Dataset Information

Disruption of the U(L)41 gene in the herpes simplex virus 2 dl5-29 mutant increases its immunogenicity and protective capacity in a murine model of genital herpes.

ABSTRACT: The herpes simplex virus 2 dl5-29 replication-defective mutant virus has been shown to induce protective immunity in mice and both prophylactic and therapeutic immunity in guinea pigs. In an attempt to improve the efficacy of dl5-29 we disrupted its U(L)41 gene, producing the triple mutant virus dl5-29-41L. dl5-29-41L has a decreased ability to inhibit host cell protein synthesis and a reduced cytopathic effect on cultured cells. When used to immunize mice, dl5-29-41L elicited significantly stronger neutralizing antibody responses and significantly stronger CD4(+) and CD8(+) cellular immune responses than dl5-29. The enhanced immune responses corresponded with increased protective capacity in a murine model of genital herpes. The protective immunity elicited by either virus was very durable, protecting mice for at least 7 months. Furthermore, we show that cell lysate preparations of both viruses were significantly more efficacious than the corresponding extracellular virus preparations.

SUBMITTER: Dudek T

PROVIDER: S-EPMC2323115 | biostudies-literature | 2008 Mar

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Disruption of the U(L)41 gene in the herpes simplex virus 2 dl5-29 mutant increases its immunogenicity and protective capacity in a murine model of genital herpes.

Dudek Timothy T Mathews Lydia C LC Knipe David M DM

Virology 20071119 1

The herpes simplex virus 2 dl5-29 replication-defective mutant virus has been shown to induce protective immunity in mice and both prophylactic and therapeutic immunity in guinea pigs. In an attempt to improve the efficacy of dl5-29 we disrupted its U(L)41 gene, producing the triple mutant virus dl5-29-41L. dl5-29-41L has a decreased ability to inhibit host cell protein synthesis and a reduced cytopathic effect on cultured cells. When used to immunize mice, dl5-29-41L elicited significantly stro ...[more]

PMID: 18006033

Similar Datasets

Project description:Genital herpes simplex virus (HSV) reactivation is thought to be anatomically and temporally localized, coincident with limited ganglionic infection. Short, subclinical shedding episodes are the most common form of HSV-2 reactivation, with host clearance mechanisms leading to rapid containment. The anatomic distribution of shedding episodes has not been characterized. To precisely define patterns of anatomic reactivation, we divided the genital tract into a 22-region grid and obtained daily swabs for 20 days from each region in 28 immunocompetent, HSV-2-seropositive persons. HSV was detected via PCR, and sites of asymptomatic HSV shedding were subjected to a biopsy procedure within 24 h. CD4(+) and CD8(+) T cells were quantified by immunofluorescence, and HSV-specific CD4(+) T cells were identified by intracellular cytokine cytometry. HSV was detected in 868 (7%) of 11,603 genital swabs at a median of 12 sites per person (range, 0 to 22). Bilateral HSV detection occurred on 83 (67%) days with shedding, and the median quantity of virus detected/day was associated with the number of sites positive (P < 0.001). In biopsy specimens of asymptomatic shedding sites, we found increased numbers of CD8(+) T cells compared to control tissue (27 versus 13 cells/mm(2), P = 0.03) and identified HSV-specific CD4(+) T cells. HSV reactivations emanate from widely separated anatomic regions of the genital tract and are associated with a localized cellular infiltrate that was demonstrated to be HSV specific in 3 cases. These data provide evidence that asymptomatic HSV-2 shedding contributes to chronic inflammation throughout the genital tract.This detailed report of the anatomic patterns of genital HSV-2 shedding demonstrates that HSV-2 reactivation can be detected at multiple bilateral sites in the genital tract, suggesting that HSV establishes latency throughout the sacral ganglia. In addition, genital biopsy specimens from sites of asymptomatic HSV shedding have increased numbers of CD8(+) T cells compared to control tissue, and HSV-specific CD4(+) T cells are found at sites of asymptomatic shedding. These findings suggest that widespread asymptomatic genital HSV-2 shedding is associated with a targeted host immune response and contributes to chronic inflammation throughout the genital tract.

Dataset Information

Disruption of the U(L)41 gene in the herpes simplex virus 2 dl5-29 mutant increases its immunogenicity and protective capacity in a murine model of genital herpes.

Publications

Disruption of the U(L)41 gene in the herpes simplex virus 2 dl5-29 mutant increases its immunogenicity and protective capacity in a murine model of genital herpes.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets