Induction of Potent Humoral and Cell-Mediated Immune Responses by Attenuated Vaccinia Virus Vectors with Deleted Serpin Genes

Legrand, Fatema A.; Verardi, Paulo H.; Jones, Leslie A.; Chan, Kenneth S.; Peng, Yue; Yilma, Tilahun

doi:10.1128/jvi.78.6.2770-2779.2004

Cited by 60 publications

(70 citation statements)

References 54 publications

(49 reference statements)

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“…Mutants with deletions in these genes show no difference in viral replication in tissue culture (Kettle et al, 1995). Although no significant difference in virulence was seen compared to wild-type virus in murine intranasal model, subsequent study showed that virulence was reduced in both athymic and immunocompetent mice (Legrand et al, 2004). Furthermore, immunogenicity was not reduced by evidence of humoral, T-helper, and cytotoxic T-cell immune responses.…”

Section: Viral Genes As Caspase Inhibitorsmentioning

confidence: 74%

Viruses with deletions in antiapoptotic genes as potential oncolytic agents

Liu

Kirn

2005

Oncogene

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Section: Viral Genes As Caspase Inhibitorsmentioning

confidence: 74%

Viruses with deletions in antiapoptotic genes as potential oncolytic agents

Liu

Kirn

2005

Oncogene

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“…3d). As experiments in mice have demonstrated that the forced expression of IFN-c can strongly enhance VACV clearance and promote immune responses (20)(21)(22), this suggested that concomitant induction of IL-10 and/or TGF-b might limit the activity of CD8 T-cell-derived IFN-c, which would antagonize the clearance of the virus from the ovary.…”

Section: Vacv Infection In the Ovaries Induces Immune Cell Infiltratimentioning

confidence: 99%

Preferential Replication of Vaccinia Virus in the Ovaries is Independent of Immune Regulation Through IL-10 and TGF-β

Zhao

Adams²,

Croft³

2011

Viral Immunology

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Vaccinia virus (VACV) exhibits a strong tropism for ovarian tissue and can cause ovary pathology and sterility. Why VACV preferentially accumulates in this organ is not known. Here we show that multiple immune cell populations infiltrated the ovaries following VACV infection, including virus-specific CD8 T cells making both IFN-c and TNF. This was also accompanied by the induction of interleukin (IL)-10 and TGF-b, suggesting that VACV may exploit the ovarian environment for immune evasion via induction of these suppressive cytokines. To test this we used several strategies, including neutralizing these cytokines, and exogenous targeting of the T-cell response, to determine if this inhibited virus replication in the ovaries. We found that the VACV-specific CD8 T-cell immunity and the clearance of virus were not enhanced in the ovaries of infected mice in which IL-10 receptor (IL-10R) was blocked with antagonist antibody. VACV replication was also only moderately affected in the ovaries of infected IL-10 knockout mice. Similarly, blockade of TGF-b with antagonist antibody demonstrated no effect on CD8 T-cell immunity or VACV replication. Lastly, an agonist antibody targeting the tumor necrosis factor receptor superfamily member OX40 (TNFRSF4) enhanced the number of VACV-specific CD8 T cells producing IFN-c in lymphoid tissue, but had no effect on CD8 T-cell infiltration of the ovaries or on the viral load. Collectively, the results indicate that preferential replication of VACV in the ovaries may not be dependent on immune suppressive mechanisms in this tissue.

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“…Intraperitoneal inoculation of immunodeficient mice is an established model for studying disseminated VV infection (14,15,(17)(18)(19). We demonstrated that nude mice inoculated with vNef157 survived significantly longer than those inoculated with vNef1A11 and v50 (Fig.…”

Section: Discussionmentioning

confidence: 98%

“…The expression of Nef157 may have retarded viral replication by reducing virus spread, ultimately resulting in increased time of survival. Furthermore, the murine intranasal model of VV infection has previously been reported to be a sensitive route for the study of pathogenesis and virulence (14,15,20). Immunocompetent CB6F 1 mice inoculated with v50 and vNef1A11 displayed significant weight loss compared with mice inoculated with vNef157, although mice infected with vNef1A11 recovered from weight loss faster than those infected with v50 (Fig.…”

Section: Discussionmentioning

confidence: 99%

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Nef from pathogenic simian immunodeficiency virus is a negative factor for vaccinia virus

Chan

Verardi

Legrand

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

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The nef gene of human and simian immunodeficiency viruses (HIV and SIV) is important for pathogenicity and maintenance of high virus loads. We previously reported that recombinant vaccinia viruses (rVVs) expressing nef from attenuated SIVmac1A11 (vNef1A11) produced typical plaques on thymidine kinase-deficient 143B cells, whereas rVVs expressing nef derived from the pathogenic SIVmac239 (vNef157) formed plaques with altered morphology. Here, we show that vNef157 is attenuated in normal and nude mice, whereas the pathogenicity of vNef1A11 is similar to that of a control virus. Thus, Nef157 is an attenuating factor in the vaccinia virus (VV) system, contrasting sharply with its function in lentiviruses. We also show that Nef157 inhibits VV cell-to-cell spread, causing formation of atypical plaques regardless of thymidine kinase deficiency, neoplasticity, and species of the infected cell line. We hypothesized that Nef157 interferes with VV spread by association with actin, but no direct colocalization of Nef and the cytoskeletal actin network was detected. Instead, higher levels of Nef157 protein were observed, although mRNAs for both nef genes were produced at comparable levels. Thus, the mechanism behind such Nef157 protein accumulation and Nef157-mediated VV attenuation could be related to the process that causes an opposite effect in its native SIV system, making SIVmac239 more pathogenic than SIVmac1A11.attenuation ͉ atypical plaque formation ͉ lentiviruses ͉ poxviruses ͉ virulence

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Induction of Potent Humoral and Cell-Mediated Immune Responses by Attenuated Vaccinia Virus Vectors with Deleted Serpin Genes

Cited by 60 publications

References 54 publications

Viruses with deletions in antiapoptotic genes as potential oncolytic agents

Viruses with deletions in antiapoptotic genes as potential oncolytic agents

Preferential Replication of Vaccinia Virus in the Ovaries is Independent of Immune Regulation Through IL-10 and TGF-β

Nef from pathogenic simian immunodeficiency virus is a negative factor for vaccinia virus

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