Pellett: Virology - Pathogenesis Flashcards
Viruses
Result of infection:
Relationship between viruses and disease
3 other principles of viral infections
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
- Local vs. systemic infections
- Seasonality
- Various incubation periods: time to disease
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
Routes of Person-to-person transmission (7):
Person-to-person transmission: some paths more likely if illness present; others if relatively healthy Fecal-oral Respiratory Animal bite Arthropods Sexual Bloodborne Vertically (transplacental, genetic)
Incubation periods of:
Influenza Common cold Herpes Rabies AIDS
Influenza: 1-2 days Common cold: 1-3 days Herpes: 5-8 days Rabies: 30- 100 days AIDS: 1-10 years
Latent State:
Cellular:
Organismal:
Cellular: no infectious particles produced; can be reactivated to lytic state
Organismal: period between infection and disease
Persistent Infection:
Cellular:
Organismal:
Cellular: lytic state, equilibrium between cell death and production (but still making virus paticles)
Organismal: continuous inhabitation of the host
Abortive Infection:
Abortive Infection: non-productive, not reactivation
Patterns of Viral Infection:
o Acute:
o Latent:
o Progressive:
o Chronic or Persistent:
o Acute: GI viruses
o Latent: HSV (reactivations occur)
o Progressive: HIV or hep C
o Chronic or Persistent: HIV or hep C
Patterns of Viral Infection:
o Failure to clear all evidence of infection:
o Subclinical/asymptomatic:
o Slow:
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)
Genes groups based on contribution to virulence:
Basic Replication Functions:
Immunevasion:
Cell and tissue tropism:
Toxic products:
Genes groups based on contribution to virulence:
Basic Replication Functions: viral RNA polymerase
Immunevasion: proteins that downregulate Ag presentation
Cell and tissue tropism: HIV uses CD4 as cellular receptor
Toxic products: rotavirus NSP4 induces diarrhea
Disease in immunocompromised infections (2):
Opportunistic infections (OI)
De novo vs. prior infection
Why does viral load matter?
The larger the load, the higher the probability of disease
Viruses and Cancer: generally unintended by-products of niche-management by the virus
HPV:
HTLV-1:
HHV-8:
EBV:
Hep B/Hep C:
Viruses and Cancer: generally unintended by-products of niche-management by the virus
HPV and cervical cancer
HTLV-1 and T cell leukemia
HHV-8 and Kaposi’s sarcoma
EBV and Burkitt’s Lymphoma and nasopharyngeal carcinoma
Hep B/Hep C and liver cancer
Innate immunity (3):
Physical barriers: skin, mucosa, respiratory filters
Intracellular defenses: IFN (and other cytokines), PKR, RNase, stress responses, cell-death (apoptosis, necrosis, autophagy)
NK cells, macrophages and neutrophils
Acquired immunity (2):
Effect of abs against virions:
Effect of abs against viral proteins on cell surfaces:
Antibodies and complement
- Abs against virions: neutralization
- 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
T cells
Viral immune escape
ESSENTIALLY EVERY DEFENSE CAN BE BLOCKED OR CIRCUMVENTED BY A VIRUS
Manipulation of the immune system:
What type of virus?
Large DNA viruses:
What are host-derived?
- All viruses do it
- Large DNA viruses dedicate more genes to the task
- Many viral immunomodulatory genes are host-derived
Targets for immune evasion:
Innate vs. Adaptive Responses
Innate Defenses:
- Apoptosis
- IFN responses
- PKR pathway (proten kinase RNA-activated pathway)
Adaptive Responses:
- Ag prensetation
What is the PKR pathway?
Activated by:
Net result:
What can the virus do?
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)
Diagnostic tests that detect the agent (5):
o Cytology o Electron microscopy o Direct fluorescent Ab (DFA) o Cell culture o Nucleic Acids (PCR)
Diagnostic tests that Detect Response to the Agent:
Serotology (look for Abs against the agent)
What must antivirals do?
Must selectively inhibit viral functions without damaging the host
Targets of antivirals (5):
Targets: every step in replication cycle is potential target
Attachment and entry (fusion inhibitors)
Uncoating (ion channel blockers)
Genome replication (polymerase inhibitors)
Protein synthesis/assembly and maturation (protease inhibitors)
Egress and release (neuraminidase inhibitors)
Examples:
Fusion inhibitors:
Ion channel blockers:
Polymerase inhibitors:
Protease inhibitors:
Neuraminidase inhibitors:
Fusion inhibitors: Enfuvirtide (T-20)
Ion channel blockers: Amantadine, Rimantadine
Polymerase inhibitors: Acyclovir, Zidovudine, Efavirenz
Protease inhibitors: Saquinavir, Ritonavir
Neuraminidase inhibitors: Zanamivir
