11 research outputs found
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Long-Term Intrapatient Evolution During HIV-2 Infection
HIV-2 disease progression and transmission is attenuated compared to HIV-1, yet prospective studies examining HIV-2 intrapatient evolution have been limited. We examined viral sequence evolution in the C2V3C3 region of the viral env gene in 8 HIV-2 infected individuals from Dakar, Senegal, over the course of approximately 10 years. To compare results to HIV-1 infection, we reanalyzed data from our previous study that examined intrapatient evolution in HIV-1 infected individuals from the same population. HIV-2 sequences from early and late timepoints were phylogenetically intermixed for all subjects, and no distinct trends were observed in terms of increases or decreases in fragment size or number of N-linked glycosylation sites. In homologous env C2V3 sequence, rates of viral divergence and diversification were slower in individuals infected with HIV-2 than individuals with HIV-1. This data indicates that viral evolution occurs slowly in HIV-2 infection, which is consistent with the slow disease progression observed in HIV-2 infection, and supports the notion that viral evolution may be a relevant correlate for disease progression
Genomic Sites of Human Immunodeficiency Virus Type 2 (HIV-2) Integration: Similarities to HIV-1 In Vitro and Possible Differences In Vivo
Retroviruses have distinct preferences in integration site selection in the host cell genome during in vitro infection, with human immunodeficiency virus type 1 (HIV-1) integration strongly favoring transcriptional units. Additionally, studies with HIV-1 have shown that the genomic site of proviral integration may impact viral replication, with integration in heterochromatin associated with a block in viral transcription. HIV-2 is less pathogenic than HIV-1 and is believed to have a lower replication rate in vivo. Although differences in integration site selection between HIV-2 and HIV-1 could potentially explain the attenuated pathogenicity of HIV-2, no studies have characterized integration site selection by HIV-2. In this study, we mapped 202 HIV-2 integration sites during in vitro infection of peripheral blood mononuclear cells with a primary HIV-2 isolate. In addition, we assayed for in vivo proviral integration within heterochromatin in 21 HIV-1-infected subjects and 23 HIV-2-infected subjects, using an alphoid repeat PCR assay. During in vitro infection, HIV-2 displayed integration site preferences similar to those previously reported for HIV-1. Notably, 82% of HIV-2 integrations mapped to Refseq genes, and integration strongly favored regions of the genome with high gene density and high GC content. Though rare, the proportion of HIV-2 subjects with evidence of proviral integration within heterochromatin in vivo was higher than that of HIV-1-infected subjects. It is therefore possible that integration site selection may play a role in the differences in HIV-1 and HIV-2 in vivo pathogenesis
The Level of APOBEC3G (hA3G)-Related G-to-A Mutations Does Not Correlate with Viral Load in HIV Type 1-Infected Individuals
The APOBEC family of mammalian cytidine deaminases, such as APOBEC3G (hA3G), has been demonstrated to function as a host viral restriction factor against HIV-1. hA3G has been shown to cause extensive G-to-A mutations in the HIV-1 genome, which may play a role in viral restriction. To investigate the role of G-to-A mutations in HIV-1 pathogenesis, we isolated, amplified, and sequenced HIV-1 sequences (vif, gag, and env) from 29 therapy-naive HIV-1-infected individuals. The levels of G-to-A mutations correlated with the expression levels of hA3G in the vif (rhoâ=â0.438, pâ=â0.041) and the env regions (rhoâ=â0.392, pâ=â0.038), but not in the gag region (rhoâ=â0.131, pâ=â0.582). There is no correlation between viral load and the level of G-to-A mutations in the vif (rhoâ=â0.144, pâ=â0.522), env (rhoâ=â0.168, pâ=â0.391), or gag regions (rhoâ=ââ0.254, pâ=â0.279). Taken together, these findings suggest that the hA3G-induced G-to-A mutations may not be the mechanism by which hA3G restricts or controls viral replication. Thus, hA3G might be restricting viral growth in infected individuals through a mechanism that is independent of the cytidine deaminase activities of hA3G
