.
- Live attenuated single measles vaccine.
 4- Toga viruses
Rubella (German measles)
‫ااالحصبة اا لاألمانية‬
• Common Characters
• Positive SS RNA, non
segmented.
• Enveloped icosahedral
nucleocapsid.
• Only one serotype.
• Pathogenesis
- Postnatal rubella: resemble measles in causing fever &
skin rash, but milder with no koplik’s spots & is self
limiting.
• Congenital rubella: infection is very serious in pregnant
ladies as it crosses the placenta. It results in congenital
defects in the fetus (deafness, blindness, splenomegaly,
heart defects & mental retardation), especially during
the first three months of pregnancy.
 Laboratory diagnosis
Serological tests: ELISA or hemagglutination
inhibition.

Prophylaxis
- MMR vaccine.
- Live attenuated single rubella vaccine for girls before
marriage.
Vaccination should be avoided during pregnancy &/or
3 months before pregnancy.
• Immunity is life long following infection or vaccination.
 Comparison between Measles & German measles

Measles German measles

Rubeola Rubella
Paramyxovirus Togavirus
Negative SS RNA Positive SS RNA
Helical Icosahedral
Severe course Mild course
Long duration Short duration
Koplik’s spots No Koplik’s spots
Less severe in pregnancy Severe in pregnancy
 5- Flaviviruses
Arbo (arthropod born) viruses
Yellow fever‫ااالحميااالصفراء‬
• Transmission: by the bite of female Aedes aegypti
mosquito. Usually infection is restricted to tropical
forests (endemic in Africa & South America).
There are 2 types:
a) Urban: transmitted
from man to man by
the mosquito.
b) Jungle: transmitted
from monkey to man
by the mosquito.
• Pathogenesis
• Severe symptoms such as fever, heart & kidney
damage, liver degeneration (jaundice) & massive GI
hemorrhage (black vomit), with mortality over 50% in
epidemics.

Laboratory diagnosis
Serological tests: ELISA or hemagglutination
inhibition.

Prophylaxis
The 17D vaccine (YF-Vax, Stamaril) (live attenuated
& lyophilized) is given I.D. & elicit life long immunity.
 6- Reoviruses
Rotavirus
• Non enveloped icosahedral DS RNA (11 segments)
genome.
• It is the leading cause of
severe diarrhoea among
infants and young children.
• There are seven serotypes
where Rotavirus A is the most
common & causes more than
90% of infections in humans.

• Transmission:
• Oral- fecal route.
• Pathogenesis
- Rotavirus infects cells lining the small intestine.
- Produces an enterotoxin, which induces gastroenteritis,
leading to vomiting & severe watery diarrhea causing
death most commonly through dehydration (up to one
million deaths each year in developing countries).
• Laboratory diagnosis
Enzyme immunoassay.
• Prophylaxis
Live attenuated vaccine taken orally against serotype A.
The vaccine is recommended for infants all over the
world.
Treatment: Mainly through oral rehydration by
water & electrolytes (isotonic glucose/
mineral salts solution).
 7- Rhabdoviruses
Rabies ‫ااالسعاار أو مرضااالكلب‬
• Enveloped helical SS non segmented RNA genome.
• Glycoprotein spikes.
• Bullet shaped.
• Contains RNA
polymerase.
• Transmission
Rabies is a classical zoonotic infection transmitted
to human by a rabid animal bite such as racoons,
squirrels, foxes, dogs, cats & bats (animal
reservoirs).
• Pathogenesis
- Rabies is a fatal disease.
- Incubation period is 1- 8 weeks according to the
site of the bite.
- After the bite, the virus replicates in local muscles
causing itching at the site of the bite.
- The virus infects peripheral neurons & travels up
the spinal cord to the brain where it replicates in
the gray matter.
- The virus then travels from the brain via autonomic
nerves to lungs, kidneys, eyes & salivary glands.
- Characteristic neurological symptoms start by
excitation, hallucinations, followed by descending
paralysis showing photophobia, hydrophobia due
to difficulty in swallowing & respiratory paralysis.
- Last stages are accompanied by convulsions,
coma & finally death due to fatal encephalitis with
neuronal degeneration of brain & spinal cord
(together with respiratory paralysis).

