Low levels of SIV infection in sooty mangabey central memory CD4+ T cells are associated with limited CCR5 expression

Abstract

Naturally SIV-infected sooty mangabeys (SMs) do not progress to AIDS despite high-level virus replication. We previously showed that the fraction of CD4+CCR5+ T-cells is lower in SMs compared to humans and macaques. Here we found that, after in vitro stimulation, SM CD4+ T-cells fail to up-regulate CCR5, and that this phenomenon is more pronounced in CD4+ central-memory T-cells (TCM). CD4+ T-cell activation was similarly uncoupled from CCR5 expression in SMs in vivo during (i) acute SIV infection and (ii) following antibody-mediated CD4+ T-cell depletion. Remarkably, CD4+ TCM of SMs that express low levels of CCR5 demonstrated reduced susceptibility to SIV infection both in vivo and in vitro when compared to CD4+ TCM of RMs. These data suggest that low CCR5 expression on SM CD4+ T-cells favors the preservation of CD4+ T-cell homeostasis and promotes an AIDS-free status by protecting CD4+ TCM from direct virus infection.

Replicative fitness of transmitted HIV-1 drives acute immune activation, proviral load in memory CD4 + T cells, and disease progression

“…These long-lived memory T cells with stem cell-like properties are susceptible to HIV-1 or SIV in pathogenic infections but are spared in nonpathogenic SIV disease (46). Similarly, the long-lived T CM CD4 + cells are spared in nonpathogenic SIV infection, and infection of this subset has been linked to the immunopathology of HIV-1 infection (30,47). Moreover, recent evidence demonstrates that reduced infection of T SCM and T CM CD4 + cells is associated with a nonprogression phenotype in viremic individuals (48).…”

Microbial Translocation in the Pathogenesis of HIV Infection and AIDS

“…The mechanisms that have been proposed to cause HIV-associated immune activation include (i) the direct effect of specific virus gene products (Env, Nef, and Tat, etc. ), (ii) the innate and adaptive immune responses to the virus, (iii) an ineffective regulation of normally generated antiviral immune responses, (iv) bystander activation of T and B lymphocytes caused by an increased level of production of proinflammatory cytokines (e.g., tumor necrosis factor alpha [TNF-␣], interleukin-1 [IL-1], IL-6, and several others), (v) the presence of clinical or subclinical coinfections, and, more recently, (vi) the preferential infection of central memory CD4 ϩ T cells (as opposed to effector memory CD4 ϩ T cells) as a factor responsible for concentrating the bulk of the antigenic load in central lymphoid tissues (16,17). In this rather complex immunopathogenic context, the translocation of microbial products from the intestinal lumen to the systemic circulation appears to be a central factor that determines the severity of HIV/SIV-associated chronic immune activation.…”

Effect of Combination Antiretroviral Therapy on Chinese Rhesus Macaques of Simian Immunodeficiency Virus Infection

“…[28][29][30] Combination ART can improve restoration of this population of CD4 + T cells in SIV infection as observed in the present study, as well as by others in other systems. 10 In some studies, T CM were defined slightly differently than here, as either CD28 + CCR7 + CCR5 -, 31 CD95 + CD62L + , 23 or CD28 + CD95 + . 32 We used the latter immunophenotyping, which may include the transitional effector memory cells, but this population is in general quite small.…”

“…23,24 To investigate whether there was any reduction of immune activation in the gut during cART, we examined activation of CD4 + and CD8 + T cells throughout cART by comparing their coexpression of HLA-DR. In the jejunum, CD4…”