Effective Downregulation of HLA-A*2 and HLA-B*57 by Primary Human Immunodeficiency Virus Type 1 Isolates Cultured from Elite Suppressors

Abstract

Elite controllers or suppressors (ES) are human immunodeficiency virus type 1 (HIV-1)-infected patients who control viral replication to <50 copies/ml without antiretroviral therapy. Downregulation of HLA class I molecules is an important mechanism used by HIV-1 to evade the immune system. In this study, we showed that primary isolates from ES are as effective as isolates obtained from patients with progressive HIV-1 disease at downregulating HLA-A*2 and HLA-B*57 molecules on primary CD4+ T cells. Thus, a diminished ability of viral isolates from ES to evade HIV-specific immune responses probably does not contribute to the control of viral replication in these patients.

HIV Type 1-Mediated Downregulation of HLA-B*57/B*5801 Proteins on Elite Suppressor CD4+ T Cells

“…3 To determine whether differences in HLA-B*57 downregulation induced by the transmitted virus were responsible for the difference in CTL responses, CD4 þ T cells from both patients were infected with the transmitted replication-competent virus and after staining surface CD4 and HLA-B*57 molecules, the cells were then fixed and permeabilized and stained with the KC57 gag-specific monoclonal antibody (Beckman Coulter) as previously described. 11 The MFI ratio of B57 expression on infected versus uninfected CD4 þ T cells was comparable in the two patients (0.41 for ES, 0.25 for CP) and was similar to the range we have seen in cells from two other ES.…”

“…9,10 We previously have shown that replication-competent viruses isolated from ES and CP were equally efficient at downregulating surface HLA-A*2 and HLA-B*57 proteins on primary CD4 þ T cells. 11 In contrast, it has recently been shown that CD4…”

HIV-1 Nef: a master manipulator of the membrane trafficking machinery mediating immune evasion

“…An additional cohort of 4244 HIV-1 infected individuals in India demonstrated that the frequency of mutations in the PxxP 75 motif of Nef, which is essential for MHC-I downregulation, was greater in patients that progress more slowly, if at all, to AIDS [85]. Interestingly, while other studies have not observed a correlation between rate of progression to AIDS and MHC-I downregulation [86][87][88], these studies were limited by small sample size, with less than a dozen patients per experimental group and likely under-powered to detect significant differences, suggesting further analysis with larger cohorts of HIV-1 infected individuals is warranted.…”

Human immunodeficiency virus type 1 long-term non-progressors: the viral, genetic and immunological basis for disease non-progression

“…Challenging their hypothesis that LTNPs may harbour virus isolates less capable of downregulating HLA class I alleles responsible for generating a robust CTL response, Nou et al (2009) found that isolates from ECs (n55) and progressors (n58) equally downregulated HLA-A2 and HLA-B57 alleles. Furthermore, a recent longitudinal study (O'Connell et al, 2010) that examined proviral and plasma samples from six ECs for 5 years showed that there were no significant mutations in B57/58-and/or B27-restricted gag epitopes.…”