Species-Specific Activity of HIV-1 Vpu and Positive Selection of Tetherin Transmembrane Domain Variants

Tetherin/BST-2/CD317 is a recently identified antiviral protein that blocks the release of nascent retrovirus, and other virus, particles from infected cells. An HIV-1 accessory protein, Vpu, acts as an antagonist of tetherin. Here, we show that positive selection is evident in primate tetherin sequences and that HIV-1 Vpu appears to have specifically adapted to antagonize variants of tetherin found in humans and chimpanzees. Tetherin variants found in rhesus macaques (rh), African green monkeys (agm) and mice were able to inhibit HIV-1 particle release, but were resistant to antagonism by HIV-1 Vpu. Notably, reciprocal exchange of transmembrane domains between human and monkey tetherins conferred sensitivity and resistance to Vpu, identifying this protein domain as a critical determinant of Vpu function. Indeed, differences between hu-tetherin and rh-tetherin at several positions in the transmembrane domain affected sensitivity to antagonism by Vpu. Two alterations in the hu-tetherin transmembrane domain, that correspond to differences found in rh- and agm-tetherin proteins, were sufficient to render hu-tetherin completely resistant to HIV-1 Vpu. Interestingly, transmembrane and cytoplasmic domain sequences in primate tetherins exhibit variation at numerous codons that is likely the result of positive selection, and some of these changes coincide with determinants of HIV-1 Vpu sensitivity. Overall, these data indicate that tetherin could impose a barrier to viral zoonosis as a consequence of positive selection that has been driven by ancient viral antagonists, and that the HIV-1 Vpu protein has specialized to target the transmembrane domains found in human/chimpanzee tetherin proteins

Occult Hepatitis B Virus Infection: An Old Entity With Novel Clinical Involvements

Background. Occult hepatitis B infection (OBI) is recognized as a risk factor for cirrhosis and hepato-cellular carcinoma. However, OBI brings together a large spectrum of patients who might harbor different characteristics and prognosis.Methods. We analyzed the databases of a university hospital in Paris to identify OBI among patients (n = 3966) concomitantly tested for hepatitis B virus (HBV) DNA and serology during a 7-year period. OBI patients were gathered into clinical entities according to their clinical records.Results. Forty-seven OBIs were identified (1.2%). All patients had detectable anti-HBc, isolated (n = 26) or associated with anti-HBs (n = 21). The proportion of OBIs was 3.4% for patients with isolated anti-HBc and 4.2% for patients with both anti-HBc and anti-HBs. Four clinical categories of OBI patients were identified: patients with a passed HBV infection with HBs Ag clearance (group A, 23.4%); HBV-exposed patients receiving immunosuppressive therapy (group B, 29.8%); HIV/HBV-coinfected patients with therapy discontinuation (group C, 17%); HBV-exposed patients with severe liver conditions (group D, 29.8%). Significant follow-up was available for 32 patients, showing a more deleterious prognosis in group D patients, associated more with their underlying condition than the OBI status.Conclusions. OBI is a heterogeneous condition with various clinical implications

Intérêt de la Numération des Lymphocytes T CD4+ chez les Patients Infectés par le VIH et suivis dans le district sanitaire de Ségou (Mali).

But du travail : Le but de notre étude était de suivre l’évolution du taux de lymphocytes T CD4+ chez les patients infectés par le VIH à Ségou (Mali). Matériel et Méthodes : Nous avons recruté 270 patients infectés par le VIH. La numération des lymphocytes T CD4+ a été faite à l’aide d’un cytomètre de flux FACSCount. La numération des lymphocytes T CD4+ a été effectuée au début puis aux 6ème, 12ème et 18ème mois du traitement antirétroviral. Résultats : Sur 270 patients, 193 (71,4 %) sont âgés de 25 à 44 ans, 190 (70 %) sont du sexe féminin. Le VIH-1 prédomine à Ségou. Aux 6ème, 12ème et 18ème mois du traitement antirétroviral le taux des lymphocytes T CD4+ était compris entre 200 et 350 chez 54,3 %, 74,5 % et 77,4 % de nos patients respectivement. Au 18ième mois, il y avait une différence significative entre les moyennes du taux des lymphocytes T CD4+ chez les patients dont le taux est compris entre 200 - 350 à M0 et M18 (p < 0,01). Conclusion : Le traitement antirétroviral a amélioré l’état immunitaire chez nos patients avec une augmentation considérable du taux des lymphocytes T CD4+. Nous recommandons l’utilisation du FASCount dans le suivi en zone décentralisée pour les patients infectés par le VIH