• Laboratory diagnosis
1- Diagnosis depends on the exposure history of
patient & characteristic clinical symptoms of
rabies.
2- Detection of intracytoplasmic inclusions called
Negri bodies (aggregates of nucleocapsids) in
neurons or brain cells of the rabid animal or
postmorteum in the infected person.
Negri bodies in brain cell
• Prophylaxis
A) Pre-exposure
1- Killed virus vaccine for individuals at high risk
such as veterinarians.
2- Vaccination of domestic dogs & cats.
3- Eradication of rabid wild animals.
B) Post-exposure
1- Wound washed immediately with water & soap
followed by alcohol.
2- Vaccination by:
i) Human diploid cell strain: chemically inactivated
virus given as I.M. injections at 0, 3, 7, 14 & 28
days after the bite.
• ii) Duck embryo vaccine: chemically inactivated
virus given as 14 doses.

• Treatment
Once clinical symptoms of rabies begin, death is
inevitable & there is no effective treatment.
 8- Coronaviruses
‫ااالفيروسااالتاجي‬
• Enveloped, non-segmented, SS, (+) sense RNA.
• It is the longest genome of any RNA virus.
• There are now approximately 15 species in this
family, which infect not only human but also
cattle, pigs, rodents, cats, dogs and birds.
- Infected carriers are able to shed viruses into
the environment.
- The interaction of the coronavirus spike protein
with its complementary cell receptor is central in
determining the tissue tropism, infectivity,
and species range of the released virus.
- Coronaviruses mainly target epithelial cells.
- They are transmitted from one host to another
host, depending on the coronavirus species, by
either an aerosol, fomite, or fecal-oral.
• They cause respiratory tract infections that can
range from mild to lethal. Mild illnesses in humans
include some cases of the common cold (which is
also caused by other viruses, predominantly
rhinoviruses), while more lethal varieties can
cause SARS (Severe Acute Respiratory
Syndrome), MERS (Middle East respiratory
syndrome, and COVID-19.

• SARS was first reported in South East Asia in

February 2003. Over the next few months, the illness
spread to several countries (SARS global outbreak
of 2003).
 9- Retroviruses
Human immunodeficiency virus
(HIV) – AIDS ‫يدز‬
‫ اااال‬- ‫نااقصااالمناعة ااالمكتسبة‬
• Characteristics
- Positive sense, SS linear RNA- two copies per
virion (diploid).
- Envelope contains surface glycoprotein
undergoing genetic variation.
- Virion contains reverse transcriptase (to transcribe
DNA from its RNA).
- Integrase (to integrate into the chromosome).
- Protease (for maturation).
Enveloped “Spherical” (HIV)
• Transmission
- Sexually (present in semen & vagina secretions).
- By transfusion of blood or blood products (whole
blood, plasma clotting factors & cellular fractions
of blood) & by contaminated syringes of drug
addicts.
- Transplacentally, breast milk & organ
transplantation.

