02/27e DNA Viruses II Flashcards
How do cells detect virus infection?
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
What two pathways are activated when the host innate immune system detects a viral infection?
Production of interferon
NF-kappa-B mediated responses
What genes are stimulated by interferon? What is the result of this stimulation?
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
What genes are regulated by NF-kappa-B?
Lots of cytokines
Cell adhesion molecules
Acute phase response proteins
How do poxviruses respond to cytokine release? Name three ways
Inhibit cytokine synthesis
Modify normal cytokine-receptor interactions
Interfere with signaling pathways
What is a major way in which some viruses modify cytokine-receptor interactions?
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
What signaling pathways do viruses often interfere with in order to avoid an immune response? Name four
PAMP receptor pathways
Caspase signaling pathways that cause apoptosis
Interferon pathways
Pathways that lead to NF-kappa-B activation
How do natural killer cells recognize non-self?
Recognize aberrant or absent MHC Class I expression
What is the typical way in which DNA viruses evade the adaptive immune system?
Establishment of a latent infection
What class of DNA viruses does NOT establish latent infections?
Poxviruses
What are the four phases of latency HSV-1 infection?
1) Establishment
2) Maintenance
3) Reactivation
4) Lytic replication
What is involved in the establishment phase of a latent infection of HSV-1?
Primary infection - virus replicates in epithelial cells
Virus enters the nerves of infected tissues
Viral DNA circularizes in the nucleus (in the trigeminal ganglion)
What are the major characteristics of the maintenance phase of a latent infection?
The lytic pattern of viral gene expression is NOT active
Infectious virus is NOT detectable
What can stimulate the reactivation of a latent virus?
Local trauma (such as surgery) Systemic stimuli such as stress, UV radiation, immunosuppression, or menstruation
What is involved in reactivation of a latent virus?
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
How do reactivated latent viruses evade the immune system?
Interfere with antigen presentation by MHC Class I molecules
Interfere with NK lysis of aberrant cells
Why might large DNA viruses like herpesvirus and poxvirus be easier to target with antiviral drugs than other smaller DNA viruses?
They have more virus-specific proteins and are less dependent on host mechanisms for replication
How does acyclovir work?
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
What are two problems with acyclovir treatment?
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
What rather unusual characteristics of the smallpox virus contributed to the eradication of the virus? Name five
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
What type of vaccine is the HPV vaccine?
Virus-like particle vaccine
Is the HPV vaccine helpful for people who are already infected with one of the targeted virus strains?
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
