The Inhibition of HIV-1 Entry Imposed by Interferon Inducible Transmembrane Proteins Is Independent of Co-Receptor Usage
Abstract
:1. Introduction
2. Materials and Methods
2.1. Cell Lines and Reagents
2.2. Virus Production
2.3. Stable Cell Line Generation
2.4. Virus Infection
2.5. Flow Cytometry
2.6. Immunoblotting
2.7. Statistical Analysis
3. Results
3.1. Ectopic Expression of IFITMs in U87 Cells Inhibits CXCR4 and CCR5 HIV-1 Entry with Equivalent Efficiency
3.2. Entry of T/F Viruses in U87 Cells Is More Sensitive to Inhibition by IFITM2 and IFITM3 than by IFITM1
3.3. Expression of IFITM Proteins in HuT78, SupT1 and THP-1 Cells Equivalently Inhibits CXCR4 and CCR5 HIV-1 Entry
3.4. Endogenous IFITM Proteins in CD4+ T Cells Play Critical Role in IFN-Mediated Restriction of HIV-1 Replication but Contribute Less at the Entry Level
4. Discussion
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
- Bailey, C.C.; Zhong, G.; Huang, I.C.; Farzan, M. IFITM-family proteins: The cell’s first line of antiviral defense. Annu. Rev. Virol. 2014, 1, 261–283. [Google Scholar] [CrossRef] [PubMed]
- Perreira, J.M.; Chin, C.R.; Feeley, E.M.; Brass, A.L. IFITMs restrict the replication of multiple pathogenic viruses. J. Mol. Biol. 2013, 425, 4937–4955. [Google Scholar] [CrossRef] [PubMed]
- Lu, J.; Pan, Q.; Rong, L.; He, W.; Liu, S.L.; Liang, C. The IFITM proteins inhibit HIV-1 infection. J. Virol. 2011, 85, 2126–2137. [Google Scholar] [CrossRef] [PubMed]
- Tartour, K.; Appourchaux, R.; Gaillard, J.; Nguyen, X.N.; Durand, S.; Turpin, J.; Beaumont, E.; Roch, E.; Berger, G.; Mahieux, R.; et al. IFITM proteins are incorporated onto HIV-1 virion particles and negatively imprint their infectivity. Retrovirology 2014, 11, 103. [Google Scholar] [CrossRef] [PubMed]
- Compton, A.A.; Bruel, T.; Porrot, F.; Mallet, A.; Sachse, M.; Euvrard, M.; Liang, C.; Casartelli, N.; Schwartz, O. IFITM proteins incorporated into HIV-1 virions impair viral fusion and spread. Cell Host Microbe 2014, 16, 736–747. [Google Scholar] [CrossRef] [PubMed]
- Yu, J.; Li, M.; Wilkins, J.; Ding, S.; Swartz, T.H.; Esposito, A.M.; Zheng, Y.M.; Freed, E.O.; Liang, C.; Chen, B.K.; et al. IFITM proteins restrict HIV-1 infection by antagonizing the envelope glycoprotein. Cell Rep. 2015, 13, 145–156. [Google Scholar] [CrossRef] [PubMed]
- Wang, Y.; Pan, Q.; Ding, S.; Wang, Z.; Yu, J.; Finzi, A.; Liu, S.L.; Liang, C. The V3 loop of HIV-1 Env determines viral susceptibility to IFITM3 impairment of viral infectivity. J. Virol. 2017, 91, e02441-16. [Google Scholar] [CrossRef] [PubMed]
- Foster, T.L.; Wilson, H.; Iyer, S.S.; Coss, K.; Doores, K.; Smith, S.; Kellam, P.; Finzi, A.; Borrow, P.; Hahn, B.H.; et al. Resistance of transmitted founder HIV-1 to IFITM-mediated restriction. Cell Host Microbe 2016, 20, 429–442. [Google Scholar] [CrossRef] [PubMed]
- Qian, J.; Le Duff, Y.; Wang, Y.M.; Pan, Q.H.; Ding, S.L.; Zheng, Y.M.; Liu, S.L.; Liang, C. Primate lentiviruses are differentially inhibited by interferon-induced transmembrane proteins. Virology 2015, 474, 10–18. [Google Scholar] [CrossRef] [PubMed]
- Li, K.; Markosyan, R.M.; Zheng, Y.M.; Golfetto, O.; Bungart, B.; Li, M.; Ding, S.; He, Y.; Liang, C.; Lee, J.C.; et al. IFITM proteins restrict viral membrane hemifusion. PLoS Pathog. 2013, 9, e1003124. [Google Scholar] [CrossRef] [PubMed]
