Virion stiffness regulates immature HIV-1 entry

Hong Bo Pang, Liron Hevroni, Nitzan Kol, Debra M. Eckert, Marianna Tsvitov, Michael S. Kay, Itay Rousso

Research output: Contribution to journalArticlepeer-review

50 Scopus citations

Abstract

Background: Human immunodeficiency virus type 1 (HIV-1) undergoes a protease-mediated maturation process that is required for its infectivity. Little is known about how the physical properties of viral particles change during maturation and how these changes affect the viral lifecycle. Using Atomic Force Microscopy (AFM), we previously discovered that HIV undergoes a " stiffness switch" , a dramatic reduction in particle stiffness during maturation that is mediated by the viral Envelope (Env) protein.Results: In this study, we show that transmembrane-anchored Env cytoplasmic tail (CT) domain is sufficient to regulate the particle stiffness of immature HIV-1. Using this construct expressed in trans with viral Env lacking the CT domain, we show that increasing particle stiffness reduces viral entry activity in immature virions. A similar effect was also observed for immature HIV-1 pseudovirions containing Env from vesicular stomatitis virus.Conclusions: This linkage between particle stiffness and viral entry activity illustrates a novel level of regulation for viral replication, providing the first evidence for a biological role of virion physical properties and suggesting a new inhibitory strategy.

Original languageEnglish
Article number4
JournalRetrovirology
Volume10
Issue number1
DOIs
StatePublished - 10 Jan 2013

Keywords

  • Atomic force microscopy
  • HIV
  • Maturation
  • Stiffness
  • Viral entry

ASJC Scopus subject areas

  • Virology
  • Infectious Diseases

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