No abstract

The 5′-leader of the HIV-1 genome contains conserved elements that direct selective packaging of the unspliced, dimeric viral RNA into assembling particles. Using a 2H-edited NMR approach, we determined the structure of a 155-nucleotide region of the leader that is independently capable of directing packaging (Core Encapsidation Signal; ΨCES). The RNA adopts an unexpected tandem three-way junction structure, in which residues of the major splice donor and translation initiation sites are sequestered by long-range base pairing, and guanosines essential for both packaging and high-affinity binding to the cognate Gag protein are exposed in helical junctions. The structure reveals how translation is attenuated, Gag binding promoted, and unspliced dimeric genomes selected, by the RNA conformer that directs packaging.

Although parasite-host co-speciation is a long-held hypothesis, convincing evidence for long-term co-speciation remains elusive, largely because of small numbers of hosts and parasites studied and uncertainty over rates of evolutionary change. Co-speciation is especially rare in RNA viruses, in which cross-species transfer is the dominant mode of evolution. Simian foamy viruses (SFVs) are ubiquitous, non-pathogenic retroviruses that infect all primates. Here we test the co-speciation hypothesis in SFVs and their primate hosts by comparing the phylogenies of SFV polymerase and mitochondrial cytochrome oxidase subunit II from African and Asian monkeys and apes. The phylogenetic trees were remarkably congruent in both branching order and divergence times, strongly supporting co-speciation. Molecular clock calibrations revealed an extremely low rate of SFV evolution, 1.7 x 10(-8) substitutions per site per year, making it the slowest-evolving RNA virus documented so far. These results indicate that SFVs might have co-speciated with Old World primates for at least 30 million years, making them the oldest known vertebrate RNA viruses.

In this study we date the introduction of HIV-2 into the human population and estimate the epidemic history of HIV-2 subtype A in Guinea-Bissau, the putative geographic origin of HIV-2. The evolutionary history of the simian immunodeficiency virus sooty mangabey͞HIV-2 lineage was reconstructed by using available database sequences with known sampling dates, and a timescale for this history was calculated by using maximum likelihood methods. The date of the most recent common ancestor of HIV-2 subtype A strains was estimated to be 1940 ؎ 16 and that of B strains was estimated to be 1945 ؎ 14. In addition we used coalescent theory to estimate the past population dynamics of HIV-2 subtype A in a rural population of Guinea-Bissau. Parametric and nonparametric estimates of the effective number of infections through time were obtained for an equal sample of gag, pol, and env sequences. Our estimates of the epidemic history of HIV-2 subtype A in Guinea-Bissau show a transition from constant size to rapid exponential growth around 1955-1970. Our analysis provides evidence for a zoonotic transfer of HIV-2 during the first half of the 20th century and an epidemic initiation in Guinea-Bissau that coincides with the independence war (1963)(1964)(1965)(1966)(1967)(1968)(1969)(1970)(1971)(1972)(1973)(1974), suggesting that war-related changes in sociocultural patterns had a major impact on the HIV-2 epidemic.T he AIDS epidemic is clearly recognized as a viral zoonosis (1-3). Phylogenetic analysis indicates that multiple interspecies transmissions from simian species have introduced two genetically distinct types of HIV into the human population: HIV-1, closely related to simian immunodeficiency virus (SIV) from chimpanzees (SIV CPZ ), and HIV-2, closely related to SIV from sooty mangabeys (SIV SM ). Whereas HIV-1 group M subtypes (A-D, F, H, J, and K) are spread globally, HIV-2 subtypes are mainly restricted to West Africa and can be categorized as epidemic subtypes (A and B) and nonepidemic subtypes (C-G) (4-7). Biological reasons have been invoked to explain the difference in global epidemiology between HIV-1 and HIV-2, such as lower HIV-2 viral loads that correlate with a lower transmissibility (8-10). However, attempts to compare the history of the epidemics at their respective geographic origins are still lacking.A useful strategy for investigating the epidemic history of HIV combines molecular clock analysis, to estimate the timescale of the epidemic, and coalescent theory, to infer the demographic history of the virus (11). Various molecular clock calculations have dated the most recent common ancestor (MRCA) of HIV-1 group M around 1930 Ϯ 15 (12-14). HIV-1 group M has subsequently spread globally, generating the pandemic observed today. Here, we investigate the epidemic history of HIV-2 to test previously suggested hypotheses of its origin. We provide the first estimated dates of cross-species transmissions of HIV-2. Our results indicate a transfer of HIV-2 subtypes A and B from sooty mangabeys to humans during the fi...