An HSV LAT Null Mutant Reactivates Slowly from Latent Infection and Makes Small Plaques on CV-1 Monolayers

Block, Timothy M.; Deshmane, Satish L.; Masonis, John L.; Maggioncalda, John; Valyi-Nagi, Tiber; Fraser, Nigel W.

doi:10.1006/viro.1993.1078

Cited by 92 publications

(95 citation statements)

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“…Human neuroblastoma SY5Y cells were grown in RPMI medium with 7% calf serum. HSV-1 strain 17 and the LAT deletion viruses 17N/H and ⌬Sty (6,30) were used in the experiments.…”

Section: Cells and Virusesmentioning

confidence: 99%

“…Early studies hypothesized that the 2.0-kb LAT intron was involved in an antisense suppression mechanism because it overlaps the 3Ј end of ICP0 mRNA (50). Other groups have shown that several LAT region deletion viruses exhibit a delayed reactivation phenotype in various animal models (6,18,25,48,52). Furthermore, studies have suggested that LATs play a role in promoting efficient establishment of latency in trigeminal ganglia of both mice (44) and rabbits (37).…”

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confidence: 99%

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Regions of the Herpes Simplex Virus Type 1 Latency-Associated Transcript That Protect Cells from Apoptosis In Vitro and Protect Neuronal Cells In Vivo

Ahmed

Lock

Miller

et al. 2002

J Virol

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154

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“…Human neuroblastoma SY5Y cells were grown in RPMI medium with 7% calf serum. HSV-1 strain 17 and the LAT deletion viruses 17N/H and ⌬Sty (6,30) were used in the experiments.…”

Section: Cells and Virusesmentioning

confidence: 99%

mentioning

confidence: 99%

Regions of the Herpes Simplex Virus Type 1 Latency-Associated Transcript That Protect Cells from Apoptosis In Vitro and Protect Neuronal Cells In Vivo

Ahmed

Lock

Miller

et al. 2002

J Virol

Self Cite

154

134

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“…A stable 2 kb LAT intron is spliced from the primary transcript (Farrell et al, 1991) and is the major LAT expressed during neuronal latency (Dobson et al, 1989;Spivack & Fraser, 1988;Stevens, 1990;Wechsler et al, 1988Wechsler et al, , 1989Zwaagstra et al, 1989). in mice (Block et al, 1993;Devi-Rao et al, 1994;Leib et al, 1989;Perng et al, 2001b;Sawtell & Thompson, 1992;Steiner et al, 1989). The large 8?3 kb LAT overlaps and is antisense to ICP0, ICP34.5 and part of ICP4 (Rock et al, 1987b;Stevens et al, 1987).…”

Section: Introductionmentioning

confidence: 99%

The bovine herpesvirus-1 LR ORF2 is critical for this gene's ability to restore the high wild-type reactivation phenotype to a herpes simplex virus-1 LAT null mutant

Mott

Osório

Jin

et al. 2003

Journal of General Virology

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The bovine herpesvirus-1 LR ORF2 is critical for this gene's ability to restore the high wild-type reactivation phenotype to a herpes simplex virus-1 LAT null mutant During neuronal latency of herpes simplex virus (HSV)-1, the latency-associated transcript (LAT) is the only viral gene readily detectable. LAT is required for the high-level reactivation phenotype in animal models. LAT's anti-apoptotic activity was recently demonstrated by our group and it was proposed that LAT's anti-apoptotic function is involved in enhancing the reactivation phenotype. Recently, using chimeric virus CJLAT, it was shown that the reactivation phenotype of LAT " mutant dLAT2903 can be restored to wild-type levels by inserting the bovine herpes virus (BHV)-1 latency-related (LR) gene into the LAT locus of this HSV-1 LAT deletion mutant. Although transcription of the LR gene, like LAT, inhibits apoptosis, LR appears to be multifunctional. To investigate whether the LR gene's anti-apoptotic function was responsible for restoring the high-reactivation phenotype, a mutated BHV-1 LR gene was inserted into the LAT locus of HSV-1 generating the chimeric virus CJLATmut. This mutation consists of three stop codons inserted just after the ATG of the first LR open reading frame (ORF2). In plasmids and in a BHV-1 mutant, this mutation eliminated the LR gene's anti-apoptotic activity, strongly suggesting that ORF2 encodes a protein responsible for LR's anti-apoptotic activity. Reactivation of the CJLATmut virus, in both rabbits and mice, was significantly lower than in wild-type McKrae virus (P=0?0001 and P=0?0003, respectively) and CJLAT virus, containing wild-type LR in place of LAT (P<0?0001) and was similar to LAT " dLAT2903 (P=0?8 and P=0?7, respectively). Thus, disruption of BHV-1 LR ORF2 eliminated the high-reactivation phenotype. INTRODUCTIONOver 80 % of adults in the United States harbour latent herpes simplex virus type 1 (HSV-1). Following primary peripheral infection of the eye, HSV-1 travels along axons via antegrade transport to sensory neurons of the trigeminal ganglia (TG) where latency is established. The latent virus reactivates sporadically as a result of stress, UV exposure and other unknown stimuli. Reactivations can also occur in the absence of known stimuli, which we have operationally defined as spontaneous reactivation. Following reactivation, HSV-1 travels along axons in a retrograde direction to the initial infection site, where it can replicate and cause recurrent disease (Andreansky et al., 1998;Roizman & Whitley, 2001). Recurrent HSV-1 infection in the eye can cause corneal scarring leading to the loss of vision. As a result, HSV-1 is one of the leading infectious causes of corneal blindness in the developed world (Liesegang et al., 1989). The mechanism(s) by which the latent virus reactivates and causes disease are currently not completely understood.The only gene that is actively transcribed during HSV-1 neuronal latency is the latency-associated transcript (LAT) (Rock et al., 1987b; Stevens et al., 1987). A stab...

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“…LAT plays an important role in the HSV latency-reactivation cycle since LAT null mutants have significantly reduced reactivation phenotypes in mice and rabbits while otherwise having wild-type like replication [5][6][7][8][9][10][11]. LAT has anti-apoptosis activity [12][13][14][15][16][17][18][19].…”

mentioning

confidence: 99%

Introducing point mutations into the ATGs of the putative open reading frames of the HSV-1 gene encoding the latency associated transcript (LAT) reduces its anti-apoptosis activity

Carpenter

Henderson

Hsiang

et al. 2008

Microbial Pathogenesis

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An HSV LAT Null Mutant Reactivates Slowly from Latent Infection and Makes Small Plaques on CV-1 Monolayers

Cited by 92 publications

References 0 publications

Regions of the Herpes Simplex Virus Type 1 Latency-Associated Transcript That Protect Cells from Apoptosis In Vitro and Protect Neuronal Cells In Vivo

Regions of the Herpes Simplex Virus Type 1 Latency-Associated Transcript That Protect Cells from Apoptosis In Vitro and Protect Neuronal Cells In Vivo

The bovine herpesvirus-1 LR ORF2 is critical for this gene's ability to restore the high wild-type reactivation phenotype to a herpes simplex virus-1 LAT null mutant

Introducing point mutations into the ATGs of the putative open reading frames of the HSV-1 gene encoding the latency associated transcript (LAT) reduces its anti-apoptosis activity

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