1887

Journal of General Virology header logo

Volume 101, Issue 5

Parainfluenza virus 5 fusion protein maintains pre-fusion stability but not fusogenic activity following mutation of a transmembrane leucine/isoleucine domain Free

Abstract

The paramyxoviruses Hendra virus (HeV) and parainfluenza virus 5 (PIV5) require the fusion (F) protein to efficiently infect cells. For fusion to occur, F undergoes dramatic, essentially irreversible conformational changes to merge the viral and cell membranes into a continuous bilayer. Recently, a transmembrane (TM) domain leucine/isoleucine (L/I) zipper was shown to be critical in maintaining the expression, stability and pre-fusion conformation of HeV F, allowing for fine-tuned timing of membrane fusion. To analyse the effect of the TM domain L/I zipper in another paramyxovirus, we created alanine mutations to the TM domain of PIV5 F, a paramyxovirus model system. Our data show that while the PIV5 F TM L/I zipper does not significantly affect total expression and only modestly affects surface expression and pre-fusion stability, it is critical for fusogenic activity. These results suggest that the roles of TM L/I zipper motifs differ among members of the family .

  • Received:
  • Accepted:
  • Published Online:
Keyword(s): fusogenic activity , leucine/isoleucine zipper , pre-fusion stability and transmembrane domain
Funding
This study was supported by the:
  • National Institute of General Medical Sciences (Award 2P20 RR02017)
    • Principle Award Recipient: Rebecca Ellis Dutch
  • National Institute of Allergy and Infectious Diseases (Award R01AI051517)
    • Principle Award Recipient: Rebecca Ellis Dutch
© 2020 The Authors
Loading

Article metrics loading...

/content/journal/jgv/10.1099/jgv.0.001399
2020-02-25
2022-05-25
Loading full text...

Full text loading...

/deliver/fulltext/jgv/101/5/467.html?itemId=/content/journal/jgv/10.1099/jgv.0.001399&mimeType=html&fmt=ahah

