Skip to main content
bioRxiv
  • Home
  • About
  • Submit
  • ALERTS / RSS
Advanced Search
New Results

TRIM34 acts with TRIM5 to restrict HIV and SIV capsids

View ORCID ProfileMolly Ohainle, Kyusik Kim, Sevnur Keceli, Abby Felton, Ed Campbell, View ORCID ProfileJeremy Luban, View ORCID ProfileMichael Emerman
doi: https://doi.org/10.1101/820886
Molly Ohainle
1Fred Hutch, Divisions of Human Biology and Basic Sciences, Seattle, WA 98109, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Molly Ohainle
  • For correspondence: mohainle@fredhutch.org memerman@fredhutch.org
Kyusik Kim
2Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Sevnur Keceli
3Department of Microbiology and Immunology, Stritch School of Medicine, Loyola University, Chicago, Maywood, IL, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Abby Felton
1Fred Hutch, Divisions of Human Biology and Basic Sciences, Seattle, WA 98109, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Ed Campbell
3Department of Microbiology and Immunology, Stritch School of Medicine, Loyola University, Chicago, Maywood, IL, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Jeremy Luban
2Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Jeremy Luban
Michael Emerman
1Fred Hutch, Divisions of Human Biology and Basic Sciences, Seattle, WA 98109, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Michael Emerman
  • For correspondence: mohainle@fredhutch.org memerman@fredhutch.org
  • Abstract
  • Full Text
  • Info/History
  • Metrics
  • Preview PDF
Loading

Abstract

The HIV-1 capsid protein makes up the core of the virion and plays a critical role in early steps of HIV replication. Due to its exposure in the cytoplasm after