A 371-nucleotide region between the herpes simplex virus type 1 (HSV-1) LAT promoter and the 2-kilobase LAT is not essential for efficient spontaneous reactivation of latent HSV-1

Guey Chuen Perng, Susan M. Slanina, Homayon Ghiasi, Anthony B. Nesburn, Steven L. Wechsler

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Abstract

The herpes simplex virus type 1 (HSV-1) latency-associated transcript (LAT) gene is essential for efficient spontaneous reactivation of HSV-1 from latency. However, neither the mechanism by which LAT carries out this function nor the region of LAT responsible for this function is known. LAT is transcribed as an unstable 8.3-kb RNA that gives rise to a very stable 2-kb LAT RNA that is readily detected in latently infected sensory neurons. We show here that 371 of the 662 nucleotides located between the start of LAT transcription and the 5' end of the 2-kb LAT RNA do not appear to be essential for wild-type levels of spontaneous reactivation in the rabbit ocular model of HSV-1 latency. We deleted LAT nucleotides 76 to 447 from both copies of the LAT gene (one in each viral long repeat) to produce the mutant dLAT371. Rabbits were ocularly infected with dLAT371, and spontaneous reactivation was measured in comparison with the marker-rescued virus dLAT371R. Both dLAT371 and dLAT371R had spontaneous reactivation rates of approximately 13 to 14%. This was consistent with the parental McKrae wild- type virus (11.7%; P = 0.49) and significantly higher than the tAT transcription-negative mutant dLAT2903 (2.4%; P < 0.0001). Southern analysis confirmed that the spontaneously reactivated dLAT371 virus retained the deletion in both copies of LAT. Therefore, it appeared that the function of EAT involved in efficient spontaneous reactivation mapped outside the 371- nucleotide region deleted from the LAT gene of dLAT371.

Original languageEnglish
Pages (from-to)2014-2018
Number of pages5
JournalJournal of Virology
Volume70
Issue number3
DOIs
Publication statusPublished - 1996

All Science Journal Classification (ASJC) codes

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

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