Termination of Transcription of LAT Increases the Amounts of ICP0 mRNA but Does Not Alter the Course of HSV-1 Infection in Latently Infected Murine Ganglia.
On entering sensory ganglia, herpes simplex viruses 1 (HSV-1) establishes a latent infection with the synthesis of a latency associated transcript (LAT) or initiates productive infection with expression of a set of immediate early viral proteins. The precise mechanisms how expression of α genes is suppressed during the latency are unknown. One mechanism that has been proposed is illustrated in the case of ICP0, a key immediate early viral regulatory protein. Specifically, the 2 kb LAT intron is complementary to the 3' terminal portion of ICP0 mRNA. To test the hypothesis that accumulation of LAT negatively affects the accumulation of ICP0 mRNA, we inserted a DNA fragment encoding two poly(A) sequences into LAT to early terminate LAT transcript without interrupting the complementary sequence of ICP0 transcript (named as SR1603). Comparisons of the parent (SR1601) and mutant (SR1603) HSV-1 viruses showed the following: Neurons harboring latent SR1603 virus accumulated equivalent amounts of viral DNA but higher amounts of ICP0 mRNA and lower amounts of LAT, when compared to neurons harboring the SR1601 virus. One notable difference between the two viruses is that viral RNA accumulation in explanted ganglia harboring SR1603 virus initiated significantly sooner than that in neurons harboring SR1601 virus, suggesting that ICP0 may act as an activator of viral gene expression in permissive cells. Collectively, these data suggest that increased ICP0 mRNA by suppressed LAT did not affect the establishment of latency in latently infected murine ganglia.
['Jiang|Haifang|H|', 'Wu|Jiaming|J|', 'Liu|Xianjie|X|', 'Lu|Ruitao|R|', 'Zhou|Manling|M|', 'Chen|Meiling|M|', 'Liu|Yonghong|Y|', 'Zhou|Grace Guoying|GG|http://orcid.org/0000-0002-4559-8558', 'Fu|Wenmin|W|http://orcid.org/0000-0002-3290-7921']
D000818:Animals D005260:Female D005724:Ganglia D018259:Herpesvirus 1, Human D051379:Mice D008807:Mice, Inbred BALB C D012333:RNA, Messenger D044767:Ubiquitin-Protein Ligases D017735:Virus Latency
ICP0 Herpes simplex viruses 1 (HSV-1) Latency Latency associated transcript (LAT)