- deCamp, A.; Hraber, P.; Bailer, R.T.; Seaman, M.S.; Ochsenbauer, C.; Kappes, J.; Gottardo, R.; Edlefsen, P.; Self, S.; Tang, H.; et al. Global panel of HIV-1 Env reference strains for standardized assessments of vaccine-elicited neutralizing antibodies. J. Virol. 2014, 88, 2489–2507. [Google Scholar] [CrossRef] [PubMed]
- Cote, M.; Kucharski, T.J.; Liu, S.L. Enzootic nasal tumor virus envelope requires a very acidic pH for fusion activation and infection. J. Virol. 2008, 82, 9023–9034. [Google Scholar] [CrossRef] [PubMed]
- Zhong, P.; Agosto, L.M.; Ilinskaya, A.; Dorjbal, B.; Truong, R.; Derse, D.; Uchil, P.D.; Heidecker, G.; Mothes, W. Cell-to-cell transmission can overcome multiple donor and target cell barriers imposed on cell-free HIV. PLoS ONE 2013, 8, e53138. [Google Scholar] [CrossRef] [PubMed]
- Mazurov, D.; Ilinskaya, A.; Heidecker, G.; Lloyd, P.; Derse, D. Quantitative comparison of HTLV-1 and HIV-1 cell-to-cell infection with new replication dependent vectors. PLoS Pathog. 2010, 6, e1000788. [Google Scholar] [CrossRef] [PubMed]
- Wu, L.; Martin, T.D.; Vazeux, R.; Unutmaz, D.; KewalRamani, V.N. Functional evaluation of DC-sign monoclonal antibodies reveals DC-sign interactions with ICAM-3 do not promote human immunodeficiency virus type 1 transmission. J. Virol. 2002, 76, 5905–5914. [Google Scholar] [CrossRef] [PubMed]
- Brass, A.L.; Huang, I.C.; Benita, Y.; John, S.P.; Krishnan, M.N.; Feeley, E.M.; Ryan, B.J.; Weyer, J.L.; van der Weyden, L.; Fikrig, E.; et al. The IFITM proteins mediate cellular resistance to influenza a H1N1 virus, West Nile virus, and dengue virus. Cell 2009, 139, 1243–1254. [Google Scholar] [CrossRef] [PubMed]
- Shi, G.; Schwartz, O.; Compton, A.A. More than meets the i: The diverse antiviral and cellular functions of interferon-induced transmembrane proteins. Retrovirology 2017, 14, 53. [Google Scholar] [CrossRef] [PubMed]
- Tartour, K.; Nguyen, X.N.; Appourchaux, R.; Assil, S.; Barateau, V.; Bloyet, L.M.; Burlaud Gaillard, J.; Confort, M.P.; Escudero-Perez, B.; Gruffat, H.; et al. Interference with the production of infectious viral particles and bimodal inhibition of replication are broadly conserved antiviral properties of IFITMs. PLoS Pathog. 2017, 13, e1006610. [Google Scholar] [CrossRef] [PubMed]
- Xie, M.R.; Xuan, B.Q.; Shan, J.Y.; Pan, D.; Sun, Y.M.; Shan, Z.; Zhang, J.P.; Yu, D.; Li, B.; Qian, Z.K. Human cytomegalovirus exploits interferon-induced transmembrane proteins to facilitate morphogenesis of the virion assembly compartment. J. Virol. 2015, 89, 3049–3061. [Google Scholar] [CrossRef] [PubMed]
- Zhao, X.; Guo, F.; Liu, F.; Cuconati, A.; Chang, J.; Block, T.M.; Guo, J.T. Interferon induction of IFITM proteins promotes infection by human coronavirus OC43. Proc. Natl. Acad. Sci. USA 2014, 111, 6756–6761. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Schoggins, J.W.; Wilson, S.J.; Panis, M.; Murphy, M.Y.; Jones, C.T.; Bieniasz, P.; Rice, C.M. A diverse range of gene products are effectors of the type I interferon antiviral response. Nature 2011, 472, 481–485. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Wilkins, J.; Zheng, Y.M.; Yu, J.; Liang, C.; Liu, S.L. Nonhuman primate IFITM proteins are potent inhibitors of HIV and SIV. PLoS ONE 2016, 11, e0156739. [Google Scholar] [CrossRef] [PubMed]
