12 - Persistent Viral Infections Flashcards
1
Q
Persistent infections
A
Those in which the virus, its genome, or parts of its genome persists in its host for the long term (months, years, or lifetime)
2
Q
Two main types of persistent infection
A
Chronic and latent
3
Q
Chronic infections
A
- Lytic replication in a multicellular organism occuring at low levels and ongoing for longer than
the duration of the cell division cycle of most host cells - Immune system takes long time to eliminate
4
Q
Latent infections
A
- Virus exits the lytic cycle and persists in host cells, (in form of a few nucleic acids and
proteins), without causing production of new virions. - Viral genomes persist even when viral proteins are not detectable.
- Exit from latency and entry back into the lytic cycle typically occurs when the host cell encounters environmental stress.
5
Q
Alpha herpesvirinae
A
- HSV1
- HSV2
- Varicella zoster virus
6
Q
Beta herpesvirinae
A
- HCMV
- HSV6
- HHV7
7
Q
Gamma herpesvirinae
A
- EBV
- Kaposi’s sarcoma associated herpesvirus
8
Q
Where does human herpesvirus establish latent infection
A
Trigeminal ganglia
9
Q
Latent herpesvirus infections
A
- HSV-1 and HSV-2
- Begin with lytic infection of an epithelium
- Virus replicates in the epithelium and latency is initiated when some of the offspring virions infect the
sensory neurons that innervate the epithelium - Virions that enter the terminally differentiated neurons traffic along the cytoskeleton to the cell nucleus, in the spinal column
- Herpesvirus genome circularizes and persists as an episome in the nuclei of latently infected cells
-Multiple copies of episomal viral DNA remain in nucleus
10
Q
What is needed to maintain latency in HSV
A
- Lytic gene expression must be blocked
- Apoptosis and innate immunity must be blocked
11
Q
How is latency maintain in HSV
A
- HSV encodes miRNAs that inhibit viral proteins that control transcription and replication
- HSV Encodes two LATs that inhibit apoptosis in neurons
12
Q
LATs
A
Latency associated transcripts
13
Q
What is Herpesvirus latency is influenced by
A
adaptive immune responses
14
Q
HSV-1-infected neurons surrounded by T cells in the TG
A
- Limits viral reactivation which would otherwise lead to lytic replication of the virus, thus hampering the generation of infectious virions from these cells
- HSV1 specific CD8 in contact with TG neurons were shown to block viral reactivation through the release of granzymes that degrade viral proteins
15
Q
Viral persistence in the ependymal zone of the brain
A
- Related to T cells expressing exhaustion markers (e.g. programmed death 1 - PD-1)
- Isolated T cells were unable to control HSV-1 infection ex vivo and secreted less interferon (IFN)-γ in
comparison to T cells isolated from TG - Reactivation is also triggered by weakening of immunity brought about by aging or by infections such as HIV
