Variations of HSV-1 Glycoprotein B in Human Herpes Simplex Encephalitis

Sivadon, V.; Lebon, Pierre; Rozenberg, Flore

doi:10.3109/13550289809113488

Cited by 18 publications

(11 citation statements)

References 41 publications

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“…Absence of gB results in loss of infectivity, as observed in cell culture, and after infection of primary target cells in vivo by phenotypically complemented mutant virus, viral spread does not occur (1,31,33,37). Mutations in the cytoplasmic domain of gB resulting in a syncytial phenotype profoundly influence pathogenesis in vivo (7,10,42,45). We show here that exchange of PrV gB by the homologous BHV-1 gB resulted in a dramatic increase in neurovirulence.…”

Section: Discussionmentioning

confidence: 73%

Pseudorabies Virus Expressing Bovine Herpesvirus 1 Glycoprotein B Exhibits Altered Neurotropism and Increased Neurovirulence

Gerdts¹,

Beyer

Lomniczi

et al. 2000

J Virol

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Herpesvirus glycoproteins play dominant roles in the initiation of infection of target cells in culture and thus may also influence viral tropism in vivo. Whereas the relative contribution of several nonessential glycoproteins to neurovirulence and neurotropism of Pseudorabies virus (PrV), an alphaherpesvirus which causes Aujeszky's disease in pigs, has recently been uncovered in studies using viral deletion mutants, the importance of essential glycoproteins is more difficult to assess. We isolated an infectious PrV mutant, PrV-9112C2, which lacks the gene encoding the essential PrV glycoprotein B (gB) but stably carries in its genome and expresses the homologous gene of bovine herpesvirus 1 (BHV-1) (A. Kopp and T. C. Mettenleiter, J. Virol. 66:2754-2762, 1992). Apart from exhibiting a slight delay in penetration kinetics, PrV-9112C2 was similar in its growth characteristics in cell culture to wild-type PrV. To analyze the effect of the exchange of these homologous glycoproteins in PrV's natural host, swine, 4-week-old piglets were intranasally infected with 10 6 PFU of either wild-type PrV strain Kaplan (PrV-Ka), PrV-9112C2, or PrV-9112C2R, in which the PrV gB gene was reinserted instead of the BHV-1 gB gene. Animals infected with PrV-Ka and PrV-9112C2R showed a similar course of disease, i.e., high fever, marked respiratory symptoms but minimal neurological disorders, and excretion of high amounts of virus. All animals survived the infection. In contrast, animals infected with PrV-9112C2 showed no respiratory symptoms and developed only mild fever. However, on day 5 after infection, all piglets developed severe central nervous system (CNS) symptoms leading to death within 48 to 72 h. Detailed histological analyses showed that PrV-9112C2R infected all regions of the nasal mucosa and subsequently spread to the CNS preferentially by the trigeminal route. In contrast, PrV-9112C2 primarily infected the olfactory epithelium and spread via the olfactory route. In the CNS, more viral antigen and significantly more pronounced histological changes resulting in more severe encephalitis were found after PrV-9112C2 infection. Thus, our results demonstrate that replacement of PrV gB by the homologous BHV-1 glycoprotein resulted in a dramatic increase in neurovirulence combined with an alteration in the route of neuroinvasion, indicating that the essential gB is involved in determining neurotropism and neurovirulence of PrV.Pseudorabies virus (PrV) and Bovine herpesvirus 1 (BHV-1) are related alphaherpesviruses of the genus Varicellovirus. PrV, also designated Suid herpesvirus 1, is the causative agent of Aujeszky's disease (AD), a serious illness in domestic and wild animals. PrV has a broad host range and productively infects birds and most mammals, except for horses and higher primates including humans, which are resistant to infection (reviewed in reference 25). Whereas mortality in most infected species regularly amounts to 100%, pigs can survive a productive infection and remain latently infected for life. Thus, pigs a...

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Section: Discussionmentioning

confidence: 73%

Pseudorabies Virus Expressing Bovine Herpesvirus 1 Glycoprotein B Exhibits Altered Neurotropism and Increased Neurovirulence

Gerdts¹,

Beyer

Lomniczi

et al. 2000

J Virol

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“…In the present study, we were unable to find associations between specific sequences in the gG, gI, and gE genes and anatomical sites of lesions, including the brain. Previously published studies on the sequence variability of the glycoprotein B and D genes did not reveal mutations specific for HSV-1 DNA sequences amplified from cerebrospinal fluid samples from encephalitis patients (40,44). However, different reports have shown that clinical HSV-1 isolates differ in virulence when tested in animal models (3,11,37).…”

Section: Discussionmentioning

confidence: 97%

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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“…Genetic variability of this gene among clinical isolates may therefore be of importance for the immunoglobulin G (IgG) response within the individual host when a predefined gG-1 antigen is used for detection. Previously, a few studies have described a limited genetic variability of genes coding for envelope glycoprotein among HSV-1 strains as shown by DNA sequencing of the gB-gene (30) or the gD gene (27) after PCR amplification of cerebrospinal fluid samples. These studies observed some point mutations which were mostly silent, and the insertion or deletion of one or a few codons compared to a previously published HSV-1 sequence (21).…”

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confidence: 99%

Dichotomy of Glycoprotein G Gene in Herpes Simplex Virus Type 1 Isolates

Rekabdar¹,

Liljeqvist²,

Lindh³

et al. 2002

J Clin Microbiol

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Herpes simplex virus type 1 (HSV-1) encodes 11 envelope glycoproteins, of which glycoprotein G-1 (gG-1) induces a type-specific antibody response. Variability of the gG-1 gene among wild-type strains may be a factor of importance for a reliable serodiagnosis and typing of HSV-1 isolates. Here, we used a gG-1 type-specific monoclonal antibody (MAb) to screen for mutations in the immunodominant region of this protein in 108 clinical HSV-1 isolates. Of these, 42 isolates showed no reactivity to the anti-gG-1 MAb. One hundred five strains were further examined by DNA sequencing of the middle part of the gG-1 gene, encompassing 106 amino acids including the immunodominant region and epitope of the anti-gG-1 MAb. By phylogenetic comparisons based on the sequence data, we observed two (main) genetic variants of the gG-1 gene among the clinical isolates corresponding to reactivity or nonreactivity to the anti-gG-1 MAb. Furthermore, four strains appeared to be recombinants of the two gG-1 variants. In addition, one strain displayed a gG-1-negative phenotype due to a frameshift mutation, in the form of insertion of a cytosine nucleotide. When immunoglobulin G reactivity to HSV-1 in sera from patients infected with either of the two variants was investigated, no significant differences were found between the two groups, either in a type-common enzyme-linked immunosorbent assay (ELISA) or in a type-specific gG-1 antigen-based ELISA. Despite the here-documented existence of two variants of the gG-1 gene affecting the immunodominant region of the protein, other circumstances, such as early phase of infection, might be sought for explaining the seronegativity to gG-1 commonly found in a proportion of the HSV-1-infected patients.

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Variations of HSV-1 Glycoprotein B in Human Herpes Simplex Encephalitis

Cited by 18 publications

References 41 publications

Pseudorabies Virus Expressing Bovine Herpesvirus 1 Glycoprotein B Exhibits Altered Neurotropism and Increased Neurovirulence

Pseudorabies Virus Expressing Bovine Herpesvirus 1 Glycoprotein B Exhibits Altered Neurotropism and Increased Neurovirulence

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

Dichotomy of Glycoprotein G Gene in Herpes Simplex Virus Type 1 Isolates

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