Spatiotemporal dynamics of simian immunodeficiency virus brain infection in CD8+ lymphocyte-depleted rhesus macaques with neuroAIDS.

Despite the success of combined antiretroviral therapy in controlling viral replication in human immunodeficiency virus (HIV)-infected individuals, HIV-associated neurocognitive disorders, commonly referred to as neuroAIDS, remain a frequent and poorly understood complication. Infection of CD8(+) lymphocyte-depleted rhesus macaques with the SIVmac251 viral swarm is a well-established rapid disease model of neuroAIDS that has provided critical insight into HIV-1-associated neurocognitive disorder onset and progression. However, no studies so far have characterized in depth the relationship between intra-host viral evolution and pathogenesis in this model. Simian immunodeficiency virus (SIV) env gp120 sequences were obtained from six infected animals. Sequences were sampled longitudinally from several lymphoid and non-lymphoid tissues, including individual lobes within the brain at necropsy, for four macaques; two animals were sacrificed at 21 days post-infection (p.i.) to evaluate early viral seeding of the brain. Bayesian phylodynamic and phylogeographic analyses of the sequence data were used to ascertain viral population dynamics and gene flow between peripheral and brain tissues, respectively. A steady increase in viral effective population size, with a peak occurring at ~50-80 days p.i., was observed across all longitudinally monitored macaques. Phylogeographic analysis indicated continual viral seeding of the brain from several peripheral tissues throughout infection, with the last migration event before terminal illness occurring in all macaques from cells within the bone marrow. The results strongly supported the role of infected bone marrow cells in HIV/SIV neuropathogenesis. In addition, our work demonstrated the applicability of Bayesian phylogeography to intra-host studies in order to assess the interplay between viral evolution and pathogenesis.

HIV type 1 genetic variability in central Brazil.

This study analyzed the genes pol and env to determine the genetic variability of HIV-1 in Central Brazil. Forty-one isolates of HIV-1-infected individuals had protease, reverse transcriptase, and C2C3/ env amplified by nested PCR and sequenced. The subtype was determined by the program REGA and phylogenetic analyses. The samples identified as putative recombinant forms were analyzed by SimPlot. A high prevalence of subtype B (95.1%) was observed, followed by mosaic viruses B/F (4.9%). The amino acid sequences from 30 HIV-1 isolates were analyzed for the antigenic intrasubtype diversity. The most prevalent gp120 V3 loop motif was the GPGR (United States/Europe) (43.3%), described in B and F subtypes, followed by the GPGK tetrapeptide (10%). The Brazilian variant B" (GWGR), GFGR, and GLGR tetrapeptides were found in 6.7%. Other V3 variants were found in eight isolates (26.7%). Phylogenetic tree analysis was also performed in order to verify the relationship of the HIV-1 samples from Central Brazil with other HIV-1 sequences that circulate in Brazil. The subtype B sequences from Central Brazil formed a polyphyletic cluster in the tree, indicating that these strains are similar to those from other geographic regions. These results contribute to the understanding of HIV in Brazil, and may prove useful for the development of vaccine candidates.

The spread of HIV in Pakistan: bridging of the epidemic between populations.

In the last two decades, 'concentrated epidemics' of human immunodeficiency virus (HIV) have established in several high risk groups in Pakistan, including Injecting Drug Users (IDUs) and among men who have sex with men (MSM). To explore the transmission patterns of HIV infection in these major high-risk groups of Pakistan, 76 HIV samples were analyzed from MSM, their female spouses and children, along with 26 samples from a previously studied cohort of IDUs. Phylogenetic analysis of HIV gag gene sequences obtained from these samples indicated a substantial degree of intermixing between the IDU and MSM populations, suggesting a bridging of HIV infection from IDUs, via MSM, to the MSM spouses and children. HIV epidemic in Pakistan is now spreading to the female spouses and offspring of bisexual MSM. HIV control and awareness programs must be refocused to include IDUs, MSM, as well as bisexual MSM, and their spouses and children.