• Statistics
- Approximately 14000 new HIV infections occur
daily around the world and > 90% of these are in
developing countries.
- In Africa (mostly sub Saharan), there are > 30
million people with HIV infection and > 1 million
new cases of AIDS per year.
• Pathogenesis
- HIV primary target is the activated CD4+ T4 helper
lymphocyte but it can also infect several other cell
types including macrophages.
- HIV enters the cell by fusion of the virus envelope
with plasma membrane.
- Viral RNA-dependent reverse transcriptase
synthesizes a DNA-RNA hybrid molecule, then
degrades the parental RNA while replacing it with
a second strand of DNA.
- Resulting linear molecule of DS DNA is the
provirus which is transported to nucleus &
randomly inserted into host chromosome by viral
enzymes.
- The integrated DNA is translated into viral mRNAs
coding for viral proteins.
- Assembled virion bud through plasma membrane.
- Production of virus is a continuous process,
eventually killing host cell.
• AIDS (Acquired Immuno-Deficiency
Syndrome)
- Initial infection starts with a flu-like illness within
several days to weeks after exposure to the virus.
Symptoms usually disappear within few weeks.
- After the initial infection, many individuals show
symptoms similar to those of infectious
mononucleosis, during which there is a very high
level of virus replication in CD4+ cells.
- Acute phase viremia resolves into asymptomatic
or latent period where the virus is persistent in
lymph nodes possibly for many years (during this
phase, virus is reverse transcribed into DNA & is
integrated into host cell chromosome & so may
remain latent in T cells) .
- Latent period is characterized by persistent
generalized lymphadenopathy, diarrhea & weight
loss.
- AIDS started due to stimulation of virus replication
in CD4 T- cells which may be due to infection with
DNA viruses or other microrganisms. The disease
progresses into the following sequence:
1) Persistent generalized lymphadenopathy (PGL).
2) AIDS- related complex (ARC) showing diarrhea,
fatigue & weight loss.
3) Fully developed AIDS syndrome (due to severe
depletion in CD4 T- cells) characterized by
development of infections & malignancies such
as:
 a) Opportunistic infections: e.g. Candida (thrush
mouth), Pneumocytosis carinii (pneumonia),
cerebrospinal toxoplasmosis, cryptococcal
meningitis, T.B., diarrhea by enterobacteria,
recurrency of DNA latent viruses e.g. HSV, VZV,
EBV & CMV infections.
b) Malignancies: Kaposi’s
sarcoma & non Hodgkin’s
lymphoma.
c) AIDS related Dementia:
deterioration of
intellectual abilities
similar to early stages of
Alzheimer’s disease.
Kaposi’s sarcoma
• Laboratory diagnosis
Usually carried to identify carriers who may transmit
infection to others & to initiate antiviral therapy.
1- ELISA: for screening as it is non confirmatory.
2- Western blot: determines presence of Ab to each
of the viral Ags e.g. core protein. More
confirmatory.
3- Determination of CD4/CD8 ratio.

• Prevention & Control

AIDS is fortunately not highly infectious & control is
mainly through education projects involving
behavioral changes.
.
• Treatment
Anti-Retroviral Therapy (ART), a “combination” of
three to four antiviral drugs to reduce viral
replication:
1- Attachment inhibitors (Enfuvirtide)
2- Reverse transcriptase inhibitors (Lamivudine &
Nevirapine)
3- Integrase inhibitors (Elvitegravir)
4- Protease inhibitors (Saquinavir)

• ART is expensive and generally must be taken on

a strict schedule.
• Studies indicate that the therapy stops the
replication of HIV because strains of the virus are
 unlikely to develop resistance to all of the drugs
simultaneously.
• As long as treatment continues, a patient can live
a relatively normal life; however, treatment is not a
cure, because the infection remains.

2- Treatment of individual diseases associated with

AIDS such as opportunistic infections.
 Hepatitis Viruses
‫ااالتهاابااالكبد ااالوبائي‬

6 Serotypes
• Hepatitis A (infectious hepatitis).
• Hepatitis B (serum hepatitis).
• Hepatitis non A non B: Hepatitis C & E.
• Hepatitis D.
• Hepatitis G.
• Clinical features of viral hepatitis:
- Long incubation period
- Hepatitis viruses mainly replicate in hepatocytes (liver
cells).

- Clinical symptoms
- Fatigue (malaise), abdominal pain & nausea followed
by raise of bilirubin leading to jaundice (obstructive),
dark bile-containing urine, pale stools and there are
elevated levels of liver enzymes (mainly alanine
aminotransferases: ALT including SGOT & SGPT) in
the serum (liver functions are severely impaired).
 1- Hepatitis A (HAV)
• Characteristics
- HAV belongs to the family of picornaviruses.
- Positive sense SS non segmented RNA.
- Non enveloped icosahedral.
- Virion does not contain any enzymes.

- Transmission
- Oral- fecal & virus is shed in feces after about 2
weeks of onset of jaundice.
- HAV are most commonly seen among children
especially in crowded places such as summer
camps.
- Epidemic may occur due to fecal contamination of drinking
water, food and milk---outbreak.
- HAV does not develop chronic infection.

