A novel herpes simplex virus type 1 transcript (AL-RNA) antisense to the 5′ end of the latency-associated transcript produces a protein in infected rabbits

Guey Chuen Perng, Barak Maguen, Ling Jin, Kevin R. Mott, John Kurylo, Lbachir BenMohamed, Ada Yukht, Nelson Osorio, Anthony B. Nesburn, Gail Henderson, Melissa Inman, Clinton J Jones, Steven L. Wechsler

Research output: Contribution to journalArticle

40 Citations (Scopus)

Abstract

Following primary ocular infection, herpes simplex virus type 1 (HSV-1) establishes a lifelong latent infection in sensory neurons of the trigeminal ganglia. Latency-associated transcript (LAT), the only known viral gene abundantly transcribed during HSV-1 neuronal latency, is required for high levels of reactivation. Recently we showed that three different mutants that do not alter the LAT promoter but contain deletions within the 5′ end of the primary LAT transcript affect viral virulence (G. C. Perng et al., J. Virol. 75:9018-9028, 2001). In contrast, in LAT-null mutants viral virulence appears unaltered (T. M. Block et al., Virology 192:618-630, 1993; D. C. Bloom et al., J: Virol. 68:1283-1292, 1994; J. M. Hill et al., Virology 174:117-125, 1990; G. C. Perng et al., J. Virol. 68:8045-8055, 1994; F. Sedarati, K. M. Izumi, E. K. Wagner, and J. G. Stevens, J. Virol. 63:4455-4458, 1989). We therefore hypothesized that the 5′ end of LAT and/or an as yet unidentified gene that overlaps part of this region is involved in viral virulence. We report here on the discovery and initial characterization of a novel HSV-1 RNA consistent with such a putative gene. The novel RNA was antisense to the 5′ end of LAT and was designated AL-RNA (anti-LAT sense RNA). The AL-RNA overlapped the core LAT promoter and the first 158 nucleotides of the 5′ end of the primary LAT transcript. AL-RNA was detected in extracts from neuron-like cells (PC-12) infected with wild-type HSV-1 but not in cells infected with a mutant with the AL region deleted. The deletions in each of the above three mutants with altered virulence encompass the 5′ end of the AL-RNA, and these mutants cannot transcribe AL. This supports the hypothesis that the AL gene may play a role in viral virulence. Based on comparison to the corresponding genomic sequence, the AL-RNA did not appear to be spliced. The AL-RNA was polyadenylated and contained an open reading frame capable of encoding a protein 56 amino acids in length with a predicted molecular mass of 6.8 kDa. Sera from three of three rabbits infected with wild-type HSV-1 but not sera from any of three rabbits infected with a mutant with the AL-RNA region deleted recognized the Escherichia coil recombinantly expressed AL open reading frame on Western blots. In addition, four of six rabbits infected with wild-type virus developed enzyme-linked immunosorbent assay titers against one or more AL synthetic peptides. These results suggest that an AL protein is produced in vivo.

Original languageEnglish (US)
Pages (from-to)8003-8010
Number of pages8
JournalJournal of virology
Volume76
Issue number16
DOIs
StatePublished - Aug 5 2002

Fingerprint

antisense RNA
Human herpesvirus 1
Antisense RNA
Human Herpesvirus 1
messenger RNA
rabbits
Rabbits
virulence
Virulence
mutants
virology
Proteins
proteins
RNA
Virology
open reading frames
genes
Open Reading Frames
promoter regions
Escherichia

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

Cite this

A novel herpes simplex virus type 1 transcript (AL-RNA) antisense to the 5′ end of the latency-associated transcript produces a protein in infected rabbits. / Perng, Guey Chuen; Maguen, Barak; Jin, Ling; Mott, Kevin R.; Kurylo, John; BenMohamed, Lbachir; Yukht, Ada; Osorio, Nelson; Nesburn, Anthony B.; Henderson, Gail; Inman, Melissa; Jones, Clinton J; Wechsler, Steven L.

In: Journal of virology, Vol. 76, No. 16, 05.08.2002, p. 8003-8010.

