General Characteristics:

1. Viruses are particles composed of an internal core containing either DNA or RNA ( but not both) covered by a
protective protein coat. Some viruses have an outer lipoprotein membrane, called an envelope, external to the
coat.

2. Viruses are “obligate intracellular parasites” = because they can reproduce only within cells since
they cannot generate energy or synthesize proteins

3. Viruses replicate in a manner different from that of a cells = they don’t undergo binary fission

Comparison of viruses and cells:

Property Viruses Cells

Type of nucleic acid DNA or RNA but not both DNA and RNA
Proteins Few Many
Lipoprotein membrane Envelope present in some viruses Cell membrane present in all
cells
Ribosomes Absent Present
Mitochondria Absent Present in eukaryotic cells
Enzymes None or few Many
Multiplication by binary fission No Yes (most cells)

VIRAL STRUCTURE

spikes

peplos

capsomer

capsid nucleocapsid
nucleic acid core

SIZE & SHAPE = ranges from 20-300 nm in diameter

= shapes are referred to in colloquial terms (ex. spheres, rods, bullets, or bricks)
= in reality, they are complex structures of geometric symmetry
= the shape is determined by the arrangement of the repeating sub-units that form the protein
coat CAPSID of the virus

VIRION = the complete infectious viral particle

NUCLEIC ACID CORE = constitute the genetic material or viral genome w/c can either be DNA or RNA
= located internally & can be either single- or double-stranded DNA or single- or double-stranded
RNA
= nucleic acid could either be linear or circular
= the DNA is always a single molecule which the RNA can exist either as a single molecule or in
several pieces
= viruses are haploid (they contain only one copy of their genes); except for retroviruses w/c are
diploid

CAPSID = protein coat or sheath that surrounds the nucleic acid core
= made up of subunits called capsomers
= functions;
 1. protect the viral genome/genetic material from destructive agents in the external environment
2. introduce the viral genome into the host cell / mediate the attachment of the virus to specific receptors
on the host cell surface

CAPSOMER = protein sub-units of the capsid

= each is consist of one or several proteins
= the arrangement of capsomers gives the virus structure its geometric symmetry
= 2 forms of symmetry:
1. icosahedral – capsomers are arranged in 20 triangles
2. helical – capsomers are arranged in a hollow coil

SPIKES = protein projections that extends from the capsid w/c attach to host cell receptors during the entry
of the virus into the cell

PEPLOS = a lipoprotein projections that extends from the capsid

= ex. Hemagglutinin & neuraminidase spikes

PEPLOMERS = lipoprotein sub-units of the peplos

ENVELOPE = is a lipoprotein membrane composed of lipid derived from the host cell membrane &
protein that is virus-specific
= confers instability on the virus
= enveloped viruses are more sensitive to heat, detergents, & lipid solvents such as alcohol &
ether than are nonenveloped viruses, w/c are composed only of nucleic acid & capsid proteins
= the surface proteins of the virus, whether they are the capsid proteins or the envelope
glycoproteins are the principal antigens against w/c the host mounts its immune response to
viruses; they are also the determinants of type specificity

Atypical Viruslike Agents

There are 4 exceptions to the typical virus as described above:
1. Defective viruses
= are composed of viral nucleic acid & proteins but cannot replicate w/o a “helper’ virus, w/c provides the
missing function
= the ratio of defective to infectious virus particles can be as high as 100:1
= aid in recovery from an infection by limiting the ability of the infectious particles to grow

2. Pseudovirions
= contain host cell DNA instead of viral DNA w/in the capsid
= can infect cells but they don’t replicate

3. Viroids
= consist solely of a single molecule of circular RNA w/o a protein coat or envelope
= cause several plant diseases but are not implicated in any human disease

4. Prions
= are infectious protein particles that are composed solely of protein, they contain no nucleic acid (DNA
or RNA)
= are much more resistant to inactivation by ultraviolet light, heat, & acid than are viruses
= resistant also to formaldehyde & nucleases but are inactivated by hypochlorite, NaOH, &
autoclaving
= hypochlorite is used to sterilize surgical instruments & other medical supplies that cannot be
autoclaved
REPLICATION

Viral Growth Curve

= the first event, the virus disappears (as represented by the solid line dropping to the X axis)
= although the virus particle is no longer present, the viral nucleic acid continues to function &
beings to accumulate w/in the cells (as indicated by the dotted line)
= the time during w/c no virus is found inside the cell is known as eclipse period
= the eclipse period ends with the appearance of virus (solid line)
 = the latent period, in contrast, is defined as the time from the onset o infection to the appearance
of virus extracellularly
= the infection begins with one virus particle & ends w/ several hundred virus particles having
been produced

