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研究発表を行った学会;Cold Spring Harbor Laboratory Retroviruses meeting
2019年 5月20日〜25日(Hungtington, USA)
タイトル; A single amino acid change in an extracellular loop of SERINC5 attenuates the ability to restrict HIV-1 infectivity.
発表者;Tan Toong Seng氏
(ヒトレトロウイルス学共同研究センター 熊本大学キャンパス 感染免疫学分野)
SERINC5 is a host restriction factor of HIV-1 infectivity that is counteracted by a viral accessory protein Nef. However, mechanism of infectivity restriction by SERINC5 remains elusive. To explore this issue, a 11-mer bioluminescence-tag peptide was introduced to all four intra and five extracellular loops of SERINC5 and infectivity was assessed using the virion particles produced from 293T cells co-transfected with NL43-ΔNef and a series of SERINC5 mutants. We found that a near-complete loss of infectivity restriction function when the tag was introduced in the last loop of SERINC5 (loop 9, amino acid 410 – 429). Introduction of single alanine mutations to SERINC5 loop 9 with an internal HA tag (SERINC5-iHA) revealed that N410A, W411A and F412A impaired infectivity restriction function. In contrast, as revealed by Western blot, the F412A mutant exhibited greater steady-state expression level in 293T cells compared to wild type; whereas expression level of the remaining mutants was much impaired. Furthermore, the F412A mutant expressed at the cell surface and incorporated in the nascent virions to a greater extent than the wild type SERINC5. Moreover, co-transfection of JTAg cells lacking SERINC3/5 expression with the plasmid encoding F412A SERINC5 and NL43-ΔNef demonstrated that the infectivity restriction function was impaired even though the substantial amounts of F412A SERINC5 incorporated in the secreted virion particles, corroborating all the findings made by 293T cells. Taken together, these results suggest that extracellular loop 9 plays, at least partly, important roles in infectivity restriction by SERINC5, warrant for further investigation.

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