Early cytoplasmic uncoating is associated with infectivity of HIV-1

João I. Mamede, Gianguido C. Cianci, Meegan R. Anderson, Thomas J. Hope*

*Corresponding author for this work

Research output: Contribution to journalArticle

40 Scopus citations

Abstract

After fusion, HIV delivers its conical capsid into the cytoplasm. To release the contained reverse-transcribing viral genome, the capsid must disassemble in a process termed uncoating. Defining the kinetics, dynamics, and cellular location of uncoating of virions leading to infection has been confounded by defective, noninfectious particles and the stochastic minefield blocking access to host DNA. We used live-cell fluorescent imaging of intravirion fluid phase markers to monitor HIV-1 uncoating at the individual particle level. We find that HIV-1 uncoating of particles leading to infection is a cytoplasmic process that occurs ∼30 min postfusion. Most, but not all, of the capsid protein is rapidly shed in tissue culture and primary target cells, independent of entry pathway. Extended time-lapse imaging with less than one virion per cell allows identification of infected cells by Gag-GFP expression and directly links individual particle behavior to infectivity, providing unprecedented insights into the biology of HIV infection.

Original languageEnglish (US)
Pages (from-to)E7169-E7178
JournalProceedings of the National Academy of Sciences of the United States of America
Volume114
Issue number34
DOIs
StatePublished - Aug 22 2017

Keywords

  • HIV-1 early steps
  • HIV-1 uncoating
  • Live-cell imaging

ASJC Scopus subject areas

  • General

Fingerprint Dive into the research topics of 'Early cytoplasmic uncoating is associated with infectivity of HIV-1'. Together they form a unique fingerprint.

  • Cite this