Scientific Publications by FDA Staff

Proc Natl Acad Sci U S A 2008 Aug 5;105(31):10931-6

An acutely and latently expressed herpes simplex virus 2 viral microRNA inhibits expression of ICP34.5, a viral neurovirulence factor.

Tang S, Bertke AS, Patel A, Wang K, Cohen JI, Krause PR

Krause, PR, US FDA, Ctr Biol Evaluat & Res, Off Vaccines Res & Review, Div Viral Prod, HFM-457,29 Lincoln Dr, Bethesda, MD 20892 USA US FDA, Ctr Biol Evaluat & Res, Off Vaccines Res & Review, Div Viral Prod, Bethesda, MD 20892 USA NIAID, Lab Clin Infect Dis, Med Virol Sect, Bethesda, MD 20892 USA

Latency-associated transcript (LAT) sequences regulate herpes simplex virus (HSV) latency and reactivation from sensory neurons. We found a HSV-2 LAT-related microRNA (miRNA) designated miR-I in transfected and infected cells in vitro and in acutely and latently infected ganglia of guinea pigs in vivo. miR-I is also expressed in human sacral dorsal root ganglia latently infected with HSV-2. miR-I is expressed under the LAT promoter in vivo in infected sensory ganglia. We also predicted and identified a HSV-1 LAT exon-2 viral miRNA in a location similar to miR-I, implying a conserved mechanism in these closely related viruses. In transfected and infected cells, miR-I reduces expression of ICP34.5, a key viral neurovirulence factor. We hypothesize that miR-I may modulate the outcome of viral infection in the peripheral nervous system by functioning as a molecular switch for ICP34.5 expression.