APPLICATION OF MOLECULAR BIOLOGY IN exposing the genome for transcription

MEDICAL VIROLOGY and replication.

4. Macromolecular Synthesis / Eclipse
General Characteristics of Viruses
Period
• Viruses are obligate intracellular - stage where the genetic
parasites unable to self-replicate. material is replicated but intact
virions are not yet detectable.
• Once inside living cells, viruses induce
the host cell to synthesize virus a. Viral DNA or RNA
particles. serves as template for
mRNA production
• The genome is either DNA or RNA
(single or double stranded). b. mRNA codes for viral
protein and enzymes
• Viruses range in size from 25 to 270 nm. necessary for nucleic
• The classification of viruses is based on acid synthesis.
nucleic acid type, size and shape of 5. Assembly / Maturation Stage
virion, and presence or absence of an - Genetic material is assembled
envelope. into a protein coat.
Viral Replication / Infectious Cycle 6. Release
- Viruses are then released from
APUMAR the host cell.
1. Attachment a. Cell lysis - naked viruses
2. Penetration lyse host cell and leave
through a hole in the
3. Uncoating plasma membrane.
4. Macromolecular Synthesis b. Budding – intact virion
pushes outward from a
5. Assembly
host’s membrane.
6. Release

APUMAR

1. Attachment / Adsorption

- attachment of the virus to a specific

receptor on a host cell.

2. Penetration

- entry of the virus to the host cell

3. Uncoating
- occurs when there is either separation
of capsid from the genome or
rearrangement of capsid proteins
VIRAL STRUCTURE

1. Virion – the entire viral particle

2. Capsid – the protein coat that encloses

the genetic material

3. Capsomer – the protein subunit that

makes up the capsid

4. Nucleocapsid – composed of capsid and

genetic material

5. Envelope – outer coating composed of 3. Based on Envelope:

phospholipid bilayer
Present or Absent

NAKED VIRUSES ENVELOPED VIRUSES

Enviromentally STABLE Enviromentally LABILE

Destroy by LYSIS Modifies cell membrane

during replication; release
by budding and occasionally
cell lysis.

Can easily spread by

Classification of Viruses fomites, hand – to – hand
contact, dust and small
1. Based on Nucleocapsid:
droplets; can dry out and
Each nucleocapsid contains a nucleic acid core retain infectivity.
surrounded by a protein coat, the CAPSID
(which consists of many subunits named
CAPSOMERES); the capsid symmetry is either: DNA VIRUSES
• Helical Rules about DNA Viruses:
• Icosahedral ◦ All are dsDNA except: PARVOVIRUS
(ssDNA)
• Complex
◦ All are Icosahedral except: POXVIRUS
2. Based on Nucleic Acid:
(complex)
Each virus contains only one kind of nucleic acid
◦ All are enveloped except (PAP) –
(DNA or RNA), containing the entire genome;
(Papovavirus, Adenovirus, Parvovirus)
nucleic acid in viruses are either:
– naked either resistant
• Singe stranded or double stranded
◦ All multiply in the nucleus except
• Linear or circular POXVIRUS (cytoplasm)
DNA VIRUSES “PaPaAdPoHeHe” HUMAN PAPILLOMA VIRUS

“Papovavirus, Parvovirus, Adenovirus, HPV 1 (Plantar Warts)

Poxvirus, Hepadnavirus, Herpes Virus”
HPV 2 & 4 (Common Warts)

HPV 6 & 11 (Sexually Transmitted Venereal

PAPOVAVIRIDAE Warts)

Members:

Papillomavirus (PA) – common warts

Polyomavirus (PO)

Simian Vacuolating Virus (VA)

Thus, its name PAPOVA

Chronic Form of Warts
Double stranded DNA, Icosahedral, Naked, 45-
Epidermodysplasia verruciformis / TREE MAN
55nm
- Vulnerable to HPV warts