Stages of the viral growth cycle

Attachment & penetration by parental virion
⇓ EARLY EVENTS
Uncoating of the viral genome
⇓
Early viral mRNA synthesis
⇓
Early viral protein synthesis
⇓
Viral genome replication MIDDLE EVENTS
⇓
Late viral mRNA synthesis
⇓
Late viral protein synthesis
⇓
Progeny virion assembly
⇓ LATE EVENTS
Virion release from cell

= the infecting parental virus particle attaches to the cell membrane & then penetrates the host cell
= the viral genome is uncoated by removing the capsid protein, & the genome is free to function
= early mRNA & proteins are synthesized
= the early proteins are enzymes used to replicate the viral genome
= late mRNA & proteins are then synthesized
= these late proteins are the structural, capsid proteins
= the progeny virion are assembled from the replicated genetic material & newly made capsid proteins are
then released from the cell

Lysogeny
= the typical replicative cycle described above occurs most of the time when viruses infect cells
= lysogenic cycle, is an alternative pathway use by some viruses in w/c the viral DNA becomes integrated
into the host cell chromosome & no progeny virus particles are produced at that time
= important medical function: is the synthesis of several exotoxins in bacteria
(ex. diphtheria & botulinum toxins, coded for by the genes of the integrated bacteriophage (prophage)
= lysogenic conversion – the term applied to the new properties that a bacterium acquires as a result of
expression of the integrated prophage genes
= Fig 29-4: several aspects of infections by tumor viruses & herpesviruses are similar to the events in the
lysogenic cycle of lambda phage; infection by lambda phage in E. coli begins w/ injection of the
linear, double-stranded DNA genome through the phage tail into the cell; the linear DNA
circularizes (circularization is important bec it is the circular form that integrates into the host cell
DNA); and then viral DNA integrates into the cell DNA; the integration occurs by the matching
of a specific attachment site on the lambda DNA to a homologous site on the E. coli DNA & the
integration (breakage & rejoining) of the 2 DNAs mediated by a phage-encoded recombination
enzyme; the integrated viral DNA is called a prophage

GENETICS & GENE THERAPY

@ The study of viral genetics falls into 2 general areas:

1. mutation & their effect on replication & pathogenesis
2. the interaction of 2 genetically distinct viruses that infect the same cell
@ Viruses serve as vectors in gene therapy & in recombinant vaccines (2 areas that hold great promise for
the treatment of genetic diseases & the prevention of infectious diseases)
Mutations
= mutation is a change in the base sequence of DNA or RNA that usually results in insertion of a
different amino acid into a protein & the appearance of an altered phenotype
= important practical use of mutation is in the production of vaccines containing live, attenuated
virus; these attenuated mutants have lost their pathogenicity but have retained their antigenicity,
so that they induce immunity w/o causing diseases

Interactions
When 2 genetically distinct viruses infect a cell, 3 different phenomena can ensue:
1. Recombination = is the exchange of genes between 2 chromosomes that is based on crossing
over w/in regions of significant base sequence homology

2. Complementation = can occur when one of the 2 viruses that infects the cell has a mutation
that results in a nonfunctional protein
= the nonmutated virus “complements” the mutated one by making a functional protein
that serves for both viruses
= complementation is an important method by which a helper virus permits replication of
a defective virus
= Fig 30-1: If either virus A or virus B infects a cell, no virus is produced because each
has a mutated gene. If both virus A & virus B infect a cell, the protein produce
of gene Y of virus A will complement virus B, the protein produce of gene A of
virus B will complement virus A.

3. Phenotypic mixing = the genome of virus type A can be coated w/ the surface proteins of
virus type B
= this phenotypically mixed virus can infect cells as determined by its type B protein
coat but the Progeny virus from this infection has a type A coat, it is encoded solely by
its type A genetic material
= Fig 30-2: A retrovirus (A) & a rhabdovirus (B) infect the same cell; the progeny
viruses include phenotypically mixed particles (2, 3, 4, & 5) & normal progeny virions (1
& 6).

