Download Viral Structure

Microbiology: Introduction to Virology (Pellett)
VIRUSES:
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General:
Infectious, obligate intracellular parasite
Genome consists of DNA or RNA
Metabolically inert on their own (outside the context of a living cell)
Viral genome directs its own replication using cellular systems in a host cell
Virus particles (virions) are formed by assembly from newly synthesized components within the host cell
A progeny virion is the vehicle of transmission of the genome to the next host cell/organism (disassembly
initiates the beginning of the next infectious cycle)
o This disassembly stage is a vulnerable state for the virus
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Properties of a Virus:
Minimal Virus: genome with origin of replication and a coat
o DNA or RNA genome
o Proteinaceous coat: also called a capsid
Nucleocapsid: genome + capsid
Envelope: viruses can be enveloped or not
Virion: a complete virus particle with its DNA or RNA core and protein coat as it exists outside the cell; also called
a viral particle
Translation Parasites: must use cellular ribosomes in a host in order to replicate
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Classification:
Nature of Genetic Material:
o RNA:
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Single or double stranded
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Positive or negative sense (Baltimore system)
 At some point in their replication cycle, all viruses must adopt a form that allows
transcription of mRNA that can be translated by cellular ribosomes
 Requires –ssRNA or dsDNA/dsRNA in order to translate into +mRNA
 Possible Scenarios:
o +ssRNA Virus  –ssRNA  +mRNA
o +ssRNA Virus  –ssDNA  dsDNA  +mRNA
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Non-segmented or segmented
o DNA:
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Single or double stranded
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Linear or circular
Capsid Structure:
o Helical
o Icosahedral
o Complex
Other:
o Gene organization
o Mode of replication
o Susceptibility to physical and chemical agents (for example, chloroform makes enveloped viruses non
infectious)
o Cell tropism (what cells and tissues they infect)
o Pathogenic effects
MAJOR CRITERIA:
o DNA or RNA genome
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RNA Virus Examples: polio virus, influenza virus
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DNA Virus Examples: adenovirus, herpesvirus
o Nature of capside
o Enveloped or non-enveloped (naked)
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Virion Structure:
In general: most viruses smaller than most bacteria
Virion: complete infectious form of the virus particle
o Capsid: encapsulates the genome; in some cases, surrounded by an envelope (derived from host cell
membranes)
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Helical: enveloped
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Icosahedral: enveloped or non-enveloped
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Complex
o Non-Structural Proteins:
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Enzymes
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Host regulators
Individual virus species may share many properties with their relatives, but yet still have readily distinguished
genomes: example of differences between herpesviruses shown via Southern blot
Examples:
o Picornaviruses:
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Small

Non-enveloped

+RNA genome (needs to be transcribed to negative sense)
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Non-segmented: genome encodes single open reading frame that is translated into a large
polypeptide and then proteolytically processed to a set of individually functioning proteins
o Influenza Viruses:
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Enveloped

-RNA genome
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Segmented: each gene encoded on individual chromosomes; basis for reassorment (new
strains of virus emerge from infections with 2 different strains)
o Adenovirus:

Non-enveloped

dsDNA genome

Transcribed by cellular RNA polymerase II (studying this virus led to discovery of mRNA
splicing)
o Herpesvirus:

Enveloped

Tegument: layers of proteins between envelope and capsid
 Important in helping the virus control the cell following infection

dsDNA genome (may encode for as many as 200 genes; tightly controlled expression)
Properties of Lytic Infections:
Lytic Infection: making new infectious virions; can be initiated by a single virion
o Eclipse Period: interval between disassembly of input virion and production of new infectious progeny
o Burst Size: number of infectious virions released per infected cell (100s-1000s)
o Time Scale: can be hours or days from time of infection to lytic burst
Steps:
o Entry: attachment to receptor, penetration and uncoating

Mechanisms:
 Endocytosis (poliovirus, influenza virus, adenovirus)
 Genome injection (poliovirus)
 Fusion at cell membrane (HIV, vaccinia virus, herpesvirus)
o Gene Expression:

mRNA synthesis

Protein translation
o Genome replication

Sites:
 Cytoplasm: most RNA viruses + poxviruses
 Nucleus: most DNA viruses + orthomyxoviruses
 Both: retroviruses, hepadnaviruses
o Assembly/packaging
o Egress/release

Mechanisms:
 Cell lysis (poliovirus, adenovirus)
 Budding from cytoplasmic membrane (influenza, HIV)
 Cell associated (vaccinia virus)
 Vesicle fusion (herpes virus)
Consequences of Infection:
Transformation:
o Immortalization
-
o Serum independent cell replication
o Loss of contact inhibition
o Ability to form tumors
Cytopathic Effect (CPE):
o Rounding (lose defined shaped)
o Fusion (syncytia formation- giant infected cell)
o Intracellular vacuoles and inclusion bodies
o Lysis
o Cell death
Introduction to Virology II: Pathogenesis