• Laboratory diagnosis
ELISA

• Prophylaxis
Formalin inactivated viral vaccine.

• Treatment
- Hepatitis A immune globulin is used as post-exposure
prophylaxis.
- No antiviral agents are currently available for treating HAV
infections.
 2- Hepatitis B (HBV)
• Characteristics
- Prototype of hepadnavirus family.
- The infective virion morphological form
is called “Dane particle” which has the
following characters:
- Circular DNA, partly SS, partly DS,
non covalently closed genome.
- Enveloped, icosahedral.
- Viral Ags are:
i) HBcAg: core Ag surrounded by DNA
polymerase (reverse transcriptase).
ii) HBsAg: surface or envelope Ag.
iii) HBeAg: minor variant of core Ag.
• Transmission
- Infectious HBV is present in all body fluids of an
infected individual such as blood, semen, saliva
& mother’s milk.
- Transmission is parentral, sexual & transplacental.

• Pathogenesis
Infection may be asymptomatic, acute or chronic
according to the immune status of the individual.
• Acute hepatitis
- In about 2/3 of individuals infected with HBV, the
primary infection is asymptomatic.
- Incubation period of acute hepatitis is 45-160 days.
- Symptoms: nausea, vomiting, malaise, abdominal
pain, jaundice & dark urine.
Chronic he
patitis
• Fulminant hepatitis
In 1-2% of acute hepatitis cases, much more
extensive necrosis of liver occurs with high fever,
abdominal pain leading to liver failure, coma,
seizures & death.

• Chronic hepatitis
- Chronic hepatitis can lead to liver cirrhosis.
- Chronic HBV infection may be the cause of about
80% of hepatocellular carcinoma (HCC) cases.

• Laboratory diagnosis
- Clinical symptoms.
- Detection of hepatitis B markers: HBsAg + HBeAg
+ HBcAb (IgM) indicates active infection case.
Serological tests: Detection of viral Ags & antiviral
Abs by ELISA & RIA.

• Prophylaxis
HBsAg recombinant DNA vaccine: prepared by
genetic engineering in yeast & given as 3 doses
at 2, 4 & 6 months.

• Treatment
- Supportive treatment for acute hepatitis.
- Alpha-interferon for chronic hepatitis.
- Lamivudine (Epivir HBV - Glaxo SmithKlein): a
reverse transcriptase inhibitor that is also
approved for use in HIV infections .
 3- Hepatitis C (HCV)
• Characteristics
- Flavivirus with a positive sense SS non segmented
RNA genome.
- Enveloped, icosahedral.
- Virions do not contain any enzymes.
• Transmission
- Transmission is parentral (I.V. drug abusers, blood
transfusion, blood contaminated razors, organ
transplantation), sexual & transplacental.
- HCV causes chronic hepatitis in 50% of cases &
acute hepatitis in 20% of cases.
- The high incidence of chronic asymptomatic
infections promote the spread of the virus in blood
supply.
• Pathogenesis
- HCV accounts for about 90% of non A non B viral
infections & is the major cause of post transfusion
hepatitis.
- HCV causes acute infection (milder than HBV),
but most probably chronic hepatitis.
- Viremia lasts 4-6 months in patients with acute
hepatitis & > 10 years in those with chronic
hepatitis.
- Chronic hepatitis caused by HCV is more prevalent
than that caused by HBV.
- Symptoms are similar to those of HBV & liver
cirrhosis & hepatocellular carcinoma can also
occur as a result of chronic infection.
- Clinical symptoms & eventual tissue damage
occur due to the effect of the immune system on
infected hepatocytes, especially cytotoxic T cell
response.

• Laboratory diagnosis
- Detection of clinical symptoms.
- Liver function tests for liver enzymes.
- Detection of Abs by ELISA.
- Detection of viral RNA by PCR.