Gene Therapy & Recombinant Vaccines

Viruses are being used as genetic vectors in 2 ways:
1. to deliver new, functional genes to patients w/ genetic diseases (gene therapy)
= retroviruses are currently being used as vectors of the gene encoding adenine deaminase (ADA) in patienhts
w/ immunodeficiencies resulting from a defective ADA gene

2. to produce new viral vaccines that contain recombinant viruses carrying the genes of several different viruses,
thereby inducing immunity to several diseases w/ one immunization
= recombinant viral vaccines contain viruses that have been genetically engineered to carry the genes of other
viruses
= ex. the gene for the surface antigen of hepatitis B virus has been introduced into vaccinia virus & is
expressed in infected cells

CLASSIFICATION OF MEDICALLY IMPORTANT VIRUSES

= the classification of viruses is based on chemical & morphologic criteria

= 2 major components of the virus used in classification are:
1. the nucleic acid (its molecular weight & structure)
2. the capsid (its size & symmetry & whether it is enveloped)

I. Based on Tissues predilection

1. Pneumotrophic viruses – viruses affecting the respiratory tract
Ex. Influenza virus, Adenovirus, Rhinovirus
2. Dermothrophic viruses – those affecting the skin
Ex. Verruca virus (causing wart)
3. Neurotrophic viruses – those affecting the nervous system
Ex. Rabies virus, Poliovirus
 4. Viscerotrophic viruses – those affecting the visceral organs
Ex. Hepatitis virus, yellow fever virus

II. Based on Nucleic Acid Type

A. DNA Containing Viruses

1. Parvoviruses = very tiny naked icosahedral viruses w/c multiply in the nucleus of infected cells; they
are only single stranded DNA virus
Ex. Adeno-associated virus (AAV) = multiply only in the simultaneously infected w/
Adenoviruses

2. Papoviruses = naked icosahedral tumor inducing viruses

= 2 genera:
i. Genus Papillomavirus
Ex. Human papilloma virus – causing varrucae vulgaris or warts
ii. Genus Polyomavirus
Ex. BK virus – isolated from urine of renal transplant patients
JC virus – isolated from brain of patients w/ progressive
multifocal leucoencephalopathy (PML)

3. Adenoviruses = naked icosahedral double stranded DNA viruses

Ex. i. Human adenoviruses – agents of respiratory disease of the “cold variety”
ii. Enteric adenoviruses – causing enteritis-associated enteric infections

4. Hepadnavirus
Ex. Hepatitis B virus – is the human pathogen in this family

5. Herpesvirus = enveloped icosahedral viruses; they are highly cytopathic in cultured cells & frequently
establish latent infections in sensory ganglia for indefinite periods of time & then reactive
Ex: i. Herpes simplex virus type I – commonly termed as the “oral” strain, producing
infections above the waist; stomatitis, fever blisters, upper respiratory
infections, severe & generally fatal encephalitis
​ ii. Herpes simplex virus type II – commonly termed as the “genital” strain causing
​ genital infections
iii. Varicella-zoster virus – man is the only known natural host
- the name of the virus reflects 2 diesases:
a. Varicella or chicken pox – the result of the primary infection
b. Zoster or shingles – the result of the reactivation of varicella virus
present in latent from in the sensory ganglia
 iv. B virus – causing fatal encephalitis in humans
v. Cytomegalovirus – most common cause of congenital infections in humans; can
​ also cause jaundice, brain damage & death
vi. EB virus or Epstein-Barr virus – causative agent of infectious Mononucleosis or
​ “Kissing’s Disease”; also associated w/ Burkitt’s lymphoma &
​ nasopharyngeal carcinoma

6. Poxviruses = largest & most complex of all viruses

= characteristically brick-shaped
= multiply in the cytoplasm
Ex. i. Variola major – causing small pox
ii. Variola minor – causing alastrim
iii. Cowpox – causing vesicular eruptions of the skin in humans
iv. Erf virus – a poxvirus of sheep that can also affect humans, producing nodules on
​ hands
v. Molluseum contagiosum – affecting only humans causing benign epidermal
​ tumors
vi. Yaba Monkey tumor virus – affecting monkeys & humans causing benign
​ subcutaneous tumors

