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Identification of a pocket factor that is critical to Zika virus assembly.

DiNunno NM, Goetschius DJ, Narayanan A, Majowicz SA, Moustafa I, Bator CM, Hafenstein SL, Jose J
Nat Commun 11 4953 (2020)
Cited: 17 times
EuropePMC logo PMID: 33009400

Abstract

Zika virus (ZIKV) is an emerging mosquito borne flavivirus and a major public health concern causing severe disease. Due to the presence of a lipid membrane and structural heterogeneity, attaining an atomic resolution structure is challenging, but important to understand virus assembly and life cycle mechanisms that offer distinct targets for therapeutic intervention. We here use subvolume refinement to achieve a 3.4 Å resolution structure and identify two distinct lipid moieties. The first arises from the inner leaflet and is coordinated by hydrophobic residues of the M and E transmembrane helices that form a binding pocket not previously characterized. The second lipid arises from the outer leaflet coordinate between two E protein helices. Structure-based mutagenesis identifies critical hydrophobic interactions and their effect on the virus life cycle. Results show that lipids play an essential role in the ZIKV assembly pathway revealing a potential target of lipid based antiviral drug development.

Reviews citing this publication (4)

  1. Surfactants - Compounds for inactivation of SARS-CoV-2 and other enveloped viruses. Simon M, Veit M, Osterrieder K, Gradzielski M. Curr Opin Colloid Interface Sci 55 101479 (2021)
  2. Protein-driven membrane remodeling: Molecular perspectives from Flaviviridae infections. Campbell O, Monje-Galvan V. Biophys J 122 1890-1899 (2023)
  3. The Japanese Encephalitis Antigenic Complex Viruses: From Structure to Immunity. Khare B, Kuhn RJ. Viruses 14 2213 (2022)
  4. Pathogenesis and virulence of flavivirus infections. van Leur SW, Heunis T, Munnur D, Sanyal S. Virulence 12 2814-2838 (2021)

Articles citing this publication (13)

  1. A unified route for flavivirus structures uncovers essential pocket factors conserved across pathogenic viruses. Hardy JM, Newton ND, Modhiran N, Scott CAP, Venugopal H, Vet LJ, Young PR, Hall RA, Hobson-Peters J, Coulibaly F, Watterson D. Nat Commun 12 3266 (2021)
  2. Flavivirus maturation leads to the formation of an occupied lipid pocket in the surface glycoproteins. Renner M, Dejnirattisai W, Carrique L, Martin IS, Karia D, Ilca SL, Ho SF, Kotecha A, Keown JR, Mongkolsapaya J, Screaton GR, Grimes JM. Nat Commun 12 1238 (2021)
  3. Molecular Organisation of Tick-Borne Encephalitis Virus. Pulkkinen LIA, Barrass SV, Domanska A, Överby AK, Anastasina M, Butcher SJ. Viruses 14 792 (2022)
  4. An Absolutely Conserved Tryptophan in the Stem of the Envelope Protein E of Flaviviruses Is Essential for the Formation of Stable Particles. Medits I, Heinz FX, Stiasny K. Viruses 13 1727 (2021)
  5. Adsorption of pulmonary and exogeneous surfactants on SARS-CoV-2 spike protein. Santo KP, Neimark AV. J Colloid Interface Sci 650 28-39 (2023)
  6. Cryo-EM reveals binding of linoleic acid to SARS-CoV-2 spike glycoprotein, suggesting an antiviral treatment strategy. Toelzer C, Gupta K, Berger I, Schaffitzel C. Acta Crystallogr D Struct Biol 79 111-121 (2023)
  7. Drugs to limit Zika virus infection and implication for maternal-fetal health. Kumar A, Kumar D, Jose J, Giri R, Mysorekar IU. Front Virol 2 928599 (2022)
  8. Identification of a critical role for ZIKV capsid α3 in virus assembly and its genetic interaction with M protein. Jablunovsky A, Narayanan A, Jose J. PLoS Negl Trop Dis 18 e0011873 (2024)
  9. Leu-to-Phe substitution at prM146 decreases the growth ability of Zika virus and partially reduces its pathogenicity in mice. Inagaki T, Taniguchi S, Kawai Y, Maeki T, Nakayama E, Tajima S, Takeyama H, Lim CK, Saijo M. Sci Rep 11 19635 (2021)
  10. Simultaneous membrane and RNA binding by tick-borne encephalitis virus capsid protein. Pulkkinen LIA, Barrass SV, Lindgren M, Pace H, Överby AK, Anastasina M, Bally M, Lundmark R, Butcher SJ. PLoS Pathog 19 e1011125 (2023)
  11. Structure of Usutu virus SAAR-1776 displays fusion loop asymmetry. Khare B, Klose T, Fang Q, Rossmann MG, Kuhn RJ. Proc Natl Acad Sci U S A 118 e2107408118 (2021)
  12. Structure of infective Getah virus at 2.8 Å resolution determined by cryo-electron microscopy. Wang A, Zhou F, Liu C, Gao D, Qi R, Yin Y, Liu S, Gao Y, Fu L, Xia Y, Xu Y, Wang C, Liu Z. Cell Discov 8 12 (2022)
  13. Zika virus prM protein contains cholesterol binding motifs required for virus entry and assembly. Goellner S, Enkavi G, Prasad V, Denolly S, Eu S, Mizzon G, Witte L, Kulig W, Uckeley ZM, Lavacca TM, Haselmann U, Lozach PY, Brügger B, Vattulainen I, Bartenschlager R. Nat Commun 14 7344 (2023)


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