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Author Notes:

E-mail: paul.spearman@emory.edu

Conceived and designed the experiments: XW LD PS. Performed the experiments: XW LD. Analyzed the data: XW LD EH PS. Contributed reagents/materials/analysis tools: XW EH. Wrote the paper: XW PS.

The authors have declared that no competing interests exist.

Subjects:

Research Funding:

This work was supported by National Institutes of Health grant GM-111027 (PS) and CA-27834 (EH). Supporting infrastructure was provided by funds from Children's Healthcare of Atlanta, the Children's Center for Immunology and Vaccines, and the Emory Center for AIDS Research (P30 AI050409). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Keywords:

  • Science & Technology
  • Multidisciplinary Sciences
  • Science & Technology - Other Topics
  • PFIZER MONKEY VIRUS
  • INTERACTION NETWORKS
  • CELLULAR-PROTEINS
  • PLASMA-MEMBRANE
  • HOST PROTEINS
  • ESCRT PATHWAY
  • GAG PROTEINS
  • TYPE-1
  • ACTIN
  • REPLICATION

An siRNA Screen of Membrane Trafficking Genes Highlights Pathways Common to HIV-1 and M-PMV Virus Assembly and Release

Tools:

Journal Title:

PLoS ONE

Volume:

Volume 9, Number 9

Publisher:

, Pages e106151-e106151

Type of Work:

Article | Final Publisher PDF

Abstract:

The assembly and release of retroviruses from the host cells requires a coordinated series of interactions between viral structural proteins and cellular trafficking pathways. Although a number of cellular factors involved in retrovirus assembly have been identified, it is likely that retroviruses utilize additional trafficking factors to expedite their assembly and budding that have not yet been defined. We performed a screen using an siRNA library targeting host membrane trafficking genes in order to identify new host factors that contribute to retrovirus assembly or release. We utilized two retroviruses that follow very distinct assembly pathways, HIV-1 and Mason-Pfizer monkey virus (M-PMV) in order to identify host pathways that are generally applicable in retrovirus assembly versus those that are unique to HIV or M-PMV. Here we report the identification of 24 host proteins identified in the screen and subsequently validated in follow-up experiments as contributors to the assembly or release of both viruses. In addition to identifying a number of previously unsuspected individual trafficking factors, we noted multiple hits among proteins involved in modulation of the actin cytoskeleton, clathrin-mediated transport pathways, and phosphoinositide metabolism. Our study shows that distant genera of retroviruses share a number of common interaction strategies with host cell trafficking machinery, and identifies new cellular factors involved in the late stages of retroviral replication.

Copyright information:

© 2014 Wen et al.

This is an Open Access article distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits distribution of derivative works, distribution, public display, and publicly performance, making multiple copies, provided the original work is properly cited. This license requires copyright and license notices be kept intact, credit be given to copyright holder and/or author.

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