Browsing by Author "Langevin, S."

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The complexity of circulating HIV type 1strains in Oyo state, Nigeria
(Mary Ann Liebert, Inc, 2007) Sankale, J.; Langevin, S.; Odaibo, G. T.; Meloni, S. T.; Ojesina, A. I.; Olaleye, D.; Kanki, P.
Multiple HIV-1 subtypes and circulating recombinant forms (CRFs) are known to circulate in west Africa. We undertook a survey of HIVs in Oyo state, in southwestern Nigeria. We analysed 71 samples from Ibadan the capital city, and 33 samples form Saki, 100 miles west of Ibadan. We sequenced part of the gag gene and the envelope C2V3 region from 102 and 89 samples, respectively. In the 87 samples for which both genes were sequenced, subtypes G and CRF02_AG were found in equal proportions (32.2%each). Other samples included CRF06_cpx(8.0%), subtype A (2.3%), C(1.1%), unclassified(1.1%), or discordant sequences suggesting the presence of a large number of recombinants involving CRF02_AG and/or subtype G(20.7%) or other subtypes(2.3%). The subtype/CRF designation was concordant in two gene fragments in the majority of samples evaluated. However, we observed difference in subtype distribution between the two locations with a predominance of subtypes G in Ibadan and CRF02 in Saki. This is first in-depth analysis of HIV variability at a state level in Nigeria. Our analysis revealed a significant level of viral heterogeneity and a geographical difference in subtype distribution, and demostrated that CRF02_AG does not account for the majority of circulating strains.
Subtypes-specific patterns in HIV type 1reverse transcriptase and protease in Oyo state, Nigeria: implications for drug resistance and Host Response
(Mary Ann Liebert, Inc, 2006) Ojesina, A. I.; Sankale, J.; Odaibo, G.; Langevin, S.; Meloni, S. T.; Sarr, A. D.; Olaleye, D.; Kanki, P. J.
As the use of antiretroviral therapy becomes more widespread across Africa, it is imperative to characterize baseline molecular variability and subtype-specific peculiarities of drug targets in non-subtype B HIV-1 infection. We sequenced and analyzed 35 reverse transcriptase (RT) and 43 protease (PR) sequences from 50 therapy-naive HIV-1-infected Nigerians. Phylogenetic analyses of RT revealed that the predominant viruses were CRF02_AG (57%), subtype G (26%), and CRF06_cpx (11%). Six of 35 (17%) individuals harbored primary mutations for RT inhibitors, including M41L, V118I, Y188H, P236L, and Y318F, and curiously three of the six were infected with CRF06_cpx. Therefore, CRF06_cpx drug-naive individuals had significantly more drug resistance mutations than the other subtypes (p = 0.011). By combining data on quasisynonymous codon bias with the influence of the differential genetic cost of mutations, we were able to predict some mutations, which are likely to predominate by subtype, under drug pressure. Some subtype-specific polymorphisms occurred within epitopes for HLA B7 and B35 in the RT, and HLA A2 and A*6802 in PR, at positions implicated in immune evasion. Balanced polymorphism was also observed at predicted serine-threonine phosphorylation sites in the RT of subtype G viruses. The subtype-specific codon usage and polymorphisms observed suggest the involvement of differential pathways for drug resistance and host-driven viral evolution in HIV-1 CRF02_AG, subtype G, and CRF06_cpx, compared to subtype B. Subtype-specific responses to HIV therapy may have significant consequences for efforts to provide effective therapy to the populations infected with these HIV-1 subtypes