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Viral Pathogenesis
Chapter 12
35
Biology
Professional
02/16/2012

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Term
What are the basic stages of viral pathogenesis?
Definition
1) Entry
2) Primary replication
3) Spread (bloodstream/nervous system)
4) Secondary replication (liver/spleen)
5) Spread to target organs
Term
How does Coronavirus (SARS) gain access to the body?
Definition
Alimentary tract; Fecal-Oral

Example of localized acquisition, whether the virus stays where it infects.
Term
Provide an example of localized and system Alimentary tract acquisition of a virus.
Definition
Fecal-Oral spread

Local= Corona virus (SARS)

Systemic= **Enterovirus**, Reovirus, Adenovirus
Term
Provide an example of upper-localized, lower-localized and systemic Respiratory tract acquisition of a virus.
Definition
Upper-locaized= Rhinovirus and **Influenza**

Lower-localized= RSV and **Influenza**

Systemic= Measles and VZV (chicken pox)
Term
Provide an example of localized and systemic Urogenital tract (Sexual) acquisition of a virus.
Definition
Localized= HPV

Systemic= **HIV** and HBV
Term
Provide an example of systemic Eye acquisition of a virus.
Definition
**Enterovirus**, Adenovirus
Term
Which viruses are acquired through contact with an insect vector or animal bite?
Definition
1) Rabies (nonsegmented, ssRNA (-))
2) Bunyavirus (segmented, ssRNA (-))- Hantavirus
3) Togavirus (enveloped, ssRNA (+))- Rubella
4) Flavivirus (enveloped, ssRNA (+))- West Nile/ Dengue
Term
Where are each of the following viruses restricted to:

1) Rhinovirus

2) Parainfluenza

3) Influenza
Definition
1) Upper respiratory tract

2) everywhere

3) everywhere, but more in bronchial
Term
What are 3 factors that affect dissemination?
Definition
1) Portal of entry

2) Host immunity

3) Cell-specific virus receptors
Term
Explain how viral tropism is determined in HIV-1, Influenza and Poliovirus.
Definition
1) HIV-1 binds CDR (receptor) and CCR5/CXCR4 (co-receptor)

2) Influenza binds sialic acid (recptor) and CLRs (co-receptors)

3) Poliovirus binds Pvr (receptor)
Term
What are 4 types of cell dysfunction/morphology change that can occur upon viral infection?
Definition
1) Hyperplasia (HPV warts)

2) Mucous secretion (colds from rhino- and coronaviruses)

3) SYNCITIA (multi-nucleated giant cells in HSV)

4) Inclusion body formation
Term
What viruses can cause cancerous transformation?
Definition
1) HTLV-1

2) EBV

3) HPV-16/18
Term
Which viruses can be diagnosed with a Plaque assay?
Definition
Measures virus titer an involves cellular lysis.

1) HSV
2) Adenovirus
Term
Which viruses can be diagnosed with a focus forming assay?
Definition
Retroviruses
Term
What are cytopathic effects that could be detected by CPE?
Definition
Rounding of cells and Syncytia formation
Term
How can you detect virus particles or virion components in a sample?
Definition
1) light microscope of morphology
2) IF for viral antigens
3) EM for viral particles
4) Hemmaglutination assay for RBC lysis
5) ELISA (indirect)
Term
How can you detect antibodies made against viruses that circulate in the serum (Serology)?
Definition
1) ELISA for antibodies against viral antigens

2) Virus neutralization
Term
What does the IgM:IgG ratio tell you about a viral life cycle?
Definition
- Early IgG response indicates that the viral antigens have been seen before

- A higher ratio means that it is likely a secondary response
Term
Which viruses involve acute infection followed by death of host?
Definition
1) Ebola
2) Hantavirus (Bunyavirus)
Term
Which viruses involve acute infection followed by clearance?
Definition
1) Rhinovirus

2) Rotavirus

3) Influenza
Term
Which viruses involve persistent chronic infections?
Definition
HepB, C and HIV
Term
Which viruses involve later infections and reactivation?
Definition
1) HIV
2) HSV
3) VZV (chicken pox and shingles)
4) EBV
Term
Explain the molecular life cycle of a Enterovirus infection (Picornavirus family).
Definition
Small, unenveloped, ssRNA (+) virus spread by oral-fecal route.