7. Iridoviruses = icosahedral cytoplasmic deoxyviruses w/c are mostly insect viruses

B. RNA Containing Viruses

1. Picornaviruses = naked icosahedral viruses; the name “picorna” is derived from pico (small)
 a. Genus Enteroviruses – very tiny viruses found in the intestines of man & other animals;
stable at ph 3
Ex. i. Poliovirus – causing poliomeylitis
ii. Coxsackievirus A & B – causing aseptic meningitis; these 2 groups are
​ differentiate on the basis of selective tissue damage:
​ > Coxsackievirus A – produce extensive myositis of the skeletal muscles
​ w/ flaccid paralysis
> Coxsackievirus B – produce focal muscle lesions, necrosis of the fat pads
& spastic paralysis
iii. ECHO virus (enteric Cytopathogenic Human Orphan) – causing paralysis,
​ diarrhea, aseptic meningitis
iv. Human enterovirus 72 or Hepatitis A virus – causing infections hepatitis or
​ Hepatitis A
b. Genus Cardiovirus
Ex. Encephalomyocarditis virus (EMC) – causing mild febrile illness
c. Genus Rhinovirus
Ex. Human rhinovirus – causing common colds, bronchitis, bronchopneumonia
d. Genus Aphthovirus
Ex. Foot & mouth disease virus

2. Calicivirus = naked icosahedral viruses

Ex. 2 human pathogens: i. Norwalk virus – causing gastroenteritis
ii. Hepatitis E virus

3. Reoviruses = REO stands for “respiratory-enteric orphan” (so called because they were originally
found in the respiratory & enteric tracts & were not associated w/ any human disase); naked
nucleocapsid possess 2 capsid shells & double-stranded DNA
⮚ Genus Orthorevirus – Mammalian reviruses

⮚ Genus Orbivirus – Colorado Tick fever – causing encephalitis in man

⮚ Genus Cypovirus

⮚ Genus Phytoreovirus & Genus Fijivirus – plant viruses

⮚ Genus Rotavirus – Human rotavirus – causing diarrhea in infants

4. Flaviviruses = include yellow fever virus, dengue virus, & St. Louis & Japanese encephalitis viruses

5. Togaviruses = enveloped icosahedral viruses include many of the viruses previously known as
arboviruses (arthropod borne); they multiply in bloodsucking insects as well as vertebrates;
rarely producing disease in either
⮚ ** Genus alphavirus (mosquito-borne) – causing encephalitis in man
- Eastern, Western & Venezuelan Equine Encephalitis – causing encephalitis in man
- Chikungunya – causing myositis & arthritis
- O’Nyong-Nyong – causing fever, arthralgia, rash
⮚ Genus Flavivirus
- yellow fever virus – causing hemorrhagic fever, hepatitis, etc.
- Dengue virus – causing fever, arthralgia, rash
- Japanese encephalitis -- causing fatal encephalitis
⮚ ** Genus Rubivirus – causing German measles (Rubella virus) & severe deformities of
fetuses in the 1st trimester of pregnancy
⮚ Genus Pestivirus
- Hog cholera virus
** are human pathogens

6. Retroviruses = (RNA tumor viruses) – envelope particles containing a coiled nucleocapsid w/an
icosahedral core shell; all members possess the unique enzyme known as “reverse transcriptase”
 that’s why its named ‘retro’
= 3 medically important groups:
a. Oncovirus group – w/c contains the sarcoma & leukemia viruses
Ex. human T-cell leukemia (HTLV)
b. Lentivirus group – “slow virus” group w/c includes human immunodeficiency virus
(HIV)
c. Spumaviruses – comprises the foamy virus
= in cell cultures (esp kidney), it causes the formation of multinucleated vacuolated giant cells that have a
highly characteristic appearance

7. Orthomyxoviruses = the term ‘myxo” refers to the affinity of these viruses for mucins, & “ortho” is
added to distinguish them from the paramyxoviruses
= possess 2 glycoprotein spikes: a. hemagglutinin
b. neuraminidase
Ex. Influenze virus – main human pathogen; causing acute respiratory disease

8. Paramyxoviruses = they differ from orthomyxoviruses in that their genomes are not segmented & their
hemagglutinin & neuraminidase are located on the same glycoprotein spike
= sometimes referred to as hemadsorption viruses because their presence were recognized by the
hemadsorption of guinea pig red cells to tissue culture sheet
= important human pathogens: measles, mumps, parainfluenza & respiratory syncytial viruses
(RSV)

9. Rhabdoviruses = are bullet-shaped enveloped viruses w/ a helical nucleocapsid & a single-stranded,

linear, nonsegmented, negative-polarity RNA
= the term “rhabdo” refers to the bullet shape
Ex. rabies virus – is the only important human pathogen
- causing rabies (acute infectious disease of CNS that is almost always fatal)

