アクティブボード・２０１１年　９月
　　　　　・・・・・２０１１年　９月　１日更新・・・・・

研究発表を行った学会；
・Keystone Symposia HIV Evolution, Genomics and Pathogenesis (X7)
　２０１１年　３月２０日〜２５日（Whistler, Canada）

タイトル；Impairment of the virion infectivity by nef alleles from HIV elite controllers.

発表者；Philip Mwimanzi　氏
　　　（熊本大学　エイズ学研究センター　上野プロジェクト研究室）
Abstract；
Factors contributing to durable control of HIV-1 in elite controllers (EC) are not yet fully described. It is becoming evident that structural and enzymatic proteins (gag, pol, and env) of HIV-1 isolated from EC exhibit impaired function in vitro. However, it remains elusive whether similar deficits exist for accessory genes from EC such as Nef, a viral factor that augments HIV-1 pathogenesis in vivo. Because Nef-mediated enhancement of viral infectivity is thought to be an important factor in boosting HIV-1 replication, we asked in the present study whether nef alleles isolated from EC exhibit functional impairments compared to those isolated from chronic progressors (CP). To address this question, we prepared a panel of recombinant NL4-3 viruses encoding plasma HIV RNA-derived nef alleles from 48 EC and 48 CP and measured their infectivity using a single round replication assay. All recombinant viruses showed at least 10-fold greater infectivity compared to nef-deleted NL4-3. Recombinant viruses expressing patient-derived nef exhibited a wide range of infectivity values, with some exhibiting up to 3-fold greater and others exhibiting up to 4-fold lesser infectivity compared to control NL4-3 viruses containing the nef allele derived from reference strain SF2. Overall, virion infectivity varied across a >15-fold range among all viruses examined, confirming that nef alleles play a substantial role in enhancement of virion infectivity. Comparison of virion infectivity between nef alleles from EC and CP revealed a 3-fold lesser infectivity among EC-derived viruses compared to those from CP (p<0.001). This result remained statistically significant after removal of N=26 HLA-B*57+ subjects from the analysis (p<0.001). Furthermore, we observed no significant difference in virion infectivity between subjects positive and negative for HLA-B*57 in either the EC or CP, suggesting that HLA B*57-associated immune pressures do not play a prominent role in the impairment of nef’s ability to enhance virion infectivity. However, results do support a potentially important role for impaired Nef activity in enhancement of viral infectivity, which could contribute at least in part to the spontaneous viral control observed in elite controllers.