Acute loss of intestinal CD4+ T cells is not predictive of simian immunodeficiency virus virulence.

The predictive value of acute gut-associated lymphoid tissue (GALT) CD4+ T cell depletion in lentiviral infections was assessed by comparing three animal models illustrative of the outcomes of SIV infection: pathogenic infection (SIVsmm infection of rhesus macaques (Rh)), persistent nonprogressive infection (SIVagm infection of African green monkeys (AGM)), and transient, controlled infection (SIVagm infection of Rh). Massive acute depletion of GALT CD4+ T cells was a common feature of acute SIV infection in all three models. The outcome of this mucosal CD4+ T cell depletion, however, differed substantially between the three models: in SIVsmm-infected Rh, the acute GALT CD4+ T cell depletion was persistent and continued with disease progression; in SIVagm, intestinal CD4+ T cells were partially restored during chronic infection in the context of normal levels of apoptosis and immune activation and absence of damage to the mucosal immunologic barrier; in SIVagm-infected Rh, complete control of viral replication resulted in restoration of the mucosal barrier and immune restoration. Therefore, our data support a revised paradigm wherein severe GALT CD4+ T cell depletion during acute pathogenic HIV and SIV infections of humans and Rh is necessary but neither sufficient nor predictive of disease progression, with levels of immune activation, proliferation and apoptosis being key factors involved in determining progression to AIDS.

In vitro characterization of primary SIVsmm isolates belonging to different lineages. In vitro growth on rhesus macaque cells is not predictive for in vivo replication in rhesus macaques.

We report in vitro characterization of 11 SIVsmm strains of six lineages co-circulating in naturally infected sooty mangabeys (SMs) from US Primate Centers and showed no major differences in the in vitro replication pattern between different SIVsmm lineages. Primary SIVsmm isolates utilized CCR5 and Bonzo co-receptors in vitro. SIVsmm growth in human T cell lines was isolate-, not lineage-specific, with poor replication on Molt4-Clone8, CEMss and PM1 cells and better replication on MT2, SupT1 and CEMx174 cells. All primary SIVsmm isolates replicated on SM and human PBMCs. In vitro replication in macaques varied widely, with moderate to high replication in pig-tailed macaque PBMCs, enhanced by CD8+ T cell depletion, and highly variable replication on rhesus macaque (Rh) PBMCs. Primary SIVsmm isolates replicated in Rh monocyte-derived dendritic cells (MDDCs) and monocyte-derived macrophages (MDMs). In vivo, SIVsmm isolates replicated at high levels in all SIVsmm-infected Rh. The poor in vitro replication of primary SIVsmm isolates in Rh cells did not correlate with in vivo replication, emphasizing the value of in vivo studies.

HIV genetic diversity: biological and public health consequences.

The devastating consequences of AIDS pandemic will probably only be controlled when a vaccine is developed that is safe, effective, affordable, and simple enough to permit implementation in developing countries where the impact of AIDS is most severe. However, the major obstacle for the control of the spread of AIDS lies in the diversity of HIV and its enormous evolutionary potential. Numerous HIV forms contribute to the AIDS pandemic. Two viral types (HIV-1 and HIV-2), numerous groups (M, N and O for HIV-1 and A through H for HIV-2) and numerous subtypes, sub-subtypes and circulating recombinant forms (CRF) have emerged during the last 50 years. At least nine different genetic HIV-1 subtypes and over 20 CRFs were defined within group M, which accounts for the majority of cases in the AIDS pandemic. Even though HIV-1 subtype C and A predominate globally, the other viral forms co-circulate all over the world and may have a major impact for the strategies of pandemic control. Here we discuss the distribution of these divergent viral forms worldwide and the potential consequences of such a tremendous viral diversity for diagnostic, monitoring, treatment and the development of an effective vaccine.