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研究発表を行った学会；
・2nd Kumamoto IRCMS International Symposium and 17th Kumamoto AIDS Seminar
　　2016年10月31日〜11月 2日（熊本）

タイトル；Naturally occurring HIV-1 Nef variants that impair Nef’s ability to counteract SERINC5 and enhance virion infectivity.
発表者；豊田　真子　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）
要旨；
Nef is a multi-functional protein that is involved in downregulation of viral entry receptors (CD4, CCR5, and CXCR4) and MHC class I, enhancement of virion infectivity, and stimulation of viral replication. Recently, the host cell proteins serine incorporator (SERINC) 3 and 5 have been revealed as inhibitors of HIV-1 virion infectivity that are counteracted by Nef. It is reported that the alanine mutation at the highly conserved Nef Asp-123 (D123A) impaired the Nef’s ability to counteract SERINC5. However, it remains unclear whether, and if so what extent, naturally occurring patient-derived Nef variants affect Nef’s ability to counteract SERINC5 and enhance virion infectivity. In our separate study, we found that the number of naturally occurring polymorphisms at Y120F and Q125H, located nearby D123, is inversely correlated with plasma viral load in treatment-naïve patients in vivo. In this study, we sought to reveal effects of the two naturally occurring variants on various Nef activities including SERINC5 counteraction and enhancement of virion infectivity. The introduction of both Y120F/Q125H mutations to a control strain NefSF2 impaired the ability to enhance virion infectivity using a single round infectivity assay with TZM-bl cells. Ectopic expression of SERINC5 in the virus producing 293T cells further reduced the virion infectivity. In contrast, no substantial difference was observed in Nef’s ability to downregulate CD4 and MHC class I, suggesting that genetically separable Nef residues are responsible for SERINC5 counteraction. Taken together, our results indicate that Nef’s ability to counteract SERINC5 and enhance virion infectivity is selectively impaired by the naturally occurring Nef Y120F/Q125H mutations that are associated with reduced plasma viremia in infected host.