HUMAN PAPILLOMA VIRUS

TRANSMISSION:
- viral infection that’s passed between people
through skin – to – skin contact. - Direct contact
- Sexual contact
- There are 100 varieties of HPV, more that 40
of which are passed through sexual contact Genital infections: associated with neoplastic
lesions including cervical carcinoma
- VIRAL INCLUSION BODIES
(oncogenic) (HPV 16 & 18)
Cytomegalovirus OWL’S EYE
(CMV) INCLUSION
(Basophilic Inclusion) JC – PML VIRUS
Human Papilloma KOILOCYTES
Virus (Papanicolaou (PAP) - Human polyomavirus 2
Smear)
- Commonly referred to as JC Virus or JOHN
Herpes Simplex Virus COWDRY TYPE A
CUNNINGHAM VIRUS
(HSV) BODIES seen in
Varicella Zoster Virus TZANCK SMEAR - PML or PROGRESSIVE MULTIFOCAL
(VZV) LEUKOENCEHALOPATHY
Rabies NEGRI BODIES
(Eosinophilic
Inclusion Bodies)
BK VIRUS
seen in Neurons
Smallpox GUARNERI BODIES - relatively related to JC – PML Virus
Yellow Fever Virus TORRES
COUNCILMAN - typically associated with patients who have
BODIES kidney transplant or renal diseases
ADENOVIRIDAE - Caused by types
8, 19, & 37
- Their name derives from their initial
- Characterized by
isolation from human adenoids in 1953
acute
- Serotypes 1 – 8, 11, 21, 35, 37, 40 conjunctivitis,
(commonly isolated in infections) followed by
keratitis that
- Classified into 2 genera: usually resolves in 2 weeks but may
a. Aviadenovirus - infects birds leave subepithelial opacities in the
cornea for up to 2 years
b. Mastadenovirus – infects
mammals Adenovirus

- Naked, icosahedral, dsDNA, 70-90nm - Can remain viable for several weeks on
sinks and hand towels as a source of
- Has 49 serotypes transmission

Gastrointestinal Disease
Human Adenovirus - Types 40 & 41 associated with infantile
- Divided into 6 groups (A-F) gastroenteritis (5 – 15% cases of viral
gastroenteritis in young children)
Group C
Other diseases:
- Persists as latent infections for years in
adenoids and tonsils and are SHED IN - Types 11 & 21 – acute hemorrhagic
FECES for many months after initial cystitis in children
infections - Children receiving liver transplants may
develop adenovirus hepatitis in the
Eye Infections allograft
- Children with heart transplant may
- Mild ocular involvement may be part of
develop myocardial adenovirus
the respiratory – pharyngeal syndromes
infections and are at risk of graft loss
Pharyngoconjunctival Fever - Patients with AIDS may suffer
adenovirus infections
- Occurs in outbreaks such as at
children’s
summer camps
HERPESVIRIDAE
(SWIMMING
POOL - Spherical, 150-200nm, Icosahedral,
CONJUCTIVITIS) Double stranded DNA
associated with
types 3 & 7 - Produces latent viral infection in (WBCs
and peripheral nerves)
Epidemic Keratoconjunctivitis
- Reactivation – associated with
- Most serious disease, occurs mainly in immunosuppressed patients, with
adults and highly contagious. underlying conditions and those
 undergoing chemotherapy or HERPETIC KERATITIS & HERPETIC WHITLOW
corticosteroid therapy.
- Infects fingers (occupational hazard)
HERPES SIMPLEX VIRUS – 1 (ORAL STRAIN) - Seen in AIDS

- Mild infection and less

resistant to treatment
- TRANSMISSION:
through active ulceration
of the mucous
membranes
- Cause infections ABOVE THE WAIST
Varicella – Zoster Virus (VZV)
- Associated with: gingivostomatitis,
ulcerative mouth lesions and fever - Agent of varicella/chicken pox, herpes
blisters zoster, or shingles (a reactivation form
- May spread to the lips and cheeks of latent varicella)

chicken pox
HERPES SIMPLEX VIRUS – 2 (GENITAL STRAIN)
- A childhood disease
- Generalized skin rash with raised, fluid
filled lesions

Epstein – Barr Virus (EBV/HHV – 4)

- Agent of INFECTIOUS
- Cause infections BELOW THE WAIST MONONUCLEOSIS
- 80 – 90% of genital herpes, a common - Member of subfamily
STD Gammaherpesvirinae
- SIGNS: fever, malaise, inguinal lymph - EBV SHED IN SALIVA
adenopathy (severe case) and transmitted
- Primary lesion appears in: vagina, through oral contact
thus called KISSING
cervix, glans or penile shaft, recurrent
lesions may occur DISEASE
- Neonatal HSV-2 is acquired during
delivery. Attack the infant’s CNS

Other infections caused by HSV:

Cytomegalovirus (CMV/ HHV – 5)

- Formerly known as Salivary gland virus

- Member of the family
Betaherpesvirinae
- Opportunistic infection
- Transmitted through direct contact with
saliva, blood transfusion, organ
transplant
Human Herpesvirus Type 6 (HHV – 6) POXVIRIDAE