General:
Most result in asymptomatic (subclinical) infections
Same disease may be caused by a variety of different viruses
Same virus may cause a variety of diseases
Outcome of infection determined by the interaction of the virus and the host
o Virus strain
o Route of infection
o Infectious dose
o Host immune status
o Host genetics
o Virus cytotoxicity
o Immunopathology
o Host health
o Co-infections
Local vs. systemic infections
Seasonality
Various incubation periods: time to disease

Principles of Viral Infections:
Modes of Transmission and Host Entry:
o Person-to-person transmission: some paths more likely if illness present; others if relatively healthy
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Fecal-oral
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Respiratory
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Animal bite
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Arthropods
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Sexual
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Bloodborne
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Vertically (transplacental, genetic)
o Virus can enter and egress from the same or different routes: some also use multiple paths
o Defenses at portals of entry: keratinized skin, mucosa
Sites of Primary Replication
Modes of Intrahost Spread: via blood, lymphatic ducts, or neurons (cell-free or cell-associated)
Sites of Secondary Infection
Organs and Tissues Affected
Host Responses:
Clearance vs. Persistence:
o Latent State:
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Cellular: no infectious particles produced; can be reactivated to lytic state
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Organismal: period between infection and disease
o Persistent Infection:

Cellular: lytic state, equilibrium between cell death and production (but still making virus
paticles)

Organismal: continuous inhabitation of the host
o Abortive Infection: non-productive, not reactivation
Patterns of Viral Infection:
o Acute: GI viruses
o Latent: HSV (reactivations occur)
o Progressive: HIV or hep C
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o Chronic or Persistent: HIV or hep C
o Failure to clear all evidence of infection: polio and measles
o Subclinical/asymptomatic: ~50% of HSV transmission is during asymptomatic periods
o Slow: long-term persistence prior to onset of disease (HPV and cervical cancer)
Viral Pathogenesis:
Genes groups based on contribution to virulence:
o Basic Replication Functions: viral RNA polymerase
o Immunevasion: proteins that downregulate Ag presentation
o Cell and tissue tropism: HIV uses CD4 as cellular receptor
o Toxic products: rotavirus NSP4 induces diarrhea
Viral load matters: the larger the load, the higher the probability of disease
Viruses and Cancer: generally unintended by-products of niche-management by the virus
o HPV and cervical cancer
o HTLV-1 and T cell leukemia
o HHV-8 and Kaposi’s sarcoma
o EBV and Burkitt’s Lymphoma and nasopharyngeal carcinoma
o Hep B/Hep C and liver cancer
Host Responses:
Innate immunity:
o Physical barriers: skin, mucosa, respiratory filters
o Intracellular defenses: IFN (and other cytokines), PKR, RNase, stress responses, cell-death (apoptosis,
necrosis, autophagy)
o NK cells, macrophages and neutrophils
Acquired immunity:
o Antibodies and complement

Abs against virions: neutralization
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Abs against viral proteins on cell surfaces: neutralization, inhibition of viral replication,
inhibition of virus release, infected cell lysis and clearance, inhibition of cell-cell transmission
o T cells
Immunopathology:
o Systemic responses to IFN
o Inflammation
o Immune complexes
o Immunocytopathology
ESSENTIALLY EVERY DEFENSE CAN BE BLOCKED OR CIRCUMVENTED BY A VIRUS
Immune Evasion:
All viruses do it (especially large DNA viruses)
Many viral immunomodulatory genes are host-derived
Targets for immune evasion:
o Innate Defenses:
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Apoptosis
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IFN responses
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PKR pathway (proten kinase RNA-activated pathway): activated by dsRNA, which is
uncommon outside of a virus infection and net result is translational arrest (under normal
conditions); the virus can employ mechanisms to inhibit this pathway (allowing translation to
occur)
o Adaptive Responses:
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Ag prensetation
Laboratory Diagnosis of Viral Infections:
Detect the Agent:
o Cytology
o Electron microscopy
o Direct fluorescent Ab (DFA)
o Cell culture
o Nucleic Acids (PCR)
Detect Response to the Agent:
o Serotology (look for Abs against the agent)
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Antivirals:
Must selectively inhibit viral functions without damaging the host
o Targets: every step in replication cycle is potential target
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Attachment and entry (fusion inhibitors)
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Uncoating (ion channel blockers)
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Genome replication (polymerase inhibitors)
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Protein synthesis/assembly and maturation (protease inhibitors)

Egress and release (neuraminidase inhibitors)
Relatively ineffective clinically as compared to bacterial agents
o Why? Many rounds of viral replication has occurred during the incubation period before symptoms
develop
Vaccination is most important to prevent infection
Key Issues:
o Specificity
o Toxicity
o Rapid diagnosis
o Therapeutic threshold
o Resistance