10. Filoviruses = highly pleomorphic; the term “filo” refers to the long filaments (long filaments that are
80 nm in diameter but can be thousands of nanometers long)
= 2 human pathogens: a. Ebola virus – causing acute hemorrhagic fever
b. Marburg virus – causing fatal hemorrhagic fever

11. Coronaviruses = the term “corona” refers to their characteristic large club-shaped spikes protruding
from the envelope w/c gives them a crown like appearance
= cause respiratory tract infections in human (ex. common cold)
Ex. Human infectious bronchitis virus – causing acute upper respiratory diseases

12. Arenaviruses = the term “arena” (a Latin word) w/c means “sandy” that refers to granules on the virion
surface that are nonfunctional ribosomes
= 2 human pathogens: a. lymphocytic choriomeningitis virus
b. Lassa fever virus

13. Bunyaviruses = the term “bunya” refers to the prototype

= Bunyamwera virus, w/c is named for the place in Africa where it was isolated
Ex. viruses cause encephalitis & various fevers such as Korean hemorrhagic fever

PATHOGENESIS

The ability of viruses to cause disease can be viewed on 2 distinct levels:

1. the changes that occur within individual cells &
2. the process that takes place in the infected patient

The Infected Cell

@ 4 main effects of virus infection on the cell:
1. death
= inhibition of host cell protein synthesis frequently occurs first & is the most important
= inhibition of DNA & RNA synthesis may be a secondary effect
 = NOTE: synthesis of cellular proteins is inhibited but viral protein synthesis still occurs
= infected cells contain inclusion bodies (w/c are discrete areas containing viral proteins or viral
particles) – best example: Negri bodies (are eosinophilic cytoplasmic inclusions found in
rabies virus-infected brain neurons)

2. fusion of cells to form multinucleated cells

= multinucleated giant cells are characteristically form after infection w/ herpesviruses &
paramyxoviruses
= fusion occurs as a result of cell membrane changes w/c are probably due to the insertion of viral
proteins into the membrane
= CYTOPATHIC EFFECT (CPE) – hallmark of viral infection of the cell
- refers to the change in appearance of the infected cell
- is the basis for the plaque assay, an important method for
quantifying the amount of virus in a sample

3. malignant transformation
= is characterized by unrestrained growth, prolonged survival, & morphologic changes

4. no apparent morphologic or functional change

= infection of the cell accompanied by virus production can occur w/o morphologic or gross
functional changes
= this highlights the wide variation in the nature of the interaction between the virus & the cell,
ranging from rapid destruction of the cell to a symbiotic relationship in w/c the cell survives &
multiplies despite the replication of the virus
The Infected Patient
@ Pathogenesis in the infected patient involves:
1. transmission of the virus & its entry into the host
= viruses are transmitted to the individual by many different routes:
a. person-to-person = by transfer of respiratory secretions, saliva, blood, or semen & by
fecal contamination of water or food
b. transplacental = between mother & offspring in utero across the placenta at the time of
delivery or during breast feeding
c. animal-to-human transmission = either directly from a bite of a reservoir host as in rabies or
indirectly through the bite of an insect vector, such as mosquito, w/c transfer the virus
frorn an animal reservoir to the person
d. activation of a latent, nonreplicating virus to form an active, replicating virus can occur within the
individual, w/ no transmission from an external source

2. replication of the virus & damage to cells

3. spread of the virus to other cells & organs
= viral infections are either:
a. localized to the portal of entry
- best example is the common cold, w/c involves only the upper respiratory tract; influenza is
localized primarily to the upper & lower respiratory tracts
b. spread systematically
- ex. is poliomyelitis (Fig 32-1: after poliovirus is ingested, it infects the cells of the small intestine
& then spreads to the mesenteric lymph nodes, where it multiplies again; it then enters the
bloodstream & is transmitted to the CNS, where damage to the anterior horn cells occurs, resulting
in the characteristic muscle paralysis; it is during this obligatory viremia that circulating IgG Abs
induced by the polio vaccine can prevent the virus from infecting the CNS; viral replication in the
gastrointestinal tract results in the presence of poliovirus in the feces, thus perpetuating its
transmission to others)

