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General Characteristics of Viruses  RNA

 contain single-stranded RNA (except for reoviruses, rotaviruses,


NATURE OF HUMAN VIRUSES coltiviruses, orthoreoviruses, and orbiviruses).
 are enveloped (except for caliciviruses, picornaviruses, and
 Virion: reoviruses).
 the entire virus particles  Have helical capsids (except for picornaviruses, reoviruses, and
 composed of either RNA or DNA togaviruses).
 are obligate intracellular parasites  are classified positive, negative, or ambisense, depending on the
 cannot be observed with a light microscope ability of virion RNA to act as messenger RNA (mRNA).
 replicate in the cytoplasm (except for orthomyxoviruses and
 Genome: retroviruses, which have both a cytoplasmic and a nuclear phase).
 may be single stranded or double stranded, linear or circular, and
segmented or nonsegmented.
 characteristics are used as one criterion for viral classification VIRAL REPLICATION AND GENETICS
that are associated with Viral-specific enzymes and other proteins
within the virion.  General characteristics of viral replication

 Capsid: Replication:
 the protein coat of a viral genome of RNA or DNA  Only occurs only in living cells
 Classified as:  may lead to the death of the host cell (virulent viruses) or may
1. Helical occur without apparent damage to the host cell (moderate
o Protomers not grouped in capsomeres viruses)
o Bound together to form a ribbon which folds
2. Icosahedral 1. Attachment
o a geometric shape with 20 triangular sides o involves the interaction of viral attachment proteins (VAPs) and
o 12 corners with penton specific host-cell receptor sites.
3. Complex o plays an importantrole in viral pathogenesis, determining viral cell
 Functions: tropism.
a) Protects the viral genome. o may be inhibited by antibodies (neutralizing antibodies) against
b) Is the site of receptors necessary for naked viruses to initiate viral receptors or cellular receptor sites.
infection. 2. Penetration
c) Stimulates antibody production. o can occur by a cellular mechanism
d) Is the site of antigenic determinants important in some o Receptor-mediated endocytosis – a cellular mechanism that is
serologic tests. reffered to viropexis when viruses are involved.
 Capsomers: structural units of capsid that are aggregates of viral- o The virus envelope may fuse with the plasma membrane of the
specific polypeptides. host cell.
3. Uncoating
 Nucleocapsid o the separation of the capsid from the viral genome.
 refers to the capsid and enclosed viral genome and is identical to o results in the loss of virion infectivity.
the virion in naked viruses. 4. Budding
o the process by which enveloped viruses obtain their envelope
 Envelope: o it confers infectivity to enveloped viruses.
 phospholipid labile membrane surrounding the the nucleocapsid o preceded by the insertion of virus-specific glycoproteins into the
 masks the shape of the virion membranes of the host cell.
 are from host origin but contain virus-encoded protein o occurs most frequently at the plasma membrane, but also occurs
 Composition: at other membranes.
a) viralspecific glycoproteins
b) host-cell-derived lipids and lipoproteins  Replication in DNA
 Fuctions:
a) contains molecules that are necessary for enveloped viruses 1. Transcription
to initiate infection o occurs in the host-cell nucleus (except for poxviruses) and
b) act as a stimulus for antibody production o regulated by host-cell DNA-dependent RNA polymerases (except
c) serve as antigens in serologic tests for virion-associated RNA polymerase of poxviruses).
d) forms the basis of ether sensitivity of a virus o occurs in a specific temporal pattern, such as immediate early,
 viruses with envelope are more susceptible to inactivation by high delayed early, and late mRNA transcription.
temperature, extreme pH, and chemicals. o may be followed by posttranscriptional processing of primary
 Enveloped viruses are variably shaped or pleomorphic. mRNA transcripts (late adenovirus transcripts).
 Poxvirus are the largest viruses (250 × 350 nm) 2. Translation
 Poliovirus smallest human virus (25 nm) o occurs on cytoplasmic polysomes
o followed by transport of newly synthesized proteins to the
nucleus (except for poxviruses).
3. Genome replication
VIRAL CLASSIFICATION
o occurs after the synthesis of the early proteins.
 Classification: based on chemical and physical properties of
o is semiconservative and is performed by a DNA-dependent DNA
virions. Major families to Genera (physiochemical/serologic)
polymerase, which may be supplied by the host cell
(adenoviruses) or may be virus specific (herpesviruses).
 DNA
4. Assembly
 glycosylated and methylated (Cytosine, Uracil, Thymine) o takes place in the nucleus (except for poxviruses).
 unique purine and/or pyrimidine bases o is frequently an inefficient process that leads to accumulation of
 bound protein molecules viral proteins that may participate in the formation of inclusion
 contain double-stranded DNA (except for parvoviruses) bodies (focal accumulations of virions or viral gene products).
 are naked viruses (except for herpesviruses, poxviruses, and
hepadnaviruses).