Research output: Contribution to journalArticle

Perng, GC, Maguen, B, Jin, L, Mott, KR, Kurylo, J, BenMohamed, L, Yukht, A, Osorio, N, Nesburn, AB, Henderson, G, Inman, M, Jones, CJ & Wechsler, SL 2002, 'A novel herpes simplex virus type 1 transcript (AL-RNA) antisense to the 5′ end of the latency-associated transcript produces a protein in infected rabbits', Journal of virology, vol. 76, no. 16, pp. 8003-8010. https://doi.org/10.1128/JVI.76.16.8003-8010.2002
Perng, Guey Chuen ; Maguen, Barak ; Jin, Ling ; Mott, Kevin R. ; Kurylo, John ; BenMohamed, Lbachir ; Yukht, Ada ; Osorio, Nelson ; Nesburn, Anthony B. ; Henderson, Gail ; Inman, Melissa ; Jones, Clinton J ; Wechsler, Steven L. / A novel herpes simplex virus type 1 transcript (AL-RNA) antisense to the 5′ end of the latency-associated transcript produces a protein in infected rabbits. In: Journal of virology. 2002 ; Vol. 76, No. 16. pp. 8003-8010.
@article{20fc6c8969db497f9285294223cb694b,
title = "A novel herpes simplex virus type 1 transcript (AL-RNA) antisense to the 5′ end of the latency-associated transcript produces a protein in infected rabbits",
abstract = "Following primary ocular infection, herpes simplex virus type 1 (HSV-1) establishes a lifelong latent infection in sensory neurons of the trigeminal ganglia. Latency-associated transcript (LAT), the only known viral gene abundantly transcribed during HSV-1 neuronal latency, is required for high levels of reactivation. Recently we showed that three different mutants that do not alter the LAT promoter but contain deletions within the 5′ end of the primary LAT transcript affect viral virulence (G. C. Perng et al., J. Virol. 75:9018-9028, 2001). In contrast, in LAT-null mutants viral virulence appears unaltered (T. M. Block et al., Virology 192:618-630, 1993; D. C. Bloom et al., J: Virol. 68:1283-1292, 1994; J. M. Hill et al., Virology 174:117-125, 1990; G. C. Perng et al., J. Virol. 68:8045-8055, 1994; F. Sedarati, K. M. Izumi, E. K. Wagner, and J. G. Stevens, J. Virol. 63:4455-4458, 1989). We therefore hypothesized that the 5′ end of LAT and/or an as yet unidentified gene that overlaps part of this region is involved in viral virulence. We report here on the discovery and initial characterization of a novel HSV-1 RNA consistent with such a putative gene. The novel RNA was antisense to the 5′ end of LAT and was designated AL-RNA (anti-LAT sense RNA). The AL-RNA overlapped the core LAT promoter and the first 158 nucleotides of the 5′ end of the primary LAT transcript. AL-RNA was detected in extracts from neuron-like cells (PC-12) infected with wild-type HSV-1 but not in cells infected with a mutant with the AL region deleted. The deletions in each of the above three mutants with altered virulence encompass the 5′ end of the AL-RNA, and these mutants cannot transcribe AL. This supports the hypothesis that the AL gene may play a role in viral virulence. Based on comparison to the corresponding genomic sequence, the AL-RNA did not appear to be spliced. The AL-RNA was polyadenylated and contained an open reading frame capable of encoding a protein 56 amino acids in length with a predicted molecular mass of 6.8 kDa. Sera from three of three rabbits infected with wild-type HSV-1 but not sera from any of three rabbits infected with a mutant with the AL-RNA region deleted recognized the Escherichia coil recombinantly expressed AL open reading frame on Western blots. In addition, four of six rabbits infected with wild-type virus developed enzyme-linked immunosorbent assay titers against one or more AL synthetic peptides. These results suggest that an AL protein is produced in vivo.",
author = "Perng, {Guey Chuen} and Barak Maguen and Ling Jin and Mott, {Kevin R.} and John Kurylo and Lbachir BenMohamed and Ada Yukht and Nelson Osorio and Nesburn, {Anthony B.} and Gail Henderson and Melissa Inman and Jones, {Clinton J} and Wechsler, {Steven L.}",
year = "2002",
month = "8",
day = "5",
doi = "10.1128/JVI.76.16.8003-8010.2002",
language = "English (US)",
volume = "76",
pages = "8003--8010",
journal = "Journal of Virology",
issn = "0022-538X",
publisher = "American Society for Microbiology",
number = "16",

}

TY - JOUR

T1 - A novel herpes simplex virus type 1 transcript (AL-RNA) antisense to the 5′ end of the latency-associated transcript produces a protein in infected rabbits

AU - Perng, Guey Chuen

AU - Maguen, Barak

AU - Jin, Ling

AU - Mott, Kevin R.

AU - Kurylo, John

AU - BenMohamed, Lbachir

AU - Yukht, Ada

AU - Osorio, Nelson

AU - Nesburn, Anthony B.

AU - Henderson, Gail

AU - Inman, Melissa

AU - Jones, Clinton J

AU - Wechsler, Steven L.