- Jia, R.; Pan, Q.; Ding, S.; Rong, L.; Liu, S.L.; Geng, Y.; Qiao, W.; Liang, C. The N-terminal region of IFITM3 modulates its antiviral activity by regulating IFITM3 cellular localization. J. Virol. 2012, 86, 13697–13707. [Google Scholar] [CrossRef] [PubMed]
- Wu, W.L.; Grotefend, C.R.; Tsai, M.T.; Wang, Y.L.; Radic, V.; Eoh, H.; Huang, I.C. Delta20 IFITM2 differentially restricts X4 and R5 HIV-1. Proc. Natl. Acad. Sci. USA 2017, 114, 7112–7117. [Google Scholar] [CrossRef] [PubMed]
- Miyauchi, K.; Kim, Y.; Latinovic, O.; Morozov, V.; Melikyan, G.B. HIV enters cells via endocytosis and dynamin-dependent fusion with endosomes. Cell 2009, 137, 433–444. [Google Scholar] [CrossRef] [PubMed]
- Carter, G.C.; Bernstone, L.; Baskaran, D.; James, W. HIV-1 infects macrophages by exploiting an endocytic route dependent on dynamin, Rac1 and Pak1. Virology 2011, 409, 234–250. [Google Scholar] [CrossRef] [PubMed]
- Herold, N.; Anders-Osswein, M.; Glass, B.; Eckhardt, M.; Muller, B.; Krausslich, H.G. HIV-1 entry in SupT1-R5, CEM-SS, and primary CD4+ T cells occurs at the plasma membrane and does not require endocytosis. J. Virol. 2014, 88, 13956–13970. [Google Scholar] [CrossRef] [PubMed]
- Pelchen-Matthews, A.; Clapham, P.; Marsh, M. Role of CD4 endocytosis in human immunodeficiency virus infection. J. Virol. 1995, 69, 8164–8168. [Google Scholar] [PubMed]
- Herold, N.; Muller, B.; Krausslich, H.G. Reply to “Can HIV-1 entry sites be deduced by comparing bulk endocytosis to functional readouts for viral fusion?”. J. Virol. 2015, 89, 2986–2987. [Google Scholar] [CrossRef] [PubMed]
- Marin, M.; Melikyan, G.B. Can HIV-1 entry sites be deduced by comparing bulk endocytosis to functional readouts for viral fusion? J. Virol. 2015, 89, 2985. [Google Scholar] [CrossRef] [PubMed]
- Compton, A.A.; Roy, N.; Porrot, F.; Billet, A.; Casartelli, N.; Yount, J.S.; Liang, C.; Schwartz, O. Natural mutations in IFITM3 modulate post-translational regulation and toggle antiviral specificity. EMBO Rep. 2016, 17, 1657–1671. [Google Scholar] [CrossRef] [PubMed]
- Jakobsdottir, G.M.; Iliopoulou, M.; Nolan, R.; Alvarez, L.; Compton, A.A.; Padilla-Parra, S. On the whereabouts of HIV-1 cellular entry and its fusion ports. Trends Mol. Med. 2017, 23, 932–944. [Google Scholar] [CrossRef] [PubMed]
- Mudhasani, R.; Tran, J.P.; Retterer, C.; Radoshitzky, S.R.; Kota, K.P.; Altamura, L.A.; Smith, J.M.; Packard, B.Z.; Kuhn, J.H.; Costantino, J.; et al. IFITM-2 and IFITM-3 but not IFITM-1 restrict rift valley fever virus. J. Virol. 2013, 87, 8451–8464. [Google Scholar] [CrossRef] [PubMed]
- Weidner, J.M.; Jiang, D.; Pan, X.B.; Chang, J.; Block, T.M.; Guo, J.T. Interferon-induced cell membrane proteins, IFITM3 and tetherin, inhibit vesicular stomatitis virus infection via distinct mechanisms. J. Virol. 2010, 84, 12646–12657. [Google Scholar] [CrossRef] [PubMed]
- Diamond, M.S.; Farzan, M. The broad-spectrum antiviral functions of IFIT and IFITM proteins. Nat. Rev. Immunol. 2013, 13, 46–57. [Google Scholar] [CrossRef] [PubMed]