 have icosahedral capsids and replicate in the nucleus (except for
poxviruses).
 Replication in RNA 2. Asymptomatic viral disease:
o may also be called subclinical infection because no clinical
1. The viral genome may be single stranded or double stranded and symptoms are evident.
segmented or nonsegmented. o It occurs with most viral infections and can stimulate humoral and
a. It may have messenger (positive-sense) polarity if it is single cellular immunity.
stranded and able to act as mRNA (picornaviruses and 3. Clinical viral disease:
retroviruses). o results from direct or indirect viral effects (e.g., viral-induced
b. It may have antimessenger (negative-sense) polarity if it is cytolysis, immunologic attack on infected cells),
single stranded and complementary to mRNA o lead to physiologic changes in infected tissues.
(orthomyxoviruses and paramyxoviruses). o It is associated with a particular target organ for a specific virus.
c. It is ambisense if it is single stranded with portions of a) Disease does not always follow infection and therefore is
messenger polarity and antimessenger polarity not an accurate index of viral infection; it occurs much less
(arenaviruses). often than inapparent infection.
2. Transcription b) It frequently depends on the size of the viral inoculum.
o involves a viral-specified RNA-dependent RNA polymerase for all
viruses (except retroviruses that use a host-cell, DNA-dependent  Viral aspects of pathogenesis
RNA polymerase)
o Negative-sense viruses use a virion-associated enzyme 1. Viral attachment proteins (VAPs)
(transcriptase). o interact with cellular receptor sites to initiate infection.
3. Translation a) VAPs may react with specific antibodies (neutralizing
o occurs on cytoplasmic polysomes. It may result in the synthesis of antibodies) and become incapable of interaction with
a large polyprotein that is subsequently cleaved (in cellular receptor sites.
posttranslational processing) into individual viral polypeptides b) pH, enzymes, and other host biochemical factors can
(picornaviruses and retroviruses). inactivate VAPs.
4. Genome replication 2. Viral virulence
o occurs in the cytoplasm (except for orthomyxoviruses and o refers to the ability of a particular viral strain to cause disease.
retroviruses) and is performed by a viral specific replicase enzyme o It is a composite of all the factors that allow a virus to overcome
(except for retroviruses). host defense mechanisms and damage its target organ.
o a replicative intermediate RNA structure is required for all single- a) Virulence is genetically determined.
stranded RNA genomes. b) It is decreased with attenuated strains of virus.
o RNA viruses have a higher mutation rate than DNA viruses.
 Cellular aspects of pathogenesis
 Genetics
1. Cellular receptor sites
1. Phenotypic mixing o interact with VAPs to initiate infection.
o results when surface antigens from two related viruses enclose o help determine cell tropism of viruses.
the genome of one of the viruses. o Presence or absence of particular sites may be determined by the
2. Phenotypic masking (transcapsidation) differentiation stage of a cell.
o occurs when pairs or related viruses infect the same cell. 2. Cell tropism
o It results when the genome of one virus is surrounded by the o refers to the propensity of a virus to infect and replicate in a cell.
capsid or capsid and envelope of the other virus. o Tropism is largely determined by the interaction of virus
3. Complementation attachment proteins and cellular receptor sites and the cell’s
o can occur when two mutants of the same virus or, less frequently, ability to provide other components (e.g., substrates and
two mutants of different large DNA viruses infect the same cell. enzymes) essential for viral replication.
o It results when one mutant virus supplies an enzyme or factor 3. Target organ
that the other mutant lacks. o is the organ responsible for the major clinical signs of a viral
4. Genetic reassortment infection and is largely determined by viral virulence and cell
o can occur when two strains of a segmented RNA virus infect a cell. tropism.
o It results in a stable change in the viral genome. 4. Cellular responses to viral infection
5. Viral vectors o result in clinical disease.
o can be constructed with recombinant DNA technology and allow o These responses may be inapparent or may include:
gene transfer into cells. a) Cytopathic effects
o have been used as an approach to treat diseases, particularly b) Cytolysis
monogenic disorders and some cancers c) Inclusion body formation
o are being studied as agents to immunize against other infectious d) Chromosomal aberrations
agents. e) Transformation
f) Interferon (IFN) synthesis
5. Cytopathogenic effects
VIRAL PATHOGENESIS o include inhibition of host-cell macromolecular biosynthesis,
alterations of the plasma membrane and lysosomes, and
 General characteristics development of inclusion bodies.
a) Infectious virus progeny may not be produced.
Viral pathogenesis b) Effects may aid in identification of certain viruses.
o the process of disease production following infection.
o It may lead to clinical or subclinical (asymptomatic) disease.  Types of infections

