Two open reading frames (ORF1 and ORF2) within the 2.0-kilobase latency-associated transcript of herpes simplex virus type 1 are not essential for reactivation from latency

Fareed, Moin U.; Spivack, Jordan G.

doi:10.1128/jvi.68.12.8071-8081.1994

Cited by 30 publications

(13 citation statements)

References 69 publications

(97 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In addition, the poly(A) insertion viruses preclude downstream transcripts from having a role in reactivation. These results also show that measurable levels of expression of transcripts including downstream translational reading frames, including the recently identified ORF-P (15,27,28,39), controlled by other promoters are not involved with reactivation.…”

Section: Discussionsupporting

confidence: 53%

“…Mutants of HSV-1 and -2 with deletions in the LAT promoter do not reactivate efficiently in several in vivo models (4,5,21,24,37,49), yet the biological mechanism for this apparent linkage between LAT expression and efficient reactivation is unknown. Characterization of several precisely defined mutants has eliminated reasonable mechanisms involving any role for the translation of the major translational reading frames contained within the major LAT introns (15,16); however, mechanisms involving the latent-phase expression of other peptides whose coding sequences are contained within the primary LAT transcript remain a possibility. Also formally consistent with available data in rabbits are other mechanisms requiring the presence of high levels of LAT introns and/or the transcription of the region of the HSV-1 genome encompassed by LAT, either to facilitate the expression of another transcript or to maintain a transcriptionally active viral template.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

A 348-base-pair region in the latency-associated transcript facilitates herpes simplex virus type 1 reactivation

Bloom

Hill

Devi-Rao

et al. 1996

J Virol

102

View full text Add to dashboard Cite

Latency-associated transcript (LAT) promoter deletion mutants of herpes simplex virus type 1 have a reduced capacity to reactivate following adrenergic induction in the rabbit eye model. We have mapped a reactivation phenotype within LAT and describe the construction of recombinants in which poly(A) addition sites have been placed at intervals within the LAT region to form truncated LAT transcripts. These mutants localize the induced reactivation phenotype to the 5 end of LAT. To further define this region, we constructed a recombinant containing a 348-bp deletion located 217 bp downstream of the transcription start site of the 8.5-kb LAT. This virus, 17⌬348, expresses LAT but exhibits a significantly reduced ability to reactivate following epinephrine iontophoresis into the cornea. Quantitative DNA PCR analysis reveals that 17⌬348 establishes a latent infection within rabbit trigeminal ganglia with the same efficiency as does either the rescuant or wild-type virus. The region deleted in 17⌬348 encodes three potential translational initiators (ATGs) which we have mutated and demonstrated to be dispensable for epinephrine-induced reactivation. In addition, three smaller deletions within this region have been constructed and were shown to reactivate at wild-type (parent) frequencies. These studies indicate that an undefined portion of the 348-bp region is required to facilitate induced reactivation. Sequence analysis of this 348-bp region revealed a CpG island which extends into the LAT promoter and which possesses homology to conserved elements within the mouse and human XIST transcript encoded on the X chromosome. Possible implications of these elements in the regulation of LAT expression are discussed.

show abstract

Section: Discussionsupporting

confidence: 53%

Section: Discussionmentioning

confidence: 99%

A 348-base-pair region in the latency-associated transcript facilitates herpes simplex virus type 1 reactivation

Bloom

Hill

Devi-Rao

et al. 1996

J Virol

102

View full text Add to dashboard Cite

show abstract

“…The translational frames which have been specifically mutagenized in this strain and shown to play no role in the efficient reactivation phenotypes in rabbits are shown as heavy bars in parentheses (17,74). Other translational frames in the 5Ј and other portions of LAT can be eliminated as playing a role based on data obtained by using inserted transcription termination/polyadenylation signals and by constructing deletions with other strains of virus (17,72,207). Finally, translation frames B, O, and P have been excluded from playing a major role in viral pathogenesis by specific mutagenesis (146).…”

Section: Detailed Characterization Of Latsmentioning

confidence: 99%

“…The prominent open translational reading frame within the HSV-1 LAT intron prompted speculation and experimental study of the possibility that it or another protein expressed during the latent phase of infection could mediate the reactivation phenotype (300). The expression of this open reading frame during productive infection has been detected (160,224), but its elimination by mutation has no effect upon efficient spontaneous or induced reactivation in rabbits (16,74), nor does such mutation have an effect on explant-induced recovery of virus from latently infected mouse neurons (72).…”

Section: There Is No Evidence For a Latent Phase-expressed Viral Protmentioning

confidence: 99%

Experimental investigation of herpes simplex virus latency

1997

View full text Add to dashboard Cite

The clinical manifestations of herpes simplex virus infection generally involve a mild and localized primary infection followed by asymptomatic (latent) infection interrupted sporadically by periods of recrudescence (reactivation) where virus replication and associated cytopathologic findings are manifest at the site of initial infection. During the latent phase of infection, viral genomes, but not infectious virus itself, can be detected in sensory and autonomic neurons. The process of latent infection and reactivation has been subject to continuing investigation in animal models and, more recently, in cultured cells. The initiation and maintenance of latent infection in neurons are apparently passive phenomena in that no virus gene products need be expressed or are required. Despite this, a single latency-associated transcript (LAT) encoded by DNA encompassing about 6% of the viral genome is expressed during latent infection in a minority of neurons containing viral DNA. This transcript is spliced, and the intron derived from this splicing is stably maintained in the nucleus of neurons expressing it. Reactivation, which can be induced by stress and assayed in several animal models, is facilitated by the expression of LAT. Although the mechanism of action of LAT-mediated facilitation of reactivation is not clear, all available evidence argues against its involving the expression of a protein. Rather, the most consistent models of action involve LAT expression playing a cis-acting role in a very early stage of the reactivation process.

show abstract

“…Thomas et al (84) demonstrated that deregulation of this major LAT ORF increased the growth potential of HSV-1 ICP0deficient mutant viruses. While these results all point to a protein encoded by LAT and its importance in virus regulation, Fareed and Spivack (27) showed that virus with defined mutations in the putative LAT ORFs did not differ from the parental wild-type virus in either the rate or frequency of reactivation. To further investigate the possibility of protein involvement in HSV-1 latency, Drolet et al (23) constructed recombinants between high-and low-frequency reactivation HSV-1 and found that the efficiency of reactivation was independent of the LAT ORF.…”

Section: Alphaherpesvirus Genes Transcribed During Latencymentioning

confidence: 88%

Human Herpesvirus Latency

Cohrs¹,

Gilden

2001

Brain Pathology

View full text Add to dashboard Cite

Herpesviruses are among the most successful human pathogens. In healthy individuals, primary infection is most often inapparent. After primary infection, the virus becomes latent in ganglia or blood mononuclear cells. Three major subfamilies of herpesviruses have been identified based on similar growth characteristics, genomic structure, and tissue predilection. Each herpesvirus has evolved its own unique ecological niche within the host that allows the maintenance of latency over the life of the individual (e.g. the adaptation to specific cell types in establishing latent infection and the mechanisms, including expression of different sets of genes, by which the virus remains latent). Neurotropic alphaherpesviruses become latent in dorsal root ganglia and reactivate to produce epidermal ulceration, either localized (herpes simplex types 1 and 2) or spread over several dermatomes (varicalla-zoster virus). Human cytomegalovirus, the prototype betaherpesvirus, establishes latency in bone marrow-derived myeloid progenitor cells. Reactivation of latent virus is especially serious in transplant recipients and AIDS patients. Lymphotropic gammaherpesviruses (Epstein-Barr virus) reside latent in resting B cells and reactivate to produce various neurologic complications. This review highlights the alphaherpesvirus, specifically herpes simplex virus type 1 and varicella-zoster virus, and describes the characteristics of latent infection.

show abstract

Two open reading frames (ORF1 and ORF2) within the 2.0-kilobase latency-associated transcript of herpes simplex virus type 1 are not essential for reactivation from latency

Cited by 30 publications

References 69 publications

A 348-base-pair region in the latency-associated transcript facilitates herpes simplex virus type 1 reactivation

A 348-base-pair region in the latency-associated transcript facilitates herpes simplex virus type 1 reactivation

Experimental investigation of herpes simplex virus latency

Human Herpesvirus Latency

Contact Info

Product

Resources

About