- Li, K.; Jia, R.; Li, M.; Zheng, Y.M.; Miao, C.; Yao, Y.; Ji, H.L.; Geng, Y.; Qiao, W.; Albritton, L.M.; et al. A sorting signal suppresses IFITM1 restriction of viral entry. J. Biol. Chem. 2015, 290, 4248–4259. [Google Scholar] [CrossRef] [PubMed]
- Jia, R.; Ding, S.; Pan, Q.; Liu, S.L.; Qiao, W.; Liang, C. The C-terminal sequence of IFITM1 regulates its anti-HIV-1 activity. PLoS ONE 2015, 10, e0118794. [Google Scholar] [CrossRef] [PubMed]
- Fenton-May, A.E.; Dibben, O.; Emmerich, T.; Ding, H.; Pfafferott, K.; Aasa-Chapman, M.M.; Pellegrino, P.; Williams, I.; Cohen, M.S.; Gao, F.; et al. Relative resistance of HIV-1 founder viruses to control by interferon-alpha. Retrovirology 2013, 10, 146. [Google Scholar] [CrossRef] [PubMed]
- Deymier, M.J.; Ende, Z.; Fenton-May, A.E.; Dilernia, D.A.; Kilembe, W.; Allen, S.A.; Borrow, P.; Hunter, E. Heterosexual transmission of subtype C HIV-1 selects consensus-like variants without increased replicative capacity or interferon-alpha resistance. PLoS Pathog. 2015, 11, e1005154. [Google Scholar] [CrossRef] [PubMed]
- Rambaut, A.; Posada, D.; Crandall, K.A.; Holmes, E.C. The causes and consequences of HIV evolution. Nat. Rev. Genet. 2004, 5, 52–61. [Google Scholar] [CrossRef] [PubMed]
- Haase, A.T. Targeting early infection to prevent HIV-1 mucosal transmission. Nature 2010, 464, 217–223. [Google Scholar] [CrossRef] [PubMed]
- Song, H.S.; Hora, B.; Giorgi, E.E.; Kumar, A.; Cai, F.P.; Bhattacharya, T.; Perelson, A.S.; Gao, F. Transmission of multiple HIV-1 subtype c transmitted/founder viruses into the same recipients was not determined by modest phenotypic differences. Sci. Rep. 2016, 6, 38130. [Google Scholar] [CrossRef] [PubMed]
- Oberle, C.S.; Joos, B.; Rusert, P.; Campbell, N.K.; Beauparlant, D.; Kuster, H.; Weber, J.; Schenkel, C.D.; Scherrer, A.U.; Magnus, C.; et al. Tracing HIV-1 transmission: Envelope traits of HIV-1 transmitter and recipient pairs. Retrovirology 2016, 13, 62. [Google Scholar] [CrossRef] [PubMed]
- Kijak, G.H.; Sanders-Buell, E.; Chenine, A.L.; Eller, M.A.; Goonetilleke, N.; Thomas, R.; Leviyang, S.; Harbolick, E.A.; Bose, M.; Pham, P.; et al. Rare HIV-1 transmitted/founder lineages identified by deep viral sequencing contribute to rapid shifts in dominant quasispecies during acute and early infection. PLoS Pathog. 2017, 13, e1006620. [Google Scholar]
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Yu, J.; Liu, S.-L. The Inhibition of HIV-1 Entry Imposed by Interferon Inducible Transmembrane Proteins Is Independent of Co-Receptor Usage. Viruses 2018, 10, 413. https://doi.org/10.3390/v10080413
Yu J, Liu S-L. The Inhibition of HIV-1 Entry Imposed by Interferon Inducible Transmembrane Proteins Is Independent of Co-Receptor Usage. Viruses. 2018; 10(8):413. https://doi.org/10.3390/v10080413
Chicago/Turabian StyleYu, Jingyou, and Shan-Lu Liu. 2018. "The Inhibition of HIV-1 Entry Imposed by Interferon Inducible Transmembrane Proteins Is Independent of Co-Receptor Usage" Viruses 10, no. 8: 413. https://doi.org/10.3390/v10080413
APA StyleYu, J., & Liu, S.-L. (2018). The Inhibition of HIV-1 Entry Imposed by Interferon Inducible Transmembrane Proteins Is Independent of Co-Receptor Usage. Viruses, 10(8), 413. https://doi.org/10.3390/v10080413