Sequence Variability in Clinical and Laboratory Isolates of Herpes Simplex Virus 1 Reveals New Mutations

Szpara, Moriah L.; Parsons, Lance; Enquist, Lynn W.

doi:10.1128/jvi.00312-10

Cited by 144 publications

(176 citation statements)

References 85 publications

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“…Both genes also exhibit some variation in other HSV-1 strains. Compared to strain 17, the deduced US8A proteins of the clinical isolate H129 and of strain HF10 exhibit one and four amino acid substitutions, respectively (McGeoch et al, 1985;Szpara et al, 2010;Ushijima et al, 2007). Likewise, the US9 proteins of HSV-1 strains 17 and HF10, and of isolate H129 differ at one or two positions.…”

Section: Us9 and Us8a Mutations In Hsv-1 Kosmentioning

confidence: 99%

Herpes simplex virus type 1 strain KOS carries a defective US9 and a mutated US8A gene

Negatsch

Mettenleiter

Fuchs

2010

Journal of General Virology

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The membrane protein encoded by the US9 gene of alphaherpesviruses plays an important role during virion assembly and transport in neurons. Here, we demonstrate that in herpes simplex virus type 1 (HSV-1) strain KOS, due to base substitutions, the predicted TATA-box of US9 is mutated, and a premature stop is present at codon 58 of US9, which contains 91 codons in other HSV-1 strains. The TATA-box mutation also removes the native stop codon of the adjacent US8A gene, leading to extension of the coding region from 160 to 191 codons. Northern blot analyses revealed reduced transcription of US9 in cells infected with HSV-1 KOS. Moreover, a US9-specific antiserum did not detect any gene products in Western blot and immunofluorescence analyses of KOS-infected cells, indicating that the truncated protein is not stable. In contrast, Western blot reactions of a pUS8A-specific antiserum confirmed enlargement of this protein in HSV-1 KOS.

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Section: Us9 and Us8a Mutations In Hsv-1 Kosmentioning

confidence: 99%

Herpes simplex virus type 1 strain KOS carries a defective US9 and a mutated US8A gene

Negatsch

Mettenleiter

Fuchs

2010

Journal of General Virology

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“…The complete genome of the HSV-1 laboratory strain 17 was determined in 1988 (5), and a large panel of HSV-1 genomes was recently sequenced (6,7). Analysis of this large panel of HSV-1 genomes from several geographically distinct regions (6) has shown that despite high levels of sequence conservation, HSV-1 strains exhibit interstrain diversity, as well as geographic clustering (6).…”

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confidence: 99%

Genome Sequencing and Analysis of Geographically Diverse Clinical Isolates of Herpes Simplex Virus 2

Newman

Lamers²,

Weiner

et al. 2015

J Virol

100

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Herpes simplex virus 2 (HSV-2), the principal causative agent of recurrent genital herpes, is a highly prevalent viral infection worldwide. Limited information is available on the amount of genomic DNA variation between HSV-2 strains because only two genomes have been determined, the HG52 laboratory strain and the newly sequenced SD90e low-passage-number clinical isolate strain, each from a different geographical area. In this study, we report the nearly complete genome sequences of 34 HSV-2 lowpassage-number and laboratory strains, 14 of which were collected in Uganda, 1 in South Africa, 11 in the United States, and 8 in Japan. Our analyses of these genomes demonstrated remarkable sequence conservation, regardless of geographic origin, with the maximum nucleotide divergence between strains being 0.4% across the genome. In contrast, prior studies indicated that HSV-1 genomes exhibit more sequence diversity, as well as geographical clustering. Additionally, unlike HSV-1, little viral recombination between HSV-2 strains could be substantiated. These results are interpreted in light of HSV-2 evolution, epidemiology, and pathogenesis. Finally, the newly generated sequences more closely resemble the low-passage-number SD90e than HG52, supporting the use of the former as the new reference genome of HSV-2. IMPORTANCEHerpes simplex virus 2 (HSV-2) is a causative agent of genital and neonatal herpes. Therefore, knowledge of its DNA genome and genetic variability is central to preventing and treating genital herpes. However, only two full-length HSV-2 genomes have been reported. In this study, we sequenced 34 additional HSV-2 low-passage-number and laboratory viral genomes and initiated analysis of the genetic diversity of HSV-2 strains from around the world. The analysis of these genomes will facilitate research aimed at vaccine development, diagnosis, and the evaluation of clinical manifestations and transmission of HSV-2. This information will also contribute to our understanding of HSV evolution. Herpes simplex virus 1 (HSV-1) and herpes simplex virus 2 (HSV-2) are two closely related human species of herpesviruses in the genus Simplexvirus of the family Herpesviridae (1). HSV-1 is mostly associated with orofacial infections, while HSV-2 is generally associated with genital herpes. Both viruses cause significant human disease, so knowledge of the structure of their DNA genomes and the extent of their genetic variation is very important. A high overall GC content and the presence of highly reiterated repeat regions in both noncoding and coding portions of the genome complicate sequence determination (2).The HSV linear double-stranded DNA genomes consist of two covalent linked components, the long (L) and short (S) components, which invert relative to each other by intramolecular recombination (1). The L component consists of unique sequences (U L ) bounded by inverted repeats (R L and R L =), and the S component consists of unique sequences (U S ) bounded by inverted repeats (R S and R S =) (3). The termini con...