1. Viral entry into a host: 1. Inapparent infections


o Viruses enter the host most often through the mucosa of the o occur when too few cells are infected to cause clinical symptoms.
respiratory tract but may also enter through the mucosa of the o are synonymous with subclinical disease.
gastrointestinal or genitourinary tract. a) Sufficient antibody stimulation can cause immunity from further
o Entry can be accomplished by direct virus injection into the infections.
bloodstream via a needle or an insect bite. b) They frequently occur when the virus inoculum is small.
2. Acute infections  Inclusion Bodies
o occur when clinical manifestations of disease are observed for a
short time (days to weeks) after a short incubation period. Virus Inclusion Staining Inclusion Name
a) Recovery is associated with elimination of the virus from the Site Properties
body. Adenovirus Nucleus B —
b) Acute infections are classified as localized or disseminated, Cytomegalovirus Nucleus B Owl’s eye
depending on whether the virus has traveled from its site of Herpes simplex Nucleus A Cowdry type A
implantation to its target organ. virus
c) Persistent or latent infections may follow acute infection. Measles virus Both A —
3. Persistent infections Poxvirus Cytoplasm A Guarnieri bodies
o are associated with the continuing presence of the infectious virus (smallpox)
in the body for an extended. Molluscum bodies
a) Clinical symptoms may or may not be present. (molluscum
b) Persistently infected individuals are known as carriers. contagiosum)
c) Constant viral antigenic stimulation leads to high antibody titers Rabies virus Cytoplasm A Negri body
for some antigens. Reovirus Cytoplasm A —
4. Latent infections
Rubella virus Cytoplasm A —
o occur when the infecting virus persists in the body in a
noninfectious form that can periodically reactivate to an
 Patterns of viral disease
infectious virus and produce clinical disease
o are synonymous with recurrent disease.
a) An antibody stimulus is produced only during the initial (primary)
infection and during recurrent episodes.
b) Subclinical reactivations may occur.
c) Latent infections are difficult to detect in cells because viral
antigen production is not detected and cytopathology is not
observed during “silent” periods.
5. Slow infections
o have a prolonged incubation period lasting months/years.
a) These infections do not cause clinical symptoms during incubation
but can produce some infectious agents.
b) They are most often associated with chronic, progressive, fatal
viral diseases of the central nervous system (CNS), such as kuru
and Creutzfeldt-Jakob disease

 Patterns of Acute disease

1. Localized disease
o occurs when viral multiplication and cell damage remain localized
to the site of viral entry into the body.
a) Localized disease has a short incubation time and may cause
systemic clinical features (e.g., fever).
b) Pronounced viremia (virions in the blood) does not usually occur.
c) Sites include the respiratory tract (influenza, rhinovirus);
alimentary tract (picornaviruses, rotaviruses); genitourinary tract
(papillomavirus); and the eye (adenovirus).
d) Disease can spread over the surface of the body to other areas
where it causes another localized infection (picornavirus-induced
conjunctivitis).
e) The immune response that is induced is much weaker than the
response induced by disseminated infections.

2. Disseminated infections
o involve the spread of virus from its entry site to a target organ.
o involve a primary viremia and perhaps a secondary viremia.
a) Incubation time is moderate (e.g., weeks), allowing more time for
the host’s immune system
b) to eliminate the viral infection.
c) The main clinical symptoms are associated with infection of one
target organ, although infection of other organs may be involved.
d) A substantial immune response is generated that frequently
confers lifelong immunity to the host.
e) Viral dissemination is a major feature of disseminated infections.
(1) Viruses may travel in other cells (red blood cells and
mononuclear peripheral white blood cells), the plasma,
extracellular spaces, and nerve fibers.
(2) Viruses can be prevented from disseminating by viral-specific
cytotoxic cells and neutralizing antibodies.

3. Congenital infections are viral infections of a fetus and are caused by


maternal viremia.
a) These infections may lead to maldeveloped organs.
b) They are serious because of the immaturity of the fetal immune
system, the placental barrier to maternal immunity, and the
undifferentiated state and rapid multiplication of fetal cells.
- Katrina Lotho (PandaMT13)

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