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

Abstract

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...

Natural Recombinant between Equine Herpesviruses 1 and 4 in the ICP4 Gene

“…2. lation as one of dominant virus species. Hitherto intraspecies recombinants have been reported including HSV-1, VZV, and EBV (22)(23)(24)38). On the other hand, interspecies recombinants have been regarded to survive rarely in nature (5).…”

Pattern recognition receptors in microbial keratitis

“…Of note when considering the mechanism of HSV1 infection is the fact that phylogenetic analysis suggests the evolution of at least six distinct HSV1 genogroups, with multiple recombination events detected in the genome coding for glycoproteins. 137,138 The high mutation rate of such viral proteins provides an additional challenge when aiming to identify targeted and/or personalised therapeutic options.…”

Ancient recombination events between human herpes simplex viruses

“…Yet, the recombinant fragments in UL29 and UL30 went unnoticed, albeit being present in all partial and complete genomes published prior to our study. We note here that early studies focused on recombination used PCR-based approaches and typically covered 2-4% of the genome; to our knowledge, they did not target any of the coding sequences in which we identified recombinant HSV-1 fragments (Bowden et al 2004;Norberg et al 2004Norberg et al , 2007. More recently, a number of studies have produced several dozens of HSV-1 and HSV-2 complete (or nearly complete) genomes which were used to examine genome-wide patterns of recombination (Kolb et al 2011(Kolb et al , 2013(Kolb et al , 2015Szpara et al 2014;Newman et al 2015).…”