T cell independent secondary antibody responses to the envelope protein of simian immunodeficiency virus

Retrovirology

Klaus Überla²  Matthias Tenbusch²  Seraphin Kuate¹  Claudius Großmann²  Vladimir Temchura²  Ghulam Nabi² 

[1] Immune Biology of Retroviral infections, VB, CCR, NCI, NIH, Bethesda, USA;Department of Molecular and Medical Virology, Ruhr University Bochum, D-44780, Bochum, Germany

关键词: VLP;    T-independent antibody response;    Adenoviral vectors;    HIV;    SIV;   

Others  :  1209301
DOI  :  10.1186/1742-4690-9-42

 received in 2012-01-17, accepted in 2012-05-14,  发布年份 2012

【 摘 要 】

Background

During human (HIV) and simian (SIV) immunodeficiency virus infection, loss of CD4+ T cells and progression to AIDS are associated with a decline in antibody titers to the viral Gag protein, while antibodies to the Env protein remain high, suggesting a T cell independent antibody response to Env.

Results

To explore differential regulation of Gag and Env antibody responses, immunocompetent BALB/c and T cell deficient nude mice were immunized with virus like particles (VLP) of simian immunodeficiency virus or adenoviral vectors expressing SIV Gag and Env. High levels of antibodies against Gag and Env could only be induced in immunocompetent mice, but not in the immunodeficient mice. Thus, neither cells expressing Env after adenoviral gene transfer nor VLPs induce a T cell independent primary anti-Env antibody response. However, secondary B cell responses to Env, but not to Gag, were observed in immunodeficient mice after transfer of primed B cells and boosting with VLPs or adenoviral vectors expressing Gag and Env. This T cell independent secondary antibody response to Env was reduced after stimulation with VLPs modified to contain monomeric membrane bound gp130 surface subunit of Env and undetectable after injection of soluble gp130.

Conclusions

Membrane-bound trimeric Env seems to be responsible for the maintenance of high levels of anti-Env antibodies during progression to AIDS. This T cell independent secondary antibody response may prevent T cell-dependent affinity maturation and thus contribute to viral immune escape by favoring persistence of non-protective antibodies.

【 授权许可】

   
2012 Nabi et al.; licensee BioMed Central Ltd.

【 图 表 】

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