Study of the Structure of Replicative Intermediates of HSV-1 DNA by Pulsed-Field Gel Electrophoresis

Severini, Alberto; Morgan, A R; Tovell, Dorothy R.; Tyrrell, D. L. J.

doi:10.1006/viro.1994.1206

Cited by 89 publications

(114 citation statements)

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“…It has previously been shown that during herpesvirus DNA packaging only the genomic terminus containing the pac2 signal is found associated with the high-molecular-weight concatemeric DNA (15,17,19,25,26,36), and this observation has formed the basis for a proposal that the pac2 sequence controls the initiation and directionality of DNA packaging (19). Our observations that mutations within pac2 have relatively greater effects during the first cycle of infection and that motifs in pac1 may be involved in the late stages of DNA encapsidation are compatible with this model.…”

Section: Discussionmentioning

confidence: 99%

Effects of Mutations within the Herpes Simplex Virus Type 1 DNA Encapsidation Signal on Packaging Efficiency

Hodge¹,

Stow²

2001

J Virol

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The cis-acting signals required for cleavage and encapsidation of the herpes simplex virus type 1 genome lie within the terminally redundant region or a sequence. The a sequence is flanked by short direct repeats (DR1) containing the site of cleavage, and quasi-unique regions, Uc and Ub, occupy positions adjacent to the genomic L and S termini, respectively, such that a novel fragment, Uc-DR1-Ub, is generated upon ligation of the genomic ends. The Uc-DR1-Ub fragment can function as a minimal packaging signal, and motifs have been identified within Uc and Ub that are conserved near the ends of other herpesvirus genomes (pac2 and pac1, respectively). We have introduced deletion and substitution mutations within the pac regions of the Uc-DR1-Ub fragment and assessed their effects on DNA packaging in an amplicon-based transient transfection assay. Within pac2, mutations affecting the T tract had the greatest inhibitory effect, but deletion of sequences on either side of this element also reduced packaging, suggesting that its position relative to other sequences within the Uc-DR1-Ub fragment is likely to be important. No single region essential for DNA packaging was detected within pac1. However, mutants lacking the G tracts on either side of the pac1 T-rich motif exhibited a reduced efficiency of serial propagation, and alteration of the sequences between DR1 and the pac1 T element also resulted in defective generation of Ub-containing terminal fragments. The data are consistent with a model in which initiation and termination of packaging are specified by sequences within Uc and Ub, respectively.Herpesviruses have linear double-stranded DNA genomes of 125 to 245 kbp that are circularized upon infection and replicate in an "endless" form, generating branched concatemeric structures. During the assembly of progeny particles, the concatemers are cleaved at specific sites corresponding to the genomic termini and, in a tightly coupled process, the viral DNA is packaged into preformed capsids (reviewed in references 13, 20, and 23).In the case of herpes simplex virus type 1 (HSV-1), the cis-acting sequences required for cleavage and packaging reside within the terminally redundant region or a sequence (21,29,32,34). The a sequence is 250 to 500 bp long and present as a single copy at the S terminus and one or more tandem copies at the L terminus. In addition, one or more copies are also present in inverted orientation at the junction between the L and S segments (23).Flanking the a sequences are direct repeats (DR1) of 17 to 20 bp, with single copies of DR1 separating tandem a sequences. The site of genomic cleavage occurs within the DR1 element such that a single copy is regenerated upon ligation of the two genomic ends (see Fig. 1). The central portion of the a sequence comprises multiple tandem reiterations of one or two other short sequence elements (11 to 24 bp) referred to as DR2 and DR4. The quasi-unique sequences, each of ca. 80 bp, which lie between DR1 and either side of the DR2 and DR4 repeats are termed the ...

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Section: Discussionmentioning

confidence: 99%

Effects of Mutations within the Herpes Simplex Virus Type 1 DNA Encapsidation Signal on Packaging Efficiency

Hodge¹,

Stow²

2001

J Virol

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“…The structure resulting from DNA replication is even more complex because it contains frequent branches. These branched structures are most likely generated by recombination and were observed in concatemeric DNA of HSV-1 [7,8,183,184] and BoHV-1 [181]. Another consequence of the recombination process was detected in BoHV-1 concatemeric DNA.…”