• Treatment
- Supportive treatment for infected liver.
- Alpha-interferon (previously).
- Sofosbuvir (Sovaldi®): Sofosbuvir is an inhibitor of the HCV
RNA-dependent RNA polymerase, which is required for viral
replication.
Sofosbuvir is a nucleotide prodrug that undergoes
intracellular metabolism to form the pharmacologically active
uridine analog triphosphate.

- Harvoni: A combination of ledipasvir and sofosbuvir.

• Ledipasvir: an inhibitor of the HCV NS5A protein, which is
required for viral replication and virion assembly.
• Sofosbuvir
Internet sites for Virology

- http://pathmicro.med.sc.edu/book/virol-ta.htm
- http://www.cdc.gov
- http://www.ncbi.nlm.nih.gov/entrez/query.fcgi
- Google image
 Virology
(PMI 424)

Prof. Dr. Yasser El-Mohammadi Ragab

• Learning Outcomes
1- Describe the general biological and physical
properties of viruses and how they differ from
other infectious agents.
2- Describe the virus structures, function, and
replication.
3- Mention the importance of cultivation of virus in
diagnosis.
4- Describe the virus classification and the major
properties of DNA & RNA viruses.
5- Mention diseases caused by DNA & RNA viruses.
6- Discuss viral pathogenesis, diseases and host
response.
Course Outline

Virology

- Introduction

- DNA viruses

- RNA viruses
 Introduction to Virology

• General properties
A) Definition:
- Viruses are obligate intracellular parasites
infecting man, animal, insects, plants and even
bacteria.
- Viruses cause many of the diseases that are
very common around the world: common cold,
influenza, hepatitis, AIDS, Ebola
And now …. Corona (Covid19).
- The virus must first recognize and bind to host
cell that permits its replication; this is due to
certain legends on viral surface and receptors
on the host cell.

- Viruses are not a living cells due to:

1- No cell wall or cell membrane.
2- Metabolically inactive (no metabolic enzymes).
3- No energy production.
4- No ribosome for protein synthesis.
5- They can neither grow nor respond to the
environment.
B) Size:
• Viruses are the smallest known infectious agents.
• However, prions (sometimes called
unconventional viruses) composed only of
proteinaceous matter, are known to be
responsible for neurological diseases in human
e.g. Creutzfeldt-Jacob and kuru diseases & in
animal e.g. Bovine spongiform encephalopathy in
cattle (Mad Cow Disease).
• Viruses size ranges between 20 nm (parvovirus)
and 300 nm (poxvirus).
• First described as filterable agents as they pass
through bacterial filters.
• Observed only under electron microscope, which
can measure them.
Hypothesis for Prion Action Accumulated
abnormal
proteins kill
neuron, with
prions
spreading to
adjacent
neurons.
C) Structure:
• The virus particle (virion) consists of:
1- Core (genome):
- Composed of either DNA or RNA, single or
double stranded, linear or circular.
- The RNA may be of positive sense (acts as
mRNA) or negative sense (act as anti mRNA).
- The RNA may exist as segmented or non-
segmented strand(s).

2- Coat (capsid):
Shell of protein made of subunits called
capsomeres (composed of one or different
protein types), which are bounded by non
covalent bonds to facilitate release of the
genome during replication.
3- Envelop
- Found in only some viruses.
Composed of phospholipids and proteins
(typically derived from portions of the host cell
membranes), but include some
viral glycoproteins.
• The outer layer (proteins and glycoproteins)
may exist as spikes which may act as legends
for the virus or have certain other activities, i.e.
often play a role in the recognition of host cells.
4- Enzymes:
Found only in very few numbers of viruses.
• The virus if composed of core and coat only
may be termed nucleocapsid or naked virus.
 Structure

• Core
• Coat (Capsid)

 Envelop
D) Morphology (symmetry)
1- Icosahedral: resembling crystal, with several
surfaces, several angles and more than one axis
of symmetry, e.g. herpes virus (enveloped),
adenovirus (non-enveloped).

2- Helical: the genome is arranged in a spiral with

capsomeres arranged around it in a ribbon like.
Helical viruses are usually enveloped e.g.
Influenza virus.

