tailieunhanh - Báo cáo y học: "The evolution of HIV-1 reverse transcriptase in route to acquisition of Q151M multi-drug resistance is complex and involves mutations in multiple domains"

Tuyển tập các báo cáo nghiên cứu về y học được đăng trên tạp chí y học Respiratory Research cung cấp cho các bạn kiến thức về ngành y đề tài: The evolution of HIV-1 reverse transcriptase in route to acquisition of Q151M multi-drug resistance is complex and involves mutations in multiple domains. | Mbisa et al. Retrovirology 2011 8 31 http content 8 1 31 RETR0VIR0L0GY RESEARCH Open Access The evolution of HIV-1 reverse transcriptase in route to acquisition of Q151M multi-drug resistance is complex and involves mutations in multiple domains 1 2 3 3 3 3 Jean L Mbisa Ravi K Gupta Desire Kabamba Veronica Mulenga Moxmalama Kalumbi Chifumbe Chintu f hric l i Dorrx 1 nùorìo K l fCinH4 A A Tỉllzor4 A unQ1 fiiH Doonim DíIItỉx 1 2 CIIIIS M Parry Diana M Gibb Saiaii A walker Patricia A Cane and Deenan Pillay Abstract Background The Q151M multi-drug resistance MDR pathway in HIV-1 reverse transcriptase RT confers reduced susceptibility to all nucleoside reverse transcriptase inhibitors NRTIs excluding tenofovir TDF . This pathway emerges after long term failure of therapy and is increasingly observed in the resource poor world where antiretroviral therapy is rarely accompanied by intensive virological monitoring. In this study we examined the genotypic phenotypic and fitness correlates associated with the development of Q151M MDR in the absence of viral load monitoring. Results Single-genome sequencing SGS of full-length RT was carried out on sequential samples from an HIV-infected individual enrolled in ART rollout. The emergence ofQ151M MDR occurred in the order A62V V75I and finally Q151M on the same genome at 4 17 and 37 months after initiation of therapy respectively. This was accompanied by a parallel cumulative acquisition of mutations at 20 other codon positions seven of which were located in the connection subdomain. We established that fourteen of these mutations are also observed in Q151M-containing sequences submitted to the Stanford University HIV database. Phenotypic drug susceptibility testing demonstrated that the Q151M-containing RT had reduced susceptibility to all NRTIs except for TDF. RT domain-swapping of patient and wild-type RTs showed that patient-derived connection subdomains were not associated with reduced NRTI .