02/27e DNA Viruses II

Question 1

How do cells detect virus infection?

Answer 1

Detect alterations in cell metabolism
Recognize viral components (capsid, nucleic acids, double-stranded RNA)
Toll-like receptors detect foreign RNA, and DNA in the cytoplasm
RIG receptors detect non-self cytoplasmic RNAs

Question 2

What two pathways are activated when the host innate immune system detects a viral infection?

Answer 2

Production of interferon

NF-kappa-B mediated responses

Question 3

What genes are stimulated by interferon? What is the result of this stimulation?

Answer 3

PKR - senses dsRNA and alters translation machinery, resulting in the inhibition of protein synthesis
RNase L - degrades host and viral mRNAs
Can result in apoptosis of the host cell

Question 4

What genes are regulated by NF-kappa-B?

Answer 4

Lots of cytokines
Cell adhesion molecules
Acute phase response proteins

Question 5

How do poxviruses respond to cytokine release? Name three ways

Answer 5

Inhibit cytokine synthesis
Modify normal cytokine-receptor interactions
Interfere with signaling pathways

Question 6

What is a major way in which some viruses modify cytokine-receptor interactions?

Answer 6

Virus encodes a soluble version of a cytokine receptor, which binds to the cytokine and blocks it from binding to its actual membrane-bound receptor and initiating a pro-inflammatory cascade

Question 7

What signaling pathways do viruses often interfere with in order to avoid an immune response? Name four

Answer 7

PAMP receptor pathways
Caspase signaling pathways that cause apoptosis
Interferon pathways
Pathways that lead to NF-kappa-B activation

Question 8

How do natural killer cells recognize non-self?

Answer 8

Recognize aberrant or absent MHC Class I expression

Question 9

What is the typical way in which DNA viruses evade the adaptive immune system?

Answer 9

Establishment of a latent infection

Question 10

What class of DNA viruses does NOT establish latent infections?

Answer 10

Poxviruses

Question 11

What are the four phases of latency HSV-1 infection?

Answer 11

1) Establishment
2) Maintenance
3) Reactivation
4) Lytic replication

Question 12

What is involved in the establishment phase of a latent infection of HSV-1?

Answer 12

Primary infection - virus replicates in epithelial cells
Virus enters the nerves of infected tissues
Viral DNA circularizes in the nucleus (in the trigeminal ganglion)

Question 13

What are the major characteristics of the maintenance phase of a latent infection?

Answer 13

The lytic pattern of viral gene expression is NOT active

Infectious virus is NOT detectable

Question 14

What can stimulate the reactivation of a latent virus?

Answer 14

Local trauma (such as surgery)
Systemic stimuli such as stress, UV radiation, immunosuppression, or menstruation

Question 15

What is involved in reactivation of a latent virus?

Answer 15

Virus begins to multiply again
New virus is transported back to the site of the initial infection
Lytic replication occurs in epithelial cells at the original site

Question 16

How do reactivated latent viruses evade the immune system?

Answer 16

Interfere with antigen presentation by MHC Class I molecules

Interfere with NK lysis of aberrant cells

Question 17

Why might large DNA viruses like herpesvirus and poxvirus be easier to target with antiviral drugs than other smaller DNA viruses?

Answer 17

They have more virus-specific proteins and are less dependent on host mechanisms for replication

Question 18

How does acyclovir work?

Answer 18

Targets viral thymidine kinase and DNA polymerase
ACV is phosphorylated by thymidine kinase and incorporated into nascent viral DNA by the viral DNA polymerase
The phosphorylated ACV complex lacks a 3` OH end, and thus forms a dead-end complex that blocks further replication

Question 19

What are two problems with acyclovir treatment?

Answer 19

Will not target a pre-established latent infection because the targeted enzymes are only expressed during the lytic phase
Long-term treatment promotes the development of mutant viruses that are resistant to the drug

Question 20

What rather unusual characteristics of the smallpox virus contributed to the eradication of the virus? Name five

Answer 20

1) Replicates naturally only in humans (no animal reservoirs)
2) Does not establish persistent or latent infections
3) Does not undergo antigenic changes
4) An effective, inexpensive vaccine was available
5) Smallpox produces a severe, scary disease, which helped to motivate global eradication

Question 21

What type of vaccine is the HPV vaccine?

Answer 21

Virus-like particle vaccine

Question 22

Is the HPV vaccine helpful for people who are already infected with one of the targeted virus strains?

Answer 22

No, because the vaccine only targets proteins that are produced in the late gene expression phase
Latently-infected cells (in the early gene expression phase) will not be targeted