References

  1. Rima B, Collins P, Easton A, Fouchier R, Kurath G et al. Problems of classification in the family Paramyxoviridae. Arch Virol 2018; 163:1395–1404 [View Article][PubMed]
     [Google Scholar]
  2. Cox RM, Plemper RK. Structure and organization of paramyxovirus particles. Curr Opin Virol 2017; 24:105–114 [View Article][PubMed]
     [Google Scholar]
  3. Harrison MS, Sakaguchi T, Schmitt AP. Paramyxovirus assembly and budding: building particles that transmit infections. Int J Biochem Cell Biol 2010; 42:1416–1429 [View Article][PubMed]
     [Google Scholar]
  4. Smith EC, Smith SE, Carter JR, Webb SR, Gibson KM et al. Trimeric transmembrane domain interactions in paramyxovirus fusion proteins: roles in protein folding, stability, and function. J Biol Chem 2013; 288:35726–35735 [View Article][PubMed]
     [Google Scholar]
  5. Aguilar HC, Henderson BA, Zamora JL, Johnston GP. Paramyxovirus glycoproteins and the membrane fusion process. Curr Clin Microbiol Rep 2016; 3:142–154 [View Article][PubMed]
     [Google Scholar]
  6. Martens S, McMahon HT. Mechanisms of membrane fusion: disparate players and common principles. Nat Rev Mol Cell Biol 2008; 9:543–556 [View Article][PubMed]
     [Google Scholar]
  7. El Najjar F, Schmitt AP, Dutch RE. Paramyxovirus glycoprotein incorporation, assembly and budding: a three way dance for infectious particle production. Viruses 2014; 6:3019–3054 [View Article][PubMed]
     [Google Scholar]
  8. Kim YH, Donald JE, Grigoryan G, Leser GP, Fadeev AY et al. Capture and imaging of a prehairpin fusion intermediate of the paramyxovirus PIV5. Proc Natl Acad Sci USA 2011; 108:20992–20997 [View Article][PubMed]
     [Google Scholar]
  9. Chang A, Dutch RE. Paramyxovirus fusion and entry: multiple paths to a common end. Viruses 2012; 4:613–636 [View Article][PubMed]
     [Google Scholar]
  10. Yao H, Hong M. Membrane-Dependent conformation, dynamics, and lipid interactions of the fusion peptide of the paramyxovirus PIV5 from solid-state NMR. J Mol Biol 2013; 425:563–576 [View Article][PubMed]
     [Google Scholar]
  11. Smith EC, Gregory SM, Tamm LK, Creamer TP, Dutch RE. Role of sequence and structure of the Hendra fusion protein fusion peptide in membrane fusion. J Biol Chem 2012; 287:30035–30048 [View Article][PubMed]
     [Google Scholar]
  12. Pager CT, Craft WW, Patch J, Dutch RE. A mature and fusogenic form of the Nipah virus fusion protein requires proteolytic processing by cathepsin L. Virology 2006; 346:251–257 [View Article][PubMed]
     [Google Scholar]
  13. Welch BD, Liu Y, Kors CA, Leser GP, Jardetzky TS et al. Structure of the cleavage-activated prefusion form of the parainfluenza virus 5 fusion protein. Proc Natl Acad Sci USA 2012; 109:16672–16677 [View Article][PubMed]
     [Google Scholar]
  14. Webb S, Nagy T, Moseley H, Fried M, Dutch R. Hendra virus fusion protein transmembrane domain contributes to pre-fusion protein stability. J Biol Chem 2017; 292:5685–5694 [View Article][PubMed]
     [Google Scholar]
  15. Leyrer S, Bitzer M, Lauer U, Kramer J, Neubert WJ et al. Sendai virus-like particles devoid of haemagglutinin-neuraminidase protein infect cells via the human asialoglycoprotein receptor. J Gen Virol 1998; 79 (Pt 4:683–687 [View Article][PubMed]
     [Google Scholar]
  16. Smith EC, Popa A, Chang A, Masante C, Dutch RE. Viral entry mechanisms: the increasing diversity of paramyxovirus entry. Febs J 2009; 276:7217–7227 [View Article][PubMed]
     [Google Scholar]
  17. Lee JK, Prussia A, Paal T, White LK, Snyder JP et al. Functional interaction between paramyxovirus fusion and attachment proteins. J Biol Chem 2008; 283:16561–16572 [View Article][PubMed]
     [Google Scholar]
  18. Bose S, Heath CM, Shah PA, Alayyoubi M, Jardetzky TS et al. Mutations in the parainfluenza virus 5 fusion protein reveal domains important for fusion triggering and metastability. J Virol 2013; 87:13520–13531 [View Article][PubMed]
     [Google Scholar]
  19. Webb SR, Smith SE, Fried MG, Dutch RE. Transmembrane domains of highly pathogenic viral fusion proteins exhibit trimeric association in vitro . mSphere 2018; 3:e00047-18 [View Article][PubMed]
     [Google Scholar]
  20. Barrett CT, Webb SR, Dutch RE. A hydrophobic target: using the paramyxovirus fusion protein transmembrane domain to modulate fusion protein stability. J Virol 2019; 93: [View Article][PubMed]
     [Google Scholar]
  21. Bissonnette MLZ, Donald JE, DeGrado WF, Jardetzky TS, Lamb RA. Functional analysis of the transmembrane domain in paramyxovirus F protein-mediated membrane fusion. J Mol Biol 2009; 386:14–36 [View Article][PubMed]
     [Google Scholar]
  22. Donald JE, Zhang Y, Fiorin G, Carnevale V, Slochower DR et al. Transmembrane orientation and possible role of the fusogenic peptide from parainfluenza virus 5 (PIV5) in promoting fusion. Proc Natl Acad Sci USA 2011; 108:3958–3963 [View Article][PubMed]
     [Google Scholar]
  23. Porotto M, Yokoyama CC, Palermo LM, Mungall B, Aljofan M et al. Viral entry inhibitors targeted to the membrane site of action. J Virol 2010; 84:6760–6768 [View Article][PubMed]
     [Google Scholar]
  24. Poor TA, Jones LM, Sood A, Leser GP, Plasencia MD et al. Probing the paramyxovirus fusion (F) protein-refolding event from pre- to postfusion by oxidative footprinting. Proc Natl Acad Sci USA 2014; 111:E2596–E2605 [View Article][PubMed]
     [Google Scholar]
  25. Lai AL, Freed JH. The interaction between influenza HA fusion peptide and transmembrane domain affects membrane structure. Biophys J 2015; 109:2523–2536 [View Article][PubMed]
     [Google Scholar]
  26. Lee J, Nyenhuis DA, Nelson EA, Cafiso DS, White JM et al. Structure of the Ebola virus envelope protein MPER/TM domain and its interaction with the fusion loop explains their fusion activity. Proc Natl Acad Sci U S A 2017; 114:E7987–E7996 [View Article][PubMed]
     [Google Scholar]
  27. Kwon B, Lee M, Waring AJ, Hong M. Oligomeric structure and three-dimensional fold of the HIV gp41 membrane-proximal external region and transmembrane domain in phospholipid bilayers. J Am Chem Soc 2018; 140:8246–8259 [View Article][PubMed]
     [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/jgv.0.001399
Loading
Parainfluenza virus 5 fusion protein maintains pre-fusion stability but not fusogenic activity following mutation of a transmembrane leucine/isoleucine domain
J. Gen. Virol. 101, 467 (2020); https://doi.org/10.1099/jgv.0.001399
/content/journal/jgv/10.1099/jgv.0.001399
/content/journal/jgv/10.1099/jgv.0.001399
Loading

Data & Media loading...

Most cited this month Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error