Direct Evidence of Lower Viral Replication Rates In Vivo in Human Immunodeficiency Virus Type 2 (HIV-2) Infection than in HIV-1 Infectionâż
Studies have shown that human immunodeficiency virus type 2 (HIV-2) is less pathogenic than HIV-1, with a lower rate of disease progression. Similarly, plasma viral loads are lower in HIV-2 infection, suggesting that HIV-2 replication is restricted in vivo in comparison to that of HIV-1. However, to date, in vivo studies characterizing replication intermediates in the viral life cycle of HIV-2 have been limited. In order to test the hypothesis that HIV-2 has a lower replication rate in vivo than HIV-1 does, we quantified total viral DNA, integrated proviral DNA, cell-associated viral mRNA, and plasma viral loads in peripheral blood samples from groups of therapy-naĂŻve HIV-1-infected (n = 21) and HIV-2-infected (n = 18) individuals from Dakar, Senegal, with CD4+ T-cell counts of >200/ÎŒl. Consistent with our previous findings, total viral DNA loads were similar between HIV-1 and HIV-2 and plasma viral loads were higher among HIV-1-infected individuals. Proportions of DNA in the integrated form were also similar between these viruses. In contrast, levels of viral mRNA were lower in HIV-2 infection. Our study indicates that HIV-2 is able to establish a stable, integrated proviral infection in vivo, but that accumulation of viral mRNA is attenuated in HIV-2 infection relative to that in HIV-1 infection. The differences in viral mRNA are consistent with the differences in plasma viral loads between HIV-1 and HIV-2 and suggest that lower plasma viral loads, and possibly the attenuated pathogenesis of HIV-2, can be explained by lower rates of viral replication in vivo
CaractĂ©risation phytochimique et Ă©tude de lâactivitĂ© antimicrobienne dâextraits de feuilles de trois plantes de la flore sĂ©nĂ©galaise : Detarium senegalense, Detarium microcarpum et Piliostigma reticulatum
Detarium senegalense, Detarium microcarpum et Piliostigma reticulatum sont trois plantes de la flore sĂ©nĂ©galaise, utilisĂ©es en mĂ©decine traditionnelle pour la prise en charge de maladies infectieuses. Cette Ă©tude visait Ă dĂ©terminer in vitro lâactivitĂ© antimicrobienne dâextraits et de fractions de feuilles de ces plantes sur diffĂ©rentes souches (Escherichia coli, Klebsiella oxytoca, Pseudomonas aeruginosa, Enterococus faecalis, Staphylococcus aureus et Candida albicans). Les mĂ©thodes de diffusion en milieu solide et de dilution en milieu liquide ont Ă©tĂ© utilisĂ©es pour la dĂ©termination des DiamĂštres dâInhibition (DI) et des Concentrations Minimales Inhibitrices (CMI). Le screening phytochimique a Ă©tĂ© rĂ©alisĂ© par des tests de caractĂ©risation reposant sur des rĂ©actions physico-chimiques et par chromatographie sur couche mince. Sur lâensemble des Ă©chantillons testĂ©s, seule la fraction dichloromĂ©thanique de P. reticulatum Ă©tait inactive sur les souches bactĂ©riennes Ă©tudiĂ©es. Les DI variaient entre 10 et 23 mm pour les Ă©chantillons actifs. Les CMI Ă©taient comprises entre 0,0293 et 2,50 mg/mL. Les fractions dâacĂ©tate dâĂ©thyle Ă©taient les plus actives. Les familles de molĂ©cules suivantes ont Ă©tĂ© identifiĂ©es : tanins, flavonoĂŻdes et saponosides. Les teneurs en polyphĂ©nols totaux variaient de 0,66 Ă 19 mg Ă©quivalent acide tannique/g. Cette Ă©tude a montrĂ© que les extraits des trois plantes sont dotĂ©s dâun fort pouvoir antimicrobien et contiennent plusieurs familles de composĂ©s chimiques