Serum levels of MIP-1beta and RANTES in HIV-1 subtype CRF01_AE infected patients with different rates of disease progression.

The beta-chemokines have been shown to inhibit HIV replication in vitro. To evaluate the role of serum beta-chemokines in disease progression and their anti-viral role in vivo, we determined serum levels of macrophage inflammatory protein-1beta (MIP-1beta) and regulated upon activation normal T-cell expressed and secreted (RANTES) of twenty HIV-1 subtype CRF01_AE infected patients: nine progressors (PRs, follow-up CD4+ cell count < 200/mm3 and progression to AIDS or death) and eleven slower progressors (SPs, asymptomatic and/or follow-up CD4+ cell counts > 350/mm3 at the end of follow-up) and determined their plasma viral loads. The subjects were followed for at least 36 months. All had initial CD4 values > 350 cells/mm3. In this longitudinal study, serum levels of MIP-1beta and RANTES in specimens obtained either early or later in the course of HIV infection did not differ significantly between progressors and slower progressors (p > 0.05). There were no significant changes in serum MIP-1beta and RANTES levels over time in either patient group (p > 0.05). No significant associations were observed between plasma viral loads and the measured beta-chemokines (r = -0.205, p = 0.21 for MIP-1beta and r = -0.12, p = 0.492 for RANTES). The results suggest these chemokines do not play a major systemic role in control of viremia or protection against the progression of HIV disease.

In vitro susceptibility of Thai seronegative donor CD8+ T lymphocytes to human immunodeficiency virus-1 (HIV-1) infection.

To determine whether CD8+ T lymphocytes from Thai donor cells are susceptible to HIV-1 infection, undepleted peripheral blood mononuclear cells (PBMC) and CD8-enriched PBMC were infected with HIV-1 Thai subtype B and CRF01_AE (E) primary isolates. Virus kinetics in HIV-1 infection of CD4+ and CD8+ T lymphocytes peaked at day 7 or 10 post infection (pi); the TCID50 used for cell infection was proportional to the level of p24 production in the cultures. We also found that the level of p24 antigen in the supernatants of infected undepleted PBMC was significantly higher than that of infected CD8-enriched PBMC. Interestingly, both single positive T lymphocytes (CD4+ and CD8+ T lymphocytes) as well as double positive CD4+/CD8+ T lymphocytes were infected with HIV-1. The double positive T lymphocytes in PBMC were found only in the presence of both CD4+ and CD8+ T lymphocytes. The majority of p24+/CD4-/CD8- T lymphocytes were HIV-1 infected CD4 down-modulated PBMC. This report provides direct evidence that single positive CD8+ T lymphocytes and double positive CD4+/ CD8+ T lymphocytes from Thai donors can be infected with HIV-1 subtypes B and E in vitro.