Analysis of intrastrain recombination in herpes simplex virus type 1 strain 17 and herpes simplex virus type 2 strain HG52 using restriction endonuclease sites as unselected markers and temperature-sensitive lesions as selected markers

Sm, Brown; Jh, Subak-Sharpe; Harland, J; Ar, MacLean

doi:10.1099/0022-1317-73-2-293

Cited by 28 publications

(22 citation statements)

References 16 publications

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“…The replication of HSV-1 DNA is closely associated with homologous recombination (48). Through the use of strains with different markers, HSV-1 recombinants have frequently been detected in cell culture systems (5,17,47). After coinfection of different HSV-1 strains in heterologous animal models, recombination has readily been identified (21,50).…”

Section: Discussionmentioning

confidence: 99%

Phylogenetic Analysis of Clinical Herpes Simplex Virus Type 1 Isolates Identified Three Genetic Groups and Recombinant Viruses

Norberg

Bergström

Rekabdar

et al. 2004

J Virol

148

192

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Herpes simplex virus type 1 (HSV-1) is a ubiquitous human pathogen which establishes lifelong infections. In the present study, we determined the sequence diversity of the complete genes coding for glycoproteins G (gG), I (gI), and E (gE), comprising 2.3% of the HSV-1 genome and located within the unique short (US) region, for 28 clinical HSV-1 isolates inducing oral lesions, genital lesions, or encephalitis. Laboratory strains F and KOS321 were sequenced in parallel. Phylogenetic analysis, including analysis of laboratory strain 17 (GenBank), revealed that the sequences were separated into three genetic groups. The identification of different genogroups facilitated the detection of recombinant viruses by using specific nucleotide substitutions as recombination markers. Seven of the isolates and strain 17 displayed sequences consistent with intergenic recombination, and at least four isolates were intragenic recombinants. The observed frequency of recombination based on an analysis of a short stretch of the US region suggests that most full-length HSV-1 genomes consist of a mosaic of segments from different genetic groups. Polymorphic tandem repeat regions, consisting of two to eight blocks of 21 nucleotides in the gI gene and seven to eight repeats of 3 nucleotides in the gG gene, were also detected. Laboratory strain KOS321 displayed a frameshift mutation in the gI gene with a subsequent alteration of the deduced intracellular portion of the protein. The presence of polymorphic tandem repeat regions and the different genogroup identities can be used for molecular epidemiology studies and for further detection of recombination in the HSV-1 genome.The family Herpesviridae is a large family comprising at least 100 herpesviruses which are highly disseminated among animals. Eight human herpesviruses have been described, and molecular phylogenetic analysis has established three subfamilies (24). These three groups correspond to the current taxonomic classification based on biological properties and include the Alphaherpesvirinae, Betaherpesvirinae, and Gammaherpesvirinae. Herpes simplex virus (HSV) belongs to the Alphaherpesvirinae and is classified in this subfamily on the basis of a wide host cell range, an efficient and rapid reproductive cell cycle, and the capacity to establish latency in the sensory ganglia (38).A major mechanism which upholds the accuracy of replication involves the 3Ј35Ј-exonuclease activity associated with DNA polymerases. Proofreading activity has been demonstrated for the HSV type 1 (HSV-1) DNA polymerase (1). In addition, it is likely that cellular repair mechanisms contribute to the stability of the virus genome. The overall mutation rate for HSV-1 has been estimated to be 3.5 ϫ 10 Ϫ8 mutations/site/ year (41), and the genome is therefore more stable than that described for RNA viruses (13, 18). Although genetic variations and classification into different genogroups have been described for other herpesviruses, such as varicella-zoster virus (31), Epstein-Barr virus (42), cytomegaloviru...

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Section: Discussionmentioning

confidence: 99%

Phylogenetic Analysis of Clinical Herpes Simplex Virus Type 1 Isolates Identified Three Genetic Groups and Recombinant Viruses

Norberg

Bergström

Rekabdar

et al. 2004

J Virol

148

192

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“…Using this approach, previous studies have reported the relationship of recombination frequencies and map distances between marker loci, and t Present address: Skin Research Department, Unilever Corporation, 45 River Road. Edgewater, New Jersey 07020, U.S.A. potential mechanisms of herpesviral recombination (BenPorat et al, 1982;Ihara et al, 1982;Brown et al, 1992). It seems unlikely that natural recombination would occur in vivo under conditions of high m.o.i, with synchronous infection of all available target cells by both parental virus strains.…”

Section: Introductionmentioning

confidence: 99%

Genetic recombination between two strains of Aujeszky's disease virus at reduced multiplicity of infection

