Cysteines Flanking the Internal Fusion Peptide Are Required for the Avian Sarcoma/leukosis Virus Glycoprotein to Mediate the Lipid Mixing Stage of Fusion with High Efficiency

Overview

Journal J Virol

Publisher American Society for Microbiology

Date 2008 Jan 11

PMID 18184714

Citations 12

Authors

Sue E Delos

Matthew B Brecher

Zaoying Chen

Deborah C Melder

Mark J Federspiel

Judith M White

Affiliations

Soon will be listed here.

Abstract

We previously showed that the cysteines flanking the internal fusion peptide of the avian sarcoma/leukosis virus subtype A (ASLV-A) Env (EnvA) are important for infectivity and cell-cell fusion. Here we define the stage of fusion at which the cysteines are required. The flanking cysteines are dispensable for receptor-triggered membrane association but are required for the lipid mixing step of fusion, which, interestingly, displays a high pH onset and a biphasic profile. Second-site mutations that partially restore infection partially restore lipid mixing. These findings indicate that the cysteines flanking the internal fusion peptide of EnvA (and perhaps by analogy Ebola virus glycoprotein) are important for the foldback stage of the conformational changes that lead to membrane merger.

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References

Federspiel M, Hughes S . Retroviral gene delivery. Methods Cell Biol. 1997; 52:179-214. View

Landau N, Littman D . Packaging system for rapid production of murine leukemia virus vectors with variable tropism. J Virol. 1992; 66(8):5110-3. PMC: 241381. DOI: 10.1128/JVI.66.8.5110-5113.1992. View

Takada A, Robison C, Goto H, Sanchez A, Murti K, Whitt M . A system for functional analysis of Ebola virus glycoprotein. Proc Natl Acad Sci U S A. 1998; 94(26):14764-9. PMC: 25111. DOI: 10.1073/pnas.94.26.14764. View

Weissenhorn W, Carfi A, Lee K, Skehel J, Wiley D . Crystal structure of the Ebola virus membrane fusion subunit, GP2, from the envelope glycoprotein ectodomain. Mol Cell. 1998; 2(5):605-16. DOI: 10.1016/s1097-2765(00)80159-8. View

Baker K, Dutch R, Lamb R, Jardetzky T . Structural basis for paramyxovirus-mediated membrane fusion. Mol Cell. 1999; 3(3):309-19. DOI: 10.1016/s1097-2765(00)80458-x. View

Ito H, Watanabe S, Sanchez A, Whitt M, Kawaoka Y . Mutational analysis of the putative fusion domain of Ebola virus glycoprotein. J Virol. 1999; 73(10):8907-12. PMC: 112919. DOI: 10.1128/JVI.73.10.8907-8912.1999. View

Netter R, Amberg S, Balliet J, Biscone M, Vermeulen A, Earp L . Heptad repeat 2-based peptides inhibit avian sarcoma and leukosis virus subgroup a infection and identify a fusion intermediate. J Virol. 2004; 78(24):13430-9. PMC: 533931. DOI: 10.1128/JVI.78.24.13430-13439.2004. View

Melikyan G, Barnard R, Abrahamyan L, Mothes W, Young J . Imaging individual retroviral fusion events: from hemifusion to pore formation and growth. Proc Natl Acad Sci U S A. 2005; 102(24):8728-33. PMC: 1150829. DOI: 10.1073/pnas.0501864102. View

Schornberg K, Matsuyama S, Kabsch K, Delos S, Bouton A, White J . Role of endosomal cathepsins in entry mediated by the Ebola virus glycoprotein. J Virol. 2006; 80(8):4174-8. PMC: 1440424. DOI: 10.1128/JVI.80.8.4174-4178.2006. View

10.

Delos S, Gilbert J, White J . The central proline of an internal viral fusion peptide serves two important roles. J Virol. 2000; 74(4):1686-93. PMC: 111643. DOI: 10.1128/jvi.74.4.1686-1693.2000. View

11.

Delos S, White J . Critical role for the cysteines flanking the internal fusion peptide of avian sarcoma/leukosis virus envelope glycoprotein. J Virol. 2000; 74(20):9738-41. PMC: 112407. DOI: 10.1128/jvi.74.20.9738-9741.2000. View

12.

Armstrong R, KUSHNIR A, White J . The transmembrane domain of influenza hemagglutinin exhibits a stringent length requirement to support the hemifusion to fusion transition. J Cell Biol. 2000; 151(2):425-37. PMC: 2192652. DOI: 10.1083/jcb.151.2.425. View

13.

Mothes W, Boerger A, Narayan S, Cunningham J, Young J . Retroviral entry mediated by receptor priming and low pH triggering of an envelope glycoprotein. Cell. 2000; 103(4):679-89. DOI: 10.1016/s0092-8674(00)00170-7. View

14.

Jeffers S, Sanders D, Sanchez A . Covalent modifications of the ebola virus glycoprotein. J Virol. 2002; 76(24):12463-72. PMC: 136726. DOI: 10.1128/jvi.76.24.12463-12472.2002. View

15.

Earp L, Delos S, Netter R, Bates P, White J . The avian retrovirus avian sarcoma/leukosis virus subtype A reaches the lipid mixing stage of fusion at neutral pH. J Virol. 2003; 77(5):3058-66. PMC: 149735. DOI: 10.1128/jvi.77.5.3058-3066.2003. View

16.

Tamm L . Hypothesis: spring-loaded boomerang mechanism of influenza hemagglutinin-mediated membrane fusion. Biochim Biophys Acta. 2003; 1614(1):14-23. DOI: 10.1016/s0005-2736(03)00159-7. View

17.

Park H, Gruenke J, White J . Leash in the groove mechanism of membrane fusion. Nat Struct Biol. 2003; 10(12):1048-53. DOI: 10.1038/nsb1012. View

18.

Melikyan G, Barnard R, Markosyan R, Young J, Cohen F . Low pH is required for avian sarcoma and leukosis virus Env-induced hemifusion and fusion pore formation but not for pore growth. J Virol. 2004; 78(7):3753-62. PMC: 371058. DOI: 10.1128/jvi.78.7.3753-3762.2004. View

19.

Matsuyama S, Delos S, White J . Sequential roles of receptor binding and low pH in forming prehairpin and hairpin conformations of a retroviral envelope glycoprotein. J Virol. 2004; 78(15):8201-9. PMC: 446138. DOI: 10.1128/JVI.78.15.8201-8209.2004. View

20.

Barnard R, Narayan S, Dornadula G, Miller M, Young J . Low pH is required for avian sarcoma and leukosis virus Env-dependent viral penetration into the cytosol and not for viral uncoating. J Virol. 2004; 78(19):10433-41. PMC: 516436. DOI: 10.1128/JVI.78.19.10433-10441.2004. View