Chronic Viral Lifestyles Flashcards
What is the end-outcome of an untreated acute infection?
What is the end-outcome of an untreated chronic infection?
Acute adaptive response to the virus–complete clearance or host death.
Incomplete clearance of the virus, but heightened immune state.
Distinguish between a latent and persistent viral infection.
A latent infection involves minimal viral protein expression and/or lysis. It is largely quiescent.
A persistent infection continues replication in the face of an immune response.
As a DNA virus, herpes must locate to the ____ for replication. Describe the sequence of gene transcription there.
Herpesvirus locates to the nucleus, where it sequentially transcribes alpha, beta, and gamma genes. Each transcription occurs at a different sequential point in the infection–for example, gamma genes encode capsid proteins for assembly, and wouldn’t be active in a latent infection).
What advantages are conferred by latent infection?
Without lysis and replication, the immune response will be less able to detect the infection. By integrating into the host genome, the viral genome will be maintained in the long-term.
What disadvantages are conferred by latent infection?
Spread and replication are slow. Incidental death of the host cell will also take out the infecting virus–this method is more successful when infecting long-lived cells.
What is viral reactivation?
How do viruses achieve this despite heightened immunity?
A switch from latent infection to active (lytic) replication.
If latency is established in long-lived cells, the switch will better resist the immune response. For example, HIV latently infects helper T-cells. Immune response and drugs can only target the lytic cycle, and so infection continues with their cessation.
How do chronic infections overpower the acute adaptive immune response?
Flooding with high levels of antigen impedes formation of immune memory (remember, moderate levels of Ag best facilitate this).
T-cell exhaustion occurs as the overstimuated T-cells upregulate inhibitory receptors. This leads them to quiescence and eventually death.
Why would HIV reduce viral replication when infecting a memory T-cell (as opposed to an activated helper cell)?
By latently infecting the memory cell, the virus stays present despite HAART depleting the lytic load of virus. When treatment stops, enough virus persists to continue infection.
What are some consequences of heightened immunity in latent infection?
What is the source of pathology in latent infection?
The immune response will affect susceptibility to other infections, and may provoke autoimmunity. Presumably, this response can be studied to formulate vaccines.
Usually, pathology either occurs due to immune response or viral reactivation. However, some latent infections can activate oncogenes, causing carcinogenesis without replication (eg EPV).
How are latent infections treated?
Because latent infections hide from the natural immunity (low load), vaccines are less viable.
The lytic cycle is targeted prophylactically or for life-long treatment. Induction of reactivation should help clear the virus in conjunction with these treatments.
How does pathology occur in persistent infections?
Nothing special: Tissue damage due to replication (eg CD4 cell depletion or hepatocyte death), inflammatory response (eg cirrhosis), and occasionally oncogene activation (carcinogenesis!)
How are persistent infections treated?
Long term treatment for the lytic cycle to minimize injury due to replication.
Immunosuppression to minimize injury due to immune response.
