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J. Virol., 08 1997, 5885-5893, Vol 71, No. 8
Copyright © 1997, American Society for Microbiology

A LAT-associated function reduces productive-cycle gene expression during acute infection of murine sensory neurons with herpes simplex virus type 1

DA Garber, PA Schaffer and DM Knipe
Department of Microbiology and Molecular Genetics, Harvard Medical School, Boston, Massachusetts 02115, USA.

Herpes simplex virus (HSV) persists in the human population by establishing long-term latent infections followed by periodic reactivation and transmission. Latent infection of sensory neurons is characterized by repression of viral productive-cycle gene expression, with abundant transcription limited to a single locus that encodes the latency-associated transcripts (LATs). We have observed that LAT- deletion mutant viruses express viral productive-cycle genes in greater numbers of murine trigeminal ganglion neurons than LAT+ HSV type 1 at early times during acute infection but show reduced reactivation from latent infection. Thus, a viral function associated with the LAT region exerts an effect at an early stage of neuronal infection to reduce productive-cycle viral gene expression. These results provide the first evidence that the virus plays an active role in down-regulating productive infection during acute infection of sensory neurons. The effect of down-regulation of productive-cycle gene expression during acute infection may contribute to viral evasion from the host immune responses and to reduced cytopathic effects, thereby facilitating neuronal survival and the establishment of latency.

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