4. the immune response, both as a host defense & as a contributing cause of certain diseases
= viral diseases are the result of cell killing by virus-induced inhibition of macromolecular synthesis; but
there are certain diseases in w/c cell killing by immunologic attack plays an important role in pathogenesis
= Ex. (LCM) lymphocytic choriomeningitis virus is inoculated into the brain of an adult mouse [w/c also
happens in man]; virus replication occurs & death follows; however, when LCM virus is inoculated into
the brain of an immunosuppressed adult mouse or newborn mouse, the animal remains well despite
extensive virus replication; when immune lymphocytes are inoculated into these infected, healthy mice,
death ensues
 = similar case happens in hepatitis B virus infection, in w/c immune complexes play a role in producing
the chronic hepatitis & arthritis characteristic of this disease

5. persistence of the virus in some instances

= the mechanisms that may play a role in the persistence of viruses include:
a. integration of a DNA provirus into host cell DNA
b. immune tolerance – bec neutralizing Abs are not formed
c. formation of virus-Ab complexes which remains infectious
d. location w/in an immunologically sheltered “sanctuary” (ex. brain)
e. rapid antigenic variation
f. spread from cell to cell w/o an extracellular phase – so that virus is not exposed to Ab
g. immunosuppression – as in AIDS

= 3 types of clinically important persistent viral infections :

a. chronic-carrier infections – some patients who have been infected w/ certain viruses continue to
produce significant amounts of the virus for long periods
- the carrier state can either be asymptomatic or becomes symptomatic
- Ex. hepatitis B virus carriers, neonatal rubella virus & CMV ( in which
carriers can produce virus for years)
b. latent infections – the patient recovers from the initial infection & virus production stops;
subsequently, the symptoms may recur, accompanied by the production of virus
- Ex. herpes simplex virus infections
c. slow virus infections – the term “slow virus” refers to the prolonged period between the initial
infection & the onset of disease, w/c is measured in years

HOST DEFENSES

@ Host defenses against viruses fall into 2 major categories:

1. NONSPECIFIC DEFENSES = most important are the interferons w/c are an early, first-line defense
a. interferons – are a heterogenous groups of glycoproteins (molecular wt 20,000-40,000)
produced by human & other animal cells after viral infection or after exposure to other
inducers
- they inhibit the growth of viruses by blocking the translation of viral proteins
- are divided into 3 groups based on the cell of origin
i. leukocyte
ii. fibroblast known as alpha, beta, & gamma interferons
iii. lymphocyte * alpha & beta = are induced by viruses
* gamma = induced by antigens
- Fig. 33-1: induction & action of interferon:
⮚ (A) virus infection induces the synthesis of interferon, w/c then leaves the infected cell

⮚ (B) interferon binds to the surface receptor of an uninfected cell & induces the synthesis of 3 new
enzymes (antiviral proteins)
⮚ (C) antiviral proteins block the translation of viral mRNA

b. phagocytosis – fixed macophages of the reticuloendothelial system & alveolar macrophages are
the important cell types in limiting virus infection; unlike PMN leukocytes are the
predominant cellular defense in bacterial infections

c. fever – inhibits viral replication in 2 ways:

i. higher body temperature may directly inactivate the virus particles (esp enveloped
virus w/c are more heat-sensitive than non-enveloped viruses)
ii. replication of some viruses is reduced at higher temperatures

d. mucocillary clearance – such mechanism of the respiratory tract may protect the host
- if damage (ex. from smoking), results in an increased frequency of viral respiratory
 tract infections esp influenza

e. factors that modify host defenses:

i. age = is a significant variable in the outcome of viral infections
= viral infections are more severe in neonates & in the elderly than in older
children & young adults
ii. increased corticosteroids levels = corticosteroids can cause a variety of pertinent
effects such as lysis of lymphocytes, decreased recruitment of monocytes,
inhibition of interferon production & stabilization of lysosomes

2. SPECIFIC DEFENSES
@ Acquired immunity = the most important type of defense
a. Active immunity = actively acquired by exposure to the virus
= can be elicited by contracting the actual disease by having an inapparent infection or by
being vaccinated
= important in the prevention of disease w/c is chiefly due to the presence of
immunoglobulins
⮚ IgA –confers protection against viruses that enter through the respiratory & gastrointestinal
mucosa
⮚ IgM & IgG – protect against viruses that enter or are spread through the blood
- the lifelong protection against systemic viral infections (ex. childhood diseases: measles,
mumps, rubella, & chickenpos (varicella) is a function of anamnestic (2ndary) response of IgG
= protection by active immunity can be affected by the phenomenon of “original antigenic
sin” (the term refers to the observation that when a person is exposed to a virus that cross-reacts
w/ another virus to which that individual was previously exposed, more Ab may be produce
against the original virus than against the current one; it appears that the immunologic memory
cells can respond to the original antigenic exposure to a greater extent than to the subsequent one –
ex case of influenza virus & severe hemorrhagic dengue fever virus)

