An acutely and latently expressed herpes simplex virus 2 viral microRNA inhibits expression of ICP34.5, a viral neurovirulence factor.
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.
Tang
Shuang
S
Division of Viral Products, Office of Vaccines Research and Review, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, MD 20892, USA.
Bertke
Andrea S
AS
Patel
Amita
A
Wang
Kening
K
Cohen
Jeffrey I
JI
Krause
Philip R
PR
D000328:Adult; D000818:Animals; D001483:Base Sequence; D015152:Blotting, Northern; D002460:Cell Line; D017931:DNA Primers / Q000235:genetics; D005727:Ganglia, Spinal / Q000378:metabolism / Q000821:virology; D040461:Gene Components; D015967:Gene Expression Regulation, Viral / Q000235:genetics*; D006168:Guinea Pigs; D018258:Herpesvirus 2, Human / Q000235:genetics*; D006801:Humans; D008156:Luciferases; D008297:Male; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D008856:Microscopy, Fluorescence; D008875:Middle Aged; D008969:Molecular Sequence Data; D009475:Neurons, Afferent / Q000821:virology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014764:Viral Proteins / Q000378:metabolism*; D017735:Virus Latency / Q000235:genetics*
D017931:DNA Primers; D035683:MicroRNAs; D014764:Viral Proteins; C066469:gamma 34.5 protein, Human herpesvirus 1; D008156:Luciferases