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Pathogenic Correlates of the Simian Immunodeficiency Virus (SIV)-Associated B Cell Dysfunction.

Pathogenic Correlates of the Simian Immunodeficiency Virus (SIV)-Associated B Cell Dysfunction.
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Brocca-Cofano E, Kuhrt D, Siewe B, Xu C, Haret-Richter GS, Craigo J, Labranche C, Montefiori DC, Landay A, Apetrei C, Pandrea I,


Brocca-Cofano E, Kuhrt D, Siewe B, Xu C, Haret-Richter GS, Craigo J, Labranche C, Montefiori DC, Landay A, Apetrei C, Pandrea I, (click to view)

Brocca-Cofano E, Kuhrt D, Siewe B, Xu C, Haret-Richter GS, Craigo J, Labranche C, Montefiori DC, Landay A, Apetrei C, Pandrea I,

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Journal of virology 2017 09 20() pii 10.1128/JVI.01051-17

Abstract

We compared and contrasted pathogenic (pigtailed macaques-PTMs) and nonpathogenic (African green monkeys-AGMs) SIVsab infections to assess the significance of the B-cell dysfunction observed in SIV/HIV infection. We report that the loss of B cells is specifically associated with the pathogenic SIV infection, while in the nonpathogenic natural hosts B cells rapidly increase in both LNs and intestine. SIV-associated B-cell dysfunction associated to the pathogenic SIV infection is characterized by loss of naïve B cells; loss of resting memory B cells due to their redistribution to the gut; increases of the activated B cells and circulating tissue-like memory B cells and expansion of the B regulatory cells. While circulating B cells are virtually restored to preinfection levels during the chronic pathogenic SIV infection, restoration is mainly due to an expansion of the "exhausted", virus-specific B cells, i.e., activated memory cells and tissue-like memory B cells. Despite of the B-cell dysfunction, SIV-specific Ab production was higher in the PTMs than in AGMs, with the caveat that rapid disease progression in PTMs was strongly associated with lack of anti-SIV Ab. Neutralization titers, the avidity and maturation of immune responses did not differ between pathogenic and nonpathogenic infections, with the exception of the conformational epitope recognition, which evolved from low to high conformations in the nonpathogenic host. The patterns of humoral immune responses in the natural host are therefore more similar to those observed in HIV-infected subjects, suggesting that natural hosts may be more appropriate for modeling the immunization strategies aimed at preventing HIV disease progression. The numerous differences between the pathogenic and nonpathogenic infections with regard to dynamics of the memory B-cell subsets point to their role in the pathogenesis of HIV/SIV infections, and suggest that monitoring B cells may be a reliable approach for assessing disease progression.IMPORTANCE We report here that the HIV/SIV-associated B cell dysfunction (defined by loss of total and memory B cells, increased Breg counts and B cell activation and apoptosis) is specifically associated to pathogenic SIV infection and absent during the course of nonpathogenic SIV infection in natural NHP hosts. Alterations of the B cell population are not correlated with production of neutralizing antibodies, which is similar in both species. Rapid progressive infections associate a severe impairment in SIV-specific antibody production. While we did not find major differences in avidity and maturation between the pathogenic and nonpathogenic SIV infection, we identified a major difference in conformational epitope recognition, with the nonpathogenic infection being characterized by an evolution from low to high conformations. B cell dysfunction should be considered in designing immunization strategies aimed at preventing HIV disease progression.

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