Pellett: Virology - Pathogenesis

Question 1

Viruses

Result of infection:

Relationship between viruses and disease

3 other principles of viral infections

Answer 1

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

Question 2

Outcome of infection determined by the interaction of the virus and the host

Answer 2

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

Question 3

Routes of Person-to-person transmission (7):

Answer 3

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)

Question 4

Incubation periods of:

Influenza
Common cold
Herpes
Rabies
AIDS

Answer 4

Influenza: 1-2 days
Common cold: 1-3 days
Herpes: 5-8 days
Rabies: 30- 100 days
AIDS: 1-10 years

Question 5

Latent State:

Cellular:
Organismal:

Answer 5

Cellular: no infectious particles produced; can be reactivated to lytic state

Organismal: period between infection and disease

Question 6

Persistent Infection:

Cellular:
Organismal:

Answer 6

Cellular: lytic state, equilibrium between cell death and production (but still making virus paticles)

Organismal: continuous inhabitation of the host

Question 7

Abortive Infection:

Answer 7

Abortive Infection: non-productive, not reactivation

Question 8

Patterns of Viral Infection:

o Acute:
o Latent:
o Progressive:
o Chronic or Persistent:

Answer 8

o Acute: GI viruses
o Latent: HSV (reactivations occur)
o Progressive: HIV or hep C
o Chronic or Persistent: HIV or hep C

Question 9

Patterns of Viral Infection:

o Failure to clear all evidence of infection:
o Subclinical/asymptomatic:
o Slow:

Answer 9

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)

Question 10

Genes groups based on contribution to virulence:

Basic Replication Functions:

Immunevasion:

Cell and tissue tropism:

Toxic products:

Answer 10

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

Question 11

Disease in immunocompromised infections (2):

Answer 11

Opportunistic infections (OI)

De novo vs. prior infection

Question 12

Why does viral load matter?

Answer 12

The larger the load, the higher the probability of disease

Question 13

Viruses and Cancer: generally unintended by-products of niche-management by the virus

HPV:

HTLV-1:

HHV-8:

EBV:

Hep B/Hep C:

Answer 13

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

Question 14

Innate immunity (3):

Answer 14

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

Question 15

Acquired immunity (2):

Effect of abs against virions:
Effect of abs against viral proteins on cell surfaces:

Answer 15

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

Question 16

Viral immune escape

Answer 16

ESSENTIALLY EVERY DEFENSE CAN BE BLOCKED OR CIRCUMVENTED BY A VIRUS

Question 17

Manipulation of the immune system:

What type of virus?
Large DNA viruses:
What are host-derived?

Answer 17

• All viruses do it
• Large DNA viruses dedicate more genes to the task
• Many viral immunomodulatory genes are host-derived

Question 18

Targets for immune evasion:

Innate vs. Adaptive Responses

Answer 18

Innate Defenses:

• Apoptosis
• IFN responses
• PKR pathway (proten kinase RNA-activated pathway)

Adaptive Responses:
- Ag prensetation

Question 19

What is the PKR pathway?
Activated by:
Net result:
What can the virus do?

Answer 19

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)

Question 20

Diagnostic tests that detect the agent (5):

Answer 20

o	Cytology
o	Electron microscopy
o	Direct fluorescent Ab (DFA)
o	Cell culture
o	Nucleic Acids (PCR)

Question 21

Diagnostic tests that Detect Response to the Agent:

Answer 21

Serotology (look for Abs against the agent)

Question 22

What must antivirals do?

Answer 22

Must selectively inhibit viral functions without damaging the host

Question 23

Targets of antivirals (5):

Answer 23

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)

Question 24

Examples:

Fusion inhibitors:

Ion channel blockers:

Polymerase inhibitors:

Protease inhibitors:

Neuraminidase inhibitors:

Answer 24

Fusion inhibitors: Enfuvirtide (T-20)

Ion channel blockers: Amantadine, Rimantadine

Polymerase inhibitors: Acyclovir, Zidovudine, Efavirenz

Protease inhibitors: Saquinavir, Ritonavir

Neuraminidase inhibitors: Zanamivir

Question 25

Why are antivirals relatively ineffective clinically as compared to bacterial agents?

Answer 25

Many rounds of viral replication has occurred during the incubation period before symptoms develop

Question 26

What is most important to prevent infection

Answer 26

vaccination

Question 27

How is acyclovir activated?

Answer 27

Acyclovir must be phosphorylated by viral thymidine kinase

Question 28

Key Issues (5):

Answer 28

o	Specificity
o	Toxicity
o	Rapid diagnosis
o	Therapeutic threshold
o	Resistance