= 2 MAIN MECHANISMS HOW Ab INHIBIT VIRUSES:

i. neutralization – neutralizing the infectivity of the virus by Ab binding to the proteins on the
outer surface of the virus
- 2 effects:
> it can prevent the interaction of the virus w/ cell receptors
> stabilize the virus so that uncoating does not occur (Ab-coated virus is more rapidly
phagocytized than normal virus, a process similar to the opsonizing effect of Ab on
bacteria)
ii. lysis of virus-infected cells – in the presence of Ab & complement
= not all virus infections induce Abs; tolerance to viral Ags can occur when the virus infection
develops in a fetus or newborn infant (ex is what happens in lymphocytic choriomeningitis [LCM]
infection in mice

b. Passive immunity = passively acquired by the transfer of immune serum

= the term “passive” refers to the administration of preformed antibodies
= the 3 most frequently used high-titer preparations are used after exposure to :
i. hepatitis B virus
ii. rabies virus
iii. varicella-zoster virus
= low-titer immune globulin is used to prevent hepatitis A in people traveling to areas where this
infection is hyperendemic

LABORATORY DIAGNOSIS

3 Approaches to the diagnosis of viral diseases by the use of clinical specimens:

1. Identification of the virus in cell culture

 = growth of viruses requires cell cultures bec viruses replicate only in living cells not on cell-free media
like most bacteria do
= virus growth frequently produces a characteristic cytopathic effect (CPE) that provide a preliminary
diagnosis
= if the virus does not produce a CPE, its presence can de detected by several other techniques:
a. hemadsorption – attachment of rbc to the surface of virus-infected cells
- limited to viruses w/ a hemagglutinin protein on their envelope such as mumps,
parainfluenza, & influenza viruses
b. interference w/ the formation of a CPE by a 2nd virus
c. decrease in acid production by infected, dying cells – used to detect certain enteroviruses

= a definitive identification of the virus grown in cell culture is made by using known Ab in the ff
tests: > complement fixation
> hemagglutination inhibition
> neutralization
> fluorescent Ab
> radioimmunoassay
> enzymes-linked immunosorbent assay
> immunoelectron microscopy

2. microscopic identification directly in the specimen

= specimens such as biopsy material or skin lesions
= 3 different procedures can be used:
a. light microscopy – reveals characteristic inclusion bodies or multinucleated giant cells
b UV microscopy – used for fluorescent-Ab staining of the virus in infected cells
c. electron microscopy – detects virus particles w/c can be characterized by their size &
morphology

3. serologic procedures to detect a rise in Ab titer or the presence of IgM Ab

ANTIVIRAL DRUGS

⮚ the number of antiviral drugs is very small compared to drugs against bacterial infections (the major
reason for the difference is the difficulty in obtaining selective toxicity against virus & their replication
is involved w/ the normal synthetic processes of the cell)
⮚ limitation:
= are relatively ineffective (bec many cycles of viral replication occur during the incubation period
when the patient is well; by the time the patient has a recognizable systemic viral disease, the virus has
spread throughout the body & it is too late to interdict it)
= emergence of drug-resistant viral mutants

Potential sites for antiviral chemotherapy

Site of Action Effective drugs

Early events (entry or uncoating of the virus) Amantadine
Nucleic acid synthesis by viral DNA & RNA Acyclovir, ganciclovir, vidarabine, vidarabine
polymerase Idoxuridine, trifluridine, azidothymidine, dideoxyinosine,
dideoxycytidine, ribavirin
Other virus-specific enzymes
Protein synthesis directed by viral mRNA
Cleavage of precursor polypeptides
Assembly of the particle, including the matrix
protein
Release of the particle by budding

@ Inhibition of early events:

A. amantadine = used to prevent influenza A infections

= it inhibits uncoating of the virus: absorption & penetration occur normally, but
transcription by the virion RNA polymerase does not
@ Inhibition of viral nucleic acid synthesis:

** Inhibitors of Herpesviruses:

A. acyclovir = is active primarily against herpes simplex virus types 1 & 2 & varicella-zoster
virus
= is due to the virus-encoded thymidine kinase, w/c phosphorylates acyclovir much more
effectively than does the cellular thymidine kinase
= bec only herpes simplex virus & varicella-zoster virus encode a kinase that efficiently
phosphorylates the drug; no activity against cytomegalovirus

