B Lymphocytes, but Not Dendritic Cells, Efficiently HIV-1 Trans Infect Naive CD4(+) T Cells: Implications for the Viral Reservoir

Insight into the establishment and maintenance of HIV-1 infection in resting CD4(+) T cell subsets is critical for the development of therapeutics targeting the HIV-1 reservoir. Although the frequency of HIV-1 infection, as quantified by the frequency of HIV-1 DNA, is lower in CD4(+) naive T cells (T(N)) than in the memory T cell subsets, recent studies have shown that T(N) harbor a large pool of replication-competent virus. Interestingly, however, T(N) are highly resistant to direct (cis) HIV-1 infection in vitro, in particular to R5-tropic HIV-1, as T(N) do not express CCR5. In this study, we investigated whether T(N) could be efficiently HIV-1 trans infected by professional antigen-presenting B lymphocytes and myeloid dendritic cells (DC) in the absence of global T cell activation. We found that B cells, but not DC, have a unique ability to efficiently trans infect T(N) in vitro. In contrast, both B cells and DC mediated HIV-1 trans infection of memory and activated CD4(+) T cells. Moreover, we found that T(N) isolated from HIV-1-infected nonprogressors (NP) harbor significantly disproportionately lower levels of HIV-1 DNA than T(N) isolated from progressors. This is consistent with our previous finding that antigen-presenting cells (APC) derived from NP do not efficiently trans infect CD4(+) T cells due to alterations in APC cholesterol metabolism and cell membrane lipid raft organization. These findings support that B cell-mediated trans infection of T(N) with HIV-1 has a more profound role than previously considered in establishing the viral reservoir and control of HIV-1 disease progression.