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Background  HIV-1 subtype C (HIV-1C) accounts for almost 50% of all HIV-1 infections worldwide and predominates in countries with the highest case-loads globally. Functional studies suggest that HIV-1C is unique in its biological properties, and there are contradicting reports about its replicative characteristics. The present study was conducted to evaluate whether the host cytokine environment modulates the  in vitro  replication capacity of HIV-1C viruses.    Methods  A small subset of HIV-1C isolates showing efficient replication in peripheral blood mononuclear cells (PBMC) is described, and the association of  in vitro  replication capacity with disease progression markers and the host cytokine response was evaluated. Viruses were isolated from patient samples, and the corresponding  in vitro  growth kinetics were determined by monitoring for p24 production. Genotype, phenotype and co-receptor usage were determined for all isolates, while clinical category, CD4 cell counts and viral loads were recorded for all patients. Plasmatic concentrations of cytokines and, acute-phase response, and microbial translocation markers were determined; and the effect of cytokine treatment on  in vitro  replication rates was also measured.    Results  We identified a small number of viral isolates showing high  in vitro  replication capacity in healthy-donor PBMC. HIV-1C usage of CXCR4 co-receptor was rare; therefore, it did not account for the differences in replication potential observed. There was also no correlation between the  in vitro  replication capacity of HIV-1C isolates and patients' disease status. Efficient virus growth was significantly associated with low interleukin-10 (IL-10), interleukin-22 (IL-22), and C-reactive protein (CRP) levels in plasma (p < .0001).  In vitro , pretreatment of virus cultures with IL-10 and CRP resulted in a significant reduction of virus production, whereas IL-22, which lacks action on immune cells appears to mediate its anti-HIV effect through interaction with both IL-10 and CRP, and its own protective effect on mucosal membranes.    Conclusions  These results indicate that high systemic levels of IL-10, CRP and IL-22 in HIV-1C-infected Indian patients are associated with low viral replication  in vitro , and that the former two have direct inhibitory effects whereas the latter acts through downstream mechanisms that remain uncertain.

retrovirology

High systemic levels of interleukin-10, interleukin-22 and C-reactive protein in Indian patients are associated with low in vitroreplication of HIV-1 subtype C viruses