3- Complex: complicated structure, e.g. poxvirus,

which is brick shaped with ridges or tubules on
its surface.
 Morphology (symmetry)

Icosahedral Helical Complex

Icosahedral
 Virion Morphologies

• Genetic material is
DNA or RNA
• Coat is protein

Complex virus
Helical virus Polyhedral virus (bacteriophage)
Virions (Virion Particle)
E) Virus replication:
• The host cell acts as a factory, providing
substrates, energy and machinery for synthesis
of coat proteins, and nucleic acid genomes.
Viruses have evolved many ways to use and
manipulate the host cell for their purposes.
Viruses can regulate cellular enzymes, modify
cellular structure and perturb metabolic
pathways.
Virus replication consists of the following steps:
1) Recognition and attachment to the target cell
(Adsorption):
• Depends on legends of the virus and receptors
in the host cell e.g. the hemagglutinin spikes of
the enveloped influenza virus and the CD4
receptors of the T helper cells for human
immunodeficiency virus (HIV).
• Some viruses use multiple receptors, which may
allow them to invade a variety of cell types as
infection in the host progresses.
• Viruses may prefer certain target tissue
(Tropism), accordingly several viruses may
cause the same disease if they have the same
target tissue e.g. hepatitis viruses and common
cold viruses.
• Specific antibodies could prevent the process
of attachment.

2) Penetration (viropexis):
• Naked viruses are taken by host cell by
endocytosis.
 Enveloped viruses penetrate the host cell either
by fusion of the envelope with the cell
membrane and delivery of the nucleocapsid into
the cytoplasm or by endocytosis.
• Syncytia: some viruses at neutral pH
promote cell-to-cell fusion e.g. measles,
paramyxovirus, retroviruses (HIV), & herpes
simplex virus (all are enveloped).

3) Uncoating:
• Enveloped viruses are usually uncoated upon
fusion to the cell membrane. The virus is then
delivered to the replication site.
Syncitium Formation
uninfected
cells

activated
fusion protein

budding
virus

syncytium
• DNA viruses replicates in the nucleus except
poxvirus.
• RNA viruses replicates in the cytoplasm except
retroviruses (HIV).

4) Synthesis of macromolecules:
• The most important step in virus replication.
Depends on the formation of functional mRNA
capable of binding to the ribosome and being
translated into proteins.
• DNA viruses that replicate in the nucleus utilize
the cell's DNA dependent RNA polymerase to
synthesize their own mRNA (just as the host cell
does), while poxvirus which replicates in the
cytoplasm must encode for such enzyme.
• RNA viruses must encode for enzymes to make
their mRNA from RNA, which involves a
different mechanism.

• Protein synthesis takes place in 2 stages:

• Early stage: synthesis of proteins that inhibit
the host cell metabolism and enzymes
(polymerases) necessary for nucleic acid
replication.
• Late stage: synthesis of protein capsids.
5) Assembly (Maturation):
• Association of cores and coats. Usually starts as
soon as the necessary pieces are synthesized.
• The number of viruses produced and released
depends on both the type and size of virus and
initial health of the host cell.

6) Release:
• Enveloped viruses are released usually by
budding. Each virion acquires a portion of cell
membrane, which becomes the viral envelope
(during synthesis, some viral glycoproteins are
inserted into cellular membranes, and these
proteins become the glycoprotein spikes on the
surface of the viral envelope).
• Naked viruses are released in one of two ways:
Either they may be extruded from the cell by
exocytosis, in a manner similar to budding but
without the acquisition of an envelope, or after
inducing lysis and death of the host cell.
• The time interval after penetration and before
assembly is called eclipse cycle. During the
eclipse cycle infective virion could not be
isolated.
 adsorption
DNA Enveloped Virus Replication
penetration

uncoating
Transcription Translation
synthesis of viral genes
DNA replication
Proteins

Assembly
maturation

budding
Virus Envelopes (Spikes)
Enveloped Virus Budding
Reproduction of
bacteriophage
(Replication or
life cycle)

1- Attachment

2- Penetration

3- Biosynthesis

4- Maturation

5- Release