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“…The TK mutation observed occurred in eight clones, suggesting that it might provide some selective advantage in the course of the transfers in 143 TK 2 cells (Table 1). The HSV-1 genomic regions (belonging to the polymerase, glycoprotein gD and thymidine kinase genes) used to sample the presence of mutations in HSV-1 clones, were chosen because they represent structural and non-structural, as well as dispensable and essential genes (McGeoch et al, 2008;Roizman et al, 2007;Szpara et al, 2010). They should mirror the entire HSV-1 genome in terms of point mutation acquisition because in a comparison of strains 17, H129 and F, mutations were distributed along the entire coding-region, and the number of substitutions in the DNA polymerase, glycoprotein D and thymidine kinase did not differ significantly from the average for all encoded proteins (Szpara et al, 2010).…”

Section: Discussionmentioning

confidence: 99%

“…1 ). Considering that the HSV-1 genome has 152 400 bp (Szpara et al, 2010), and assuming that the number of mutations found reflects the average number of mutations per genome, the HSV-1 clones subjected to multiple plaque-to-plaque transfers accumulated an average of 54.62 mutations per genome (confidence interval 99 %: 20.31-116.86). Since the average number of transfers undergone by the 23 HSV-1 clones that have been analysed by nucleotide sequencing is 9.6 ( Fig.…”

Section: Mutation Frequencies In Different Hsv-1 Genomic Regionsmentioning

confidence: 99%

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Evidence of Muller’s ratchet in herpes simplex virus type 1

Jaramillo

Domingo

Múñoz-Egea

et al. 2013

Journal of General Virology

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Population bottlenecks can have major effects in the evolution of RNA viruses, but their possible influence in the evolution of DNA viruses is largely unknown. Genetic and biological variation of herpes simplex virus type 1 (HSV-1) has been studied by subjecting 23 biological clones of the virus to 10 plaque-to-plaque transfers. In contrast to large population passages, plaque transfers led to a decrease in replicative capacity of HSV-1. Two out of a total of 23 clones did not survive to the last transfer in 143 TK -cells. DNA from three genomic regions (DNA polymerase, glycoprotein gD and thymidine kinase) from the initial and passaged clones was sequenced. Nucleotide substitutions were detected in the TK and gD genes, but not in the DNA polymerase gene. Assuming a uniform distribution of mutations along the genome, the average rate of fixation of mutations was about five mutations per viral genome and plaque transfer. This value is comparable to the range of values calculated for RNA viruses. Four plaque-transferred populations lost neurovirulence for mice, as compared with the corresponding initial clones. LD 50 values obtained with the populations subjected to serial bottlenecks were 4-to 67-fold higher than for their parental clones. These results equate HSV-1 with RNA viruses regarding fitness decrease as a result of plaque-to-plaque transfers, and show that population bottlenecks can modify the pathogenic potential of HSV-1. Implications for the evolution of complex DNA viruses are discussed. INTRODUCTIONThe concept that small asexual populations of organisms will tend to accumulate deleterious mutations unless genetic lesions are repaired by sex or recombination was first proposed by Muller (Muller, 1932, 1964 and is known as the Muller's ratchet hypothesis (Bell, 1988;Colato & Fontanari, 2001;Felsenstein, 1974;Maynard Smith, 1976;Nowak & Schuster, 1989). Its operation has found experimental confirmation mainly in studies carried out with RNA viruses (Chao, 1990; Clarke et al., 1993;de la Iglesia & Elena, 2007;Duarte et al., 1992Duarte et al., , 1994Escarmís et al., 1996Escarmís et al., , 2009Novella, 2004; Novella & EbendickCorpus, 2004; reviewed by Escarmís et al., 2006), and also with plants, protozoa, mitochondrial DNA and bacteria (Allen et al., 2009;Andersson & Hughes, 1996;Bell, 1988;Coates, 1992; Engelstädter, 2008;Loewe, 2006;Moran, 1996). The effects of Muller's ratchet are accentuated when an asexual genome population undergoes severe bottleneck events. In the case of RNA viruses, mutation rates in the range of 10 23 to 10 25 substitutions per nucleotide copied (Batschelet et al., 1976;Domingo et al., 1996Domingo et al., , 2006Drake & Holland, 1999; Sanjuán et al., 2010) dictate that 0.1 to 10 mutations will occur upon synthesis of any new genomic molecule in an infected cell. Generally, the frequency of deleterious mutations is on average higher than the frequency of beneficial mutations. In consequence, the random sampling of a genome from a population to give rise to a new plaque on a cell...

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Sequence Variability in Clinical and Laboratory Isolates of Herpes Simplex Virus 1 Reveals New Mutations

Cited by 144 publications

References 85 publications

Herpes simplex virus type 1 strain KOS carries a defective US9 and a mutated US8A gene

Herpes simplex virus type 1 strain KOS carries a defective US9 and a mutated US8A gene

Genome Sequencing and Analysis of Geographically Diverse Clinical Isolates of Herpes Simplex Virus 2

Evidence of Muller’s ratchet in herpes simplex virus type 1

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