B. ganciclovir = active against cytomegalovirus esp retinitis in AIDS & other infections caused
by this virus

C. vidarabine = effective against herpes simplex virus type 1 infections such as encephalitis &
dermatitis but is less effective & much more toxic than acyclovir
= on entering the cell, the drug is phosphorylated by cellular kinases to the triphosphate,
w/c inhibits the herpesvirus-encoded DNA polymerase more effectively than the cellular
DNA polymerase

D. idoxuridine = is clinically useful in the topical treatment of herpes simplex virus

keratoconjunctivitis
= it causes the formation of faulty progeny DNA & mRNA

E. trifluridine = mechanism of action is similar as idoxuridine

** Inhibitors of retroviruses: [the selective toxicity of the ff drugs is based on their ability to
inhibit DNA synthesis by the reverse transcriptase of human immunodeficiency virus
(HIV)]

F. azidothymidine = also inhibits growth of virus in cell culture; is currently the drug of choice in
patients w/ AIDS

G. dideoxyinosine = causes chain termination during DNA synthesis by the reserves transcriptase
of HIV & is used to treat patients who are intolerant of or resistant to AZT

H. dideoxycytidine = same as dideoxyinosine

** Inhibitors of other viruses:

I. ribavirin = inhibits the synthesis of guanine nucleotides, w/c are essential for both DNA &
RNA viruses
= used clinically to treat pneumonitis caused by respiratory syncytial virus in infants &
to treat severe influenza B infections

@ Inhibition of viral protein synthesis:

A. interferon = effective in the treatment of some patients w/ chronic hepatitis B & C infections

B. methisazone = specifically inhibits the protein synthesis of poxviruses, such as smallpox &
vaccinia viruses
= by blocking the translation of late mRNA
 VIRAL VACCINES

@ 2 types of vaccines:
1. live virus -in general, live vaccines are preferred to vaccines containing killed virus bec their
protection is GREATER & LONGER-LASTING
- w/ live vaccines, the virus multiplies in the host, producing a prolonged antigenic
stimulus, & both IgA & IgG are elicited when the vaccine is administered by the natural
route of infection
- booster doses are also recommended esp w/ measles & polio vaccines
- 3 concerns about the use of live vaccines:
a. they are composed of attenuated viral mutants, w/c can revert to virulence either
during vaccine production or in the immunized person
b. live vaccine can be excreted by the immunized person
c. a 2nd virus could contaminated the vaccine if it was present in the cell cultures used to
prepare the vaccine.

2. killed virus - usually given intramuscularly, do not stimulate a major IgA response
- Disadvantages:
> produce a shorter duration of protection
> less protective
> induce fewer IgA Abs
- Advantages:
> they cannot revert to virulence
> are more heat-stable = so can be used more easily in tropical climates

@ Current viral vaccines (1993)

USAGE VACCINE LIVE / KILLED VIRUS

Common Measles Live
Mumps Live
Rubella Live
Polio Both
Influenza Killed
Hepatitis B Killed
Rabies Killed
Special situations Yellow fever Live
Japanese encephatlitis Killed
Adenovirus Live
Smallpox Live

@ Characteristics of live and killed viral vaccines

Characteristic Live Vaccine Killed Vaccine

Duration of immunity Longer Shorter
Effectiveness of protection Greater Lower
Immunoglobulins produced IgA and IgG IgG
Reversion to virulence Possible No
Stability to rm temp Low High
Excretion of virus & transmission to nonimmune Possible No
contacts
Features of viruses that infect the respiratory tract

Virus Disease Lifelong Vaccine Viral

Immunity to Available Latency
Disease
RNA viruses
Influenza A virus influenza no + -
Parainfluenza croup no - -
virus
Respiratory bronchiolitis incomplete - -
syncytial virus
(RSV)
Rubella virus rubella yes + -
Measles virus measles yes + -
Mumps virus parotitis, yes + -
meningitis
Rhinovirus common cold no - -
Coronavirus common cold no - -
Coxasackievirus Herpangina, no - -
pleurodynia
DNA viruses
Herpes simplex gingivostomatitis no - +
virus type 1
Epstein-Barr virus infectious yes - +
mononucleosis
Varicella-zoster chickenpox, yes - +
virus shingles
Adenovirus pharyngitis no +2 +