doi:10.1016/j.tim.2017.10.007. chronic stages, the resistance to IFITM3 but not to SERINC5 Endoxifen E-isomer hydrochloride is usually gradually lost. We further discovered a significant correlation between the resistance of HIV-1 Env to soluble CD4 inhibition and the resistance to SERINC5 but not to IFITM3. Interestingly, the miniprotein CD4 mimetic M48U1 sensitizes HIV-1 Env to the inhibition by SERINC5 but not IFITM3. Endoxifen E-isomer hydrochloride Together, these data indicate that SERINC5 and IFITM3 exert differential inhibitory pressures on HIV-1 Env over Rabbit Polyclonal to WEE2 different stages of HIV-1 contamination and that HIV-1 Env uses varied strategies to resist these two restriction factors. IMPORTANCE HIV-1 Env protein is usually exposed to Endoxifen E-isomer hydrochloride the inhibition not only by humoral response, but also by host restriction factors, including serine incorporator 5 (SERINC5) and interferon-inducible transmembrane 3 (IFITM3). This study investigates how HIV-1 envelope glycoprotein (Env) manages to overcome the pressures from all these different host inhibition mechanisms over the long course of viral contamination. HIV-1 Env preserves the resistance to SERINC5 but becomes sensitive to IFITM3 when contamination progresses into the chronic stage. Our study also supports the possibility of using CD4 mimetic compounds to sensitize HIV-1 Env to the inhibition by SERINC5 as a potential therapeutic strategy. 0.05; **, values were calculated with Students test. The values and values of correlation graphs were calculated using correlation Spearman in GraphPad Prism. ACKNOWLEDGMENTS We thank Eric Freed for providing the AD8-1 proviral DNA and the NIH AIDS Reagent Program for providing the Env clones. We are grateful to Myles McLean for crucial readings of the manuscript. This study was supported by funding from the Canadian Institutes of Health Research to C.L. and A.F. (MOP-133479, PJT-166048). A.F. is the recipient of a Canada Research Chair on Retroviral Entry (RCHS0235 950-232424). Recommendations 1. Beitari S, Wang Y, Liu SL, Liang C. 2019. HIV-1 envelope glycoprotein at the interface of host restriction and computer virus evasion. Viruses 11:311. doi:10.3390/v11040311. [PMC free article] [PubMed] [CrossRef] [Google Scholar] 2. Brass AL, Huang IC, Benita Y, John SP, Krishnan MN, Feeley EM, Ryan BJ, Weyer JL, van der Weyden L, Fikrig E, Adams DJ, Xavier RJ, Farzan M, Elledge SJ. 2009. The IFITM proteins mediate cellular resistance to influenza A H1N1 computer virus, West Nile computer virus, and dengue computer virus. Cell 139:1243C1254. doi:10.1016/j.cell.2009.12.017. [PMC free article] [PubMed] [CrossRef] [Google Scholar] 3. Lu J, Pan Q, Rong L, He W, Liu SL, Liang C. 2011. The IFITM proteins inhibit HIV-1 contamination. J Virol 85:2126C2137. doi:10.1128/JVI.01531-10. [PMC free article] [PubMed] [CrossRef] [Google Scholar] 4. Lodermeyer V, Suhr K, Schrott N, Kolbe C, Sturzel CM, Krnavek D, Munch J, Dietz C, Waldmann T, Kirchhoff F, Goffinet C. 2013. 90K, an interferon-stimulated gene product, reduces the infectivity of HIV-1. Retrovirology 10:111. doi:10.1186/1742-4690-10-111. [PMC free article] [PubMed] [CrossRef] [Google Scholar] 5. Wang Q, Zhang X, Han Y, Wang X, Gao G. 2016. M2BP inhibits HIV-1 virion production in a vimentin filaments-dependent manner. Sci Rep 6:32736. doi:10.1038/srep32736. [PMC free article] [PubMed] [CrossRef] [Google Scholar] 6. Lodermeyer V, Ssebyatika G, Passos V, Ponnurangam A, Malassa A, Ewald E, Sturzel CM, Kirchhoff F, Rotger M, Falk CS, Telenti A, Krey T, Goffinet C. 2018. The antiviral activity of the cellular glycoprotein LGALS3BP/90K is usually species specific. J Virol 92 doi:10.1128/JVI.00226-18. [PMC free article] [PubMed] [CrossRef] [Google Scholar] 7. Rosa A, Chande A, Ziglio S, De Sanctis V, Bertorelli R, Goh SL, McCauley SM, Nowosielska A, Antonarakis SE, Luban J, Santoni FA, Pizzato M. 2015. HIV-1 Nef promotes contamination by excluding SERINC5 from virion incorporation. Nature 526:212C217. doi:10.1038/nature15399. [PMC free article] [PubMed] [CrossRef] [Google Scholar] 8. Usami Y, Wu Y, Gottlinger HG. 2015. SERINC3 and SERINC5 restrict HIV-1 infectivity and are counteracted by Nef. Nature 526:218C223. doi:10.1038/nature15400. [PMC free article] [PubMed] [CrossRef] [Google Scholar] 9. Tada T, Zhang Y, Koyama T, Tobiume M, Tsunetsugu-Yokota Y, Yamaoka S, Fujita H, Tokunaga K. 2015. MARCH8 inhibits HIV-1 contamination by reducing.

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