An African perspective on mucosal immunity and HIV-1.

HIV prevention mandates an understanding of the mechanisms of mucosal immunity with attention to some unique features of the epidemic and mucosal environment in the developing world. An effective vaccine will have to induce mucosal protection against a highly diverse virus, which is equipped with a number of immune evasion strategies. Its development will require assessment of mucosal immune responses, and it will have to protect a mucosal environment where inflammation and altered immune responses are common because of the presence of other mucosal infections, such as sexually transmitted infections and parasites, and where nutritional status may also be compromised. Ideally, not only prevention methods would protect adults but also provide cover against gastrointestinal transmission through maternal milk. Prevention might also be complemented by microbicides and circumcision, two alternative approaches to mucosal protection. It seems unlikely that a single solution will work in all instances and intervention might have to act at multiple levels and be tailored to local circumstances. We review here some of the mucosal events associated with HIV infection that are most relevant in an African setting.

nef/long terminal repeat quasispecies from HIV type 1-infected Mexican patients with different progression patterns and their pathogenesis in hu-PBL-SCID mice.

To examine the genetic features of the long terminal repeat (LTR) derived from six HIV-1-infected individuals enrolled in the Mexico City Cohort, we cloned and sequenced a 505-bp fragment of the proviral LTR from their peripheral blood mononuclear cells (PBMCs). All patients harbored HIV-1 LTR quasispecies corresponding to the B subtype. Three patients with high CD4+ T cell counts (>500/mm3) presented LTR sequences with point mutations in the TAR bulge. The LTR sequence from a patient classified as a long-term nonprogressor (LTNP) presented the most frequent naturally occurring length polymorphism (MFNLP) and two substitutions in the TAR region that were predicted to result in two alternative secondary RNA structures. A novel 18-bp deletion, which eliminates part of the putative binding site for the nuclear factor of activated T cells (NFAT-1), was identified in the overlapping nef/LTR sequence derived from a patient progressing to AIDS. This deletion coincides with the ability of this virus to consistently replicate at low levels in vivo (viral load <500 RNA copies/ml) and in vitro (unsuccessful virus isolation). On one occasion, when virus isolation was successful, the 18-bp deletion was no longer evident and LTR sequences with intact NFAT-1-binding sites were observed. Inoculation of hu-PBL-SCID mice with viruses from several Mexican patients resulted in differential CD4+ T cell depletion patterns 15 days postinfection, which agree with the in vivo CD4+ T cell count data from each patient.