- Member of the subfamily
Betaherpesvirinae
- 1st known as Human
Lymphotropic Virus detected
infecting B cells
- Isolated in saliva and
mononuclear cells
- Transmission: Respiratory route
- Agent of “exanthema subitem”
or “roseola” known as the “sixth
disease”
- Benign childhood disease (6
months – 3 years)
Classic Childhood Exanthema
Ali Maow Maalin is the last case of smallpox in
Somalia, 1977
- Largest and most complex viruses, oval
or brick shaped or ellipsoid (400 nm x
230 nm)
- External surface shows ridges, contains
core and lateral bodies
- Double stranded DNA,
enveloped with multiple
membranes
- Family members: Variola – smallpox
virus; vaccinia virus - agents of
cowpox and monkey pox.

NUMBER NAME ETIOLOGY

1ST disease Measles Measles virus Monkey pox infection
(Rubeola)
2nd disease Scarlet Fever Streptococcus
pyogenes
3rd disease Rubella Rubella virus
4th disease Duke’s No longer
Disease accepted as a
distinct
disorder
5th disease Erythema Parvovirus
Infectiosum B19
6th disease Roseola HHV – 6 & - Caused by a species of Orthopoxvirus
infantum HHV – 7 - 1st recognized in captive monkeys in
1958
- Human infections with the virus were
discovered in 1970s in West Africa and
Central Africa
- Acquired by direct contact with wild
animals
Cowpox infections
- Caused by a species of Orthooxvirus
- Milder form of pox diseases that occur
in cattles
- Human infection occurs by direct
milking, and lesions of milkers is usually
confined in the hands
Buffalopox infections
Buffalo virus
- A derivative of vaccinia virus that has
persisted in India in water buffalo
- Can be transmitted to humans
Molluscum Contagiosum
- Benign epidermal tumor that occurs
only in humans
- Causative agent: Molluscipoxvirus
genus
- Not transmitted to animals
- Sexually transmitted and is seen in AIDS
Tanapox & Yaba Monkey Tumor Poxvirus
infections
Tanapox
- Common skin infections in parts of
Africa mainly in Kenya and Democratic
Republic of Congo
- Natural host is monkey
- Classified as the Yatapoxvirus genus
which is morphologically similar to
Orthopoxvirus
- Human infection: via direct contact
PARVOVIRIDAE
- Single-stranded DNA, naked
icosahedral symmetry (18-26 nm in dm)
- Extremely resistant to inactivation
- Stable at pH 3 and 9, withstand heating
at 56oC for 60 minutes
2 sub-families:
◦ Parvovirinae – infect vertebrates
(Genus Parvovirus and Erythrovirus)
- Able to replicate
autonomously in rapidly
dividing cells
◦ Densoviriniae – infects insects
(Defective members, depends on a
helper virus for replication [adenovirus
or herpesvirus])
Parvovirus B – 19
- Known to infect humans
 - Only member of genus Erythrovirus Transient Aplastic Anemia

Canine parvovirus - May complicate chronic hemolytic

anemia (Sickle cell disease,
- Infects dog
Thalassemia, and acquired hemolytic
anemias in adults)
- Occurs after bone marrow (BM)
Human Disease Associated with B19 transplantation
Parvovirus - Symptoms: abrupt cessation of RBC
Syndrome Host or Condition Clinical synthesis in BM, reflected in the
Features absence of erythroid precursors,
Erythema Children/ Adult Cutaneou accompanied by rapid worsening
Infectiosu s rash/ anemia
m (5th Arthralgia
disease) -arthritis Pure Red cell Aplasia
Transient Underlying Severe - B19 may persist and cause chronic
aplastic hemolysis acute suppression of BM and chronic anemia
crisis anemia in immunocompromised patients
Pure red immunodeficiencie Chronic
- Severe anemia. Patients depends on
cell aplasia s anemia
blood transfusion
Hydrops Fetus Fatal
- Observed in patients with AIDS,
fetalis anemia
malignancies, Organ transplants,
congenital deficiencies.
Parvovirus Disease Association
Infection during pregnancy
Erythema Infectiosum (5th disease)

- A common childhood exanthem

- Mode of Transmission: Respiratory route;
Parentally (blood transfusion); vertically
(mother-fetus)
- Incubation period: 1 – 2 weeks
- Clinical features: Fever, unique slapped-
cheek rash. Has affinity to RBC - Pose serious risk to fetus – hydrops
precursors which may lead to anemia fetalis and fetal death due to severe
anemia
- Fetal death occurs during pregnancy
SIMPLIFIED ALGORITHM OF DNA VIRUSES