PY - 2002/8/5

Y1 - 2002/8/5

N2 - Following primary ocular infection, herpes simplex virus type 1 (HSV-1) establishes a lifelong latent infection in sensory neurons of the trigeminal ganglia. Latency-associated transcript (LAT), the only known viral gene abundantly transcribed during HSV-1 neuronal latency, is required for high levels of reactivation. Recently we showed that three different mutants that do not alter the LAT promoter but contain deletions within the 5′ end of the primary LAT transcript affect viral virulence (G. C. Perng et al., J. Virol. 75:9018-9028, 2001). In contrast, in LAT-null mutants viral virulence appears unaltered (T. M. Block et al., Virology 192:618-630, 1993; D. C. Bloom et al., J: Virol. 68:1283-1292, 1994; J. M. Hill et al., Virology 174:117-125, 1990; G. C. Perng et al., J. Virol. 68:8045-8055, 1994; F. Sedarati, K. M. Izumi, E. K. Wagner, and J. G. Stevens, J. Virol. 63:4455-4458, 1989). We therefore hypothesized that the 5′ end of LAT and/or an as yet unidentified gene that overlaps part of this region is involved in viral virulence. We report here on the discovery and initial characterization of a novel HSV-1 RNA consistent with such a putative gene. The novel RNA was antisense to the 5′ end of LAT and was designated AL-RNA (anti-LAT sense RNA). The AL-RNA overlapped the core LAT promoter and the first 158 nucleotides of the 5′ end of the primary LAT transcript. AL-RNA was detected in extracts from neuron-like cells (PC-12) infected with wild-type HSV-1 but not in cells infected with a mutant with the AL region deleted. The deletions in each of the above three mutants with altered virulence encompass the 5′ end of the AL-RNA, and these mutants cannot transcribe AL. This supports the hypothesis that the AL gene may play a role in viral virulence. Based on comparison to the corresponding genomic sequence, the AL-RNA did not appear to be spliced. The AL-RNA was polyadenylated and contained an open reading frame capable of encoding a protein 56 amino acids in length with a predicted molecular mass of 6.8 kDa. Sera from three of three rabbits infected with wild-type HSV-1 but not sera from any of three rabbits infected with a mutant with the AL-RNA region deleted recognized the Escherichia coil recombinantly expressed AL open reading frame on Western blots. In addition, four of six rabbits infected with wild-type virus developed enzyme-linked immunosorbent assay titers against one or more AL synthetic peptides. These results suggest that an AL protein is produced in vivo.

AB - Following primary ocular infection, herpes simplex virus type 1 (HSV-1) establishes a lifelong latent infection in sensory neurons of the trigeminal ganglia. Latency-associated transcript (LAT), the only known viral gene abundantly transcribed during HSV-1 neuronal latency, is required for high levels of reactivation. Recently we showed that three different mutants that do not alter the LAT promoter but contain deletions within the 5′ end of the primary LAT transcript affect viral virulence (G. C. Perng et al., J. Virol. 75:9018-9028, 2001). In contrast, in LAT-null mutants viral virulence appears unaltered (T. M. Block et al., Virology 192:618-630, 1993; D. C. Bloom et al., J: Virol. 68:1283-1292, 1994; J. M. Hill et al., Virology 174:117-125, 1990; G. C. Perng et al., J. Virol. 68:8045-8055, 1994; F. Sedarati, K. M. Izumi, E. K. Wagner, and J. G. Stevens, J. Virol. 63:4455-4458, 1989). We therefore hypothesized that the 5′ end of LAT and/or an as yet unidentified gene that overlaps part of this region is involved in viral virulence. We report here on the discovery and initial characterization of a novel HSV-1 RNA consistent with such a putative gene. The novel RNA was antisense to the 5′ end of LAT and was designated AL-RNA (anti-LAT sense RNA). The AL-RNA overlapped the core LAT promoter and the first 158 nucleotides of the 5′ end of the primary LAT transcript. AL-RNA was detected in extracts from neuron-like cells (PC-12) infected with wild-type HSV-1 but not in cells infected with a mutant with the AL region deleted. The deletions in each of the above three mutants with altered virulence encompass the 5′ end of the AL-RNA, and these mutants cannot transcribe AL. This supports the hypothesis that the AL gene may play a role in viral virulence. Based on comparison to the corresponding genomic sequence, the AL-RNA did not appear to be spliced. The AL-RNA was polyadenylated and contained an open reading frame capable of encoding a protein 56 amino acids in length with a predicted molecular mass of 6.8 kDa. Sera from three of three rabbits infected with wild-type HSV-1 but not sera from any of three rabbits infected with a mutant with the AL-RNA region deleted recognized the Escherichia coil recombinantly expressed AL open reading frame on Western blots. In addition, four of six rabbits infected with wild-type virus developed enzyme-linked immunosorbent assay titers against one or more AL synthetic peptides. These results suggest that an AL protein is produced in vivo.

UR - http://www.scopus.com/inward/record.url?scp=0036312046&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0036312046&partnerID=8YFLogxK

U2 - 10.1128/JVI.76.16.8003-8010.2002

DO - 10.1128/JVI.76.16.8003-8010.2002

M3 - Article

VL - 76

SP - 8003

EP - 8010

JO - Journal of Virology

JF - Journal of Virology

SN - 0022-538X

IS - 16

ER -