1) Binds to Poliovirus receptor (Pvr)

2) Endocytosis with conformational changes in VP1 and VP4 resulting in fusion.

3) Uncoating at low pH in endosome causes release of ssRNA

4) Replication in cytoplasm, assembly and egression.
Term
What virulence factors are associated with Enterovirus?
Definition
1) CNS spreading

2) Survival in acidic environment (stomach)

3) 2A protein inhibits eIF4G and protein translation

4) 2BC/3A proteins inhibit cell secretory pathway (IL-6 ect)

5) 3C protease cleaves Tbp subunit of TFIId, so not TATA-binding can take place.
Term
How does an Enterovirus spread?
Definition
1) Enters GI (fecal:oral) and spreads to LN in small intestine

2) Primary Replication in LN leads to fever, GI symptoms (90% asymptomatic but STILL infectious)

3) Spread through blood to liver/spleen (1% to CNS b/c of antibody response)

4) If it gets to the brain, it can cause Meningitis (fever, headache, over in 2 weeks) and Paralytic poliomyelitis (acute, flacid paralysis)
Term
How would you diagnose a case of Poliomyelitis?
Definition
Remember, this is very rare (1/20,000) in a Enterovirus infection that has spread to the CNS.

Tissue culture from stool sample and CSF
Term
What is the difference between the Salk and Sabin Polio vaccines?
Definition
Salk- IPV that treats CNS but not GI

Sabin- OPV that also takes care of gut.
Term
What is Pleconaril used for?
Definition
Antiviral drug used against enteroviruses and other picornaviruses such as Polio.
Term
Explain how latent/chronic viral infections occur.
Definition
Example is HIV, with Wedge-shaped nucleocapsid core containing 5-10 copies of RT and IN

1) During latency, NO infectious virus is produced

2) Can undergo reactivation in response to stress, cellular injury or cell-type permissive for replication
Term
How is HIV an example of a latent/chronic viral infection?
Definition
Background- Wedge-shaped nucleocapsid core containing 5-10 copies of RT and IN

- Virion-associated RT converts linear ssRNA to circular dsDNA, which is integrated into the nuclear.

1) TAT interacts with HIV LTR promoter to produce RNAPII (regulatory protein)

2) REV controls late-gene expression (structural) by binding to cis sequence in RNA and controlling RNA splicing (un-spliced and singly-spliced)

3) Assembly and egress occur in cytoplasm or at cell surface.
Term
Distinguish between Antigenic Drift and Antigenic Shift.
Definition
Drift= subtle changes from point mutations

Shift= Dramatic changes from reassortment b/w segmented RNA genomes (influenza)

** remember, reassortment involves exchange of any number of the 8 viral proteins in influenza A with those in influenza B particle)
Term
Which virus is most commonly associated with syncitia formation?
Definition
Multi-nucleated giant cells in HSV
Term
What is the sole reservoir for Polio virus?
Definition
Humans
Term
How are the gp120 (SU) and gp41 (TM) glycoproteins produced during HIV replication?
Definition
Protease cleaves itself and other products from GAG-POL (Pr160)

1) Protease cleaves Pr55 into MA, CA and NC, producing a nucleocapsid core.

2) Protease cleaves ENV precursor protein into SU and TM
Term
What are the 3 primary mechanisms of viral adaptation?
Definition
1) Point Mutations

2) Recombination between related viral strains (pass on mutations)

3) Reassortment of viral genes (segmented RNA genomes)
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