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Herpes Simplex Virus 1

HSV-1 naturally infects the trigeminal ganglia of humans. A branch goes to the eyes, one to the nose, and one to the mouth. The virus can also go latent in the TG, and from there can reactivate from the latent state to cause a recurrent infection. IB4 neurons harbor virus that produce a lytic infection with full viral replication. A5 neurons tend to harbor virus that has gone into latency. In the latent state to lytic cycle genes are expressed.

HSV-1 can infect mouse feet, leading to an infection of the dorsal root ganglia. During latency, the only viral RNA expressed is called the latency-associated transcript, aka LAT. Stresses to the nervous system can cause the virus to reactivate from the latent state, leading to viral replication and transport of the newly made viruses back down the axon and out to the surface.

Immediate-Early GenesThere are 5 of these. Of these, ICP0 and ICP4 activate transcription of the early and late viral genes.
Early GenesThese proteins help make the cell get ready to replicate the viral DNA. There are many of these, but 2 important ones are the viral thymidine kinase and the viral DNA polymerase. Synthesis of these is strongly actiated by an Oct1-VP16 complex. This complex binds the TAATGARAT motif. Oct1 is a cellular transcription factor. VP16 is a viral protein packaged in the virion. VP16 contains an acid-blob motif to help recruit transcription factor to the 5 IE promoters.
Late GenesThese encode the capsid and various glycoproteins for attachment and penetration into the next cell. These form empty capsids, which are filled with viral DNA.

LAT RNA is anti-sense to part of the third exon of the ICP0 mRNA. At first investigators thought that LAT might be an mRNA encoding a reactivation protein, but LAT is actually a stable intron.

Inhibition of viral growth: action of the viral thymdine kinase protein. Thymidine kinase blocks Viral DNAP.

Summary of HSV latency: 1) viral DNA is an episome. 2) IE, early and alte genes shut off. 3) LAT is the only viral RNA 4) LAT is antisense to ICP0 mRNA. 5) Reactivations vary in the amount of virus released and the presence or absence of clinical symptoms.

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