Dangler

Deaver

Kolodziej

1994

Journal of General Virology

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The potential for in vivo genetic recombination has been suggested for Aujeszky's disease virus (ADV) stemming from the use of modified-live vaccines carrying vaccinespecific deletion mutations. This scenario serves as a model for the study of biological factors that affect in vivo herpesviral recombination and, ultimately, the natural evolution of herpesviruses. This report describes experiments evaluating the efficiency of ADV recombination under in vitro conditions of low multiplicity infection which were felt to represent in vivo conditions more closely than previous in vitro measurements of ADV recombination. A series of experiments were performed to measure in vitro recovery of recombinant viral progeny following co-infection of cell monolayers with nonsaturating concentrations of two parental strains of ADV. A simple statistical model was generated to estimate the rate of cellular co-infection. After a single replicative cycle infectious viral progeny were recovered and their genotypes determined at two alleles by characterization of two gene loci using a battery of PCR assays. Recovery rates of parental and recombinant progeny genotypes were calculated from the PCR data. The observed frequency of recovery of recombinant viral progeny closely approximated the values projected by the model calculations. The data from our system suggest that at low multiplicity of infection, the rate of genetic recombination is a function of the probability of cellular co-infection.

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“…Electron micrographs have revealed that replication intermediates are branched and contain Y-and X-shaped junctions (19,52). Furthermore, high levels of recombination have been reported not only between coinfecting viral strains (4,17,50,62,66) but also in plasmids containing repeated sequence elements (10,11). These observations, taken together, are not consistent with a simple rolling circle mechanism of replication and suggest that, reminiscent of the bacteriophages T4 and lambda, HSV-1 utilizes a recombination-dependent replication mechanism to generate concatemeric viral DNA.…”

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confidence: 99%

Physical Interaction between the Herpes Simplex Virus Type 1 Exonuclease, UL12, and the DNA Double-Strand Break-Sensing MRN Complex

Balasubramanian

Bai

Buchek

et al. 2010

J Virol

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The herpes simplex virus type 1 (HSV-1) alkaline nuclease, encoded by the UL12 gene, plays an important role in HSV-1 replication, as a UL12 null mutant displays a severe growth defect. The HSV-1 alkaline exonuclease UL12 interacts with the viral single-stranded DNA binding protein ICP8 and promotes strand exchange in vitro in conjunction with ICP8. We proposed that UL12 and ICP8 form a two-subunit recombinase reminiscent of the phage lambda Red ␣/␤ recombination system and that the viral and cellular recombinases contribute to viral genome replication through a homologous recombination-dependent DNA replication mechanism. To test this hypothesis, we identified cellular interaction partners of UL12 by using coimmunoprecipitation. We report for the first time a specific interaction between UL12 and components of the cellular MRN complex, an important factor in the ATM-mediated homologous recombination repair (HRR) pathway. This interaction is detected early during infection and does not require viral DNA or other viral or cellular proteins. The region of UL12 responsible for the interaction has been mapped to the first 125 residues, and coimmunoprecipitation can be abolished by deletion of residues 100 to 126. These observations support the hypothesis that cellular and viral recombination factors work together to promote efficient HSV-1 growth.The herpes simplex virus (HSV) genome replicates in the nucleus of an infected host cell, resulting in the production of longer-than-unit-length head-to-tail concatemers of viral DNA. Production of infectious virus requires the processing of concatemeric DNA into unit-length genomes by the packaging machinery followed by encapsidation into preassembled capsids (63). Several lines of evidence suggest that recombination plays a role in concatemer formation (69). Genomic inversions, proposed to occur through recombination, can be detected very early during infection, and these inversions require sequence homology (2,23,56). In addition, replication intermediates in HSV type 1 (HSV-1)-infected cells adopt a complex nonlinear structure that does not migrate in a pulsed-field gel, even after digestion with an enzyme that cuts once per unit length of the genome (1,33,51,71). Electron micrographs have revealed that replication intermediates are branched and contain Y-and X-shaped junctions (19,52). Furthermore, high levels of recombination have been reported not only between coinfecting viral strains (4, 17, 50, 62, 66) but also in plasmids containing repeated sequence elements (10, 11). These observations, taken together, are not consistent with a simple rolling circle mechanism of replication and suggest that, reminiscent of the bacteriophages T4 and lambda, HSV-1 utilizes a recombination-dependent replication mechanism to generate concatemeric viral DNA.We have previously reported that virus-encoded proteins are capable of participating in recombination events in vitro. The viral 5Ј-3Ј alkaline exonuclease (UL12) and the single-strand binding protein (ICP8) together mediate stra...

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Analysis of intrastrain recombination in herpes simplex virus type 1 strain 17 and herpes simplex virus type 2 strain HG52 using restriction endonuclease sites as unselected markers and temperature-sensitive lesions as selected markers

Cited by 28 publications

References 16 publications

Phylogenetic Analysis of Clinical Herpes Simplex Virus Type 1 Isolates Identified Three Genetic Groups and Recombinant Viruses

Phylogenetic Analysis of Clinical Herpes Simplex Virus Type 1 Isolates Identified Three Genetic Groups and Recombinant Viruses

Genetic recombination between two strains of Aujeszky's disease virus at reduced multiplicity of infection

Physical Interaction between the Herpes Simplex Virus Type 1 Exonuclease, UL12, and the DNA Double-Strand Break-Sensing MRN Complex

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