Chemokine coreceptor usage and HIV-1 subtype C reservoir in AIDS patients

Abstract

HIV pathogenesis relies on infection of CD4+ cells. Viral entry into these cells initially utilizes CCR5 to infect monocytes and macrophages, and may later use CXCR4 to infect T cells. Later stage HIV infection progressing towards AIDS is characterized by high viral load and CD4+ T cell depletion. In HIV-1 subtype C infections, there is rarely a switch to CXCR4. However, T cells, which are predomoninantly CXCR4+ cells, still decrease in number. To shed some light on the cause of T cell depletion, HIV-gag specific FISH and HIV V3 loop sequencing were used to assert the location of the virus, and the chemokine coreceptor used, respectively. The majority of CD4+ cells in blood and bone marrow extracts of late stage HIV+ patients possessed positive signals. T cells were present in large number compared to monocytes/ macrophages in both compartments. Sequencing indicated CCR5 was still the preferred chemokine coreceptor. These findings support the hypothesis that the virus is able to enter T cells, despite a lack of coreceptor switching. It also raises the questions of whether CCR5 is upregulated on T cells, or other mechanisms are used by the virus to gain entry into T cells.