Section: Bohv-1 Replication In the Cellmentioning

confidence: 96%

Bovine herpesvirus 1 infection and infectious bovine rhinotracheitis

et al. 2007

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-Bovine herpesvirus 1 (BoHV-1), classified as an alphaherpesvirus, is a major pathogen of cattle. Primary infection is accompanied by various clinical manifestations such as infectious bovine rhinotracheitis, abortion, infectious pustular vulvovaginitis, and systemic infection in neonates. When animals survive, a life-long latent infection is established in nervous sensory ganglia. Several reactivation stimuli can lead to viral re-excretion, which is responsible for the maintenance of BoHV-1 within a cattle herd. This paper focuses on an updated pathogenesis based on a molecular characterization of BoHV-1 and the description of the virus cycle. Special emphasis is accorded to the impact of the latency and reactivation cycle on the epidemiology and the control of BoHV-1. Several European countries have initiated BoHV-1 eradication schemes because of the significant losses incurred by disease and trading restrictions. The vaccines used against BoHV-1 are described in this context where the differentiation of infected from vaccinated animals is of critical importance to achieve BoHV-1 eradication.

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“…The 11 HSV-1 early genes encode enzymes that replicate virus DNA in two stages: first by h replication (Severini et al, 1994) followed by a s (rolling circle) mechanism (Skaliter et al, 1996). Transcription of the third class of HSV-1 genes reaches its peak after virus DNA replication has begun (Wagner et al, 1998).…”

Section: Fate Of Incoming Dnamentioning

confidence: 99%

A comparison of herpes simplex virus type 1 and varicella-zoster virus latency and reactivation

Kennedy

Rovnak

Badani

et al. 2015

Journal of General Virology

133

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Herpes simplex virus type 1 (HSV-1; human herpesvirus 1) and varicella-zoster virus (VZV; human herpesvirus 3) are human neurotropic alphaherpesviruses that cause lifelong infections in ganglia. Following primary infection and establishment of latency, HSV-1 reactivation typically results in herpes labialis (cold sores), but can occur frequently elsewhere on the body at the site of primary infection (e.g. whitlow), particularly at the genitals. Rarely, HSV-1 reactivation can cause encephalitis; however, a third of the cases of HSV-1 encephalitis are associated with HSV-1 primary infection. Primary VZV infection causes varicella (chickenpox) following which latent virus may reactivate decades later to produce herpes zoster (shingles), as well as an increasingly recognized number of subacute, acute and chronic neurological conditions. Following primary infection, both viruses establish a latent infection in neuronal cells in human peripheral ganglia. However, the detailed mechanisms of viral latency and reactivation have yet to be unravelled. In both cases latent viral DNA exists in an 'end-less' state where the ends of the virus genome are joined to form structures consistent with unit length episomes and concatemers, from which viral gene transcription is restricted. In latently infected ganglia, the most abundantly detected HSV-1 RNAs are the spliced products originating from the primary latency associated transcript (LAT). This primary LAT is an 8.3 kb unstable transcript from which two stable (1.5 and 2.0 kb) introns are spliced. Transcripts mapping to 12 VZV genes have been detected in human ganglia removed at autopsy; however, it is difficult to ascribe these as transcripts present during latent infection as early-stage virus reactivation may have transpired in the post-mortem time period in the ganglia. Nonetheless, low-level transcription of VZV ORF63 has been repeatedly detected in multiple ganglia removed as close to death as possible. There is increasing evidence that HSV-1 and VZV latency is epigenetically regulated. In vitro models that permit pathway analysis and identification of both epigenetic modulations and global transcriptional mechanisms of HSV-1 and VZV latency hold much promise for our future understanding in this complex area. This review summarizes the molecular biology of HSV-1 and VZV latency and reactivation, and also presents future directions for study. Received 5 January 2015Accepted 18 March 2015 IntroductionHerpes simplex virus type 1 (HSV-1; human herpesvirus 1) and varicella-zoster virus (VZV; human herpesvirus 3) are human neurotropic alphaherpesviruses usually acquired early in life. Primary HSV-1 infection is usually localized and may be asymptomatic, although it can produce a more widespread systemic infection in neonates and immunocompromised adults, whilst primary VZV infection is systemic and results in childhood varicella (chickenpox). During primary infection, both viruses gain access to neurons most likely through retrograde transport from the site of cutaneous lesion...

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Study of the Structure of Replicative Intermediates of HSV-1 DNA by Pulsed-Field Gel Electrophoresis

Cited by 89 publications

References 0 publications

Effects of Mutations within the Herpes Simplex Virus Type 1 DNA Encapsidation Signal on Packaging Efficiency

Effects of Mutations within the Herpes Simplex Virus Type 1 DNA Encapsidation Signal on Packaging Efficiency

Bovine herpesvirus 1 infection and infectious bovine rhinotracheitis

A comparison of herpes simplex virus type 1 and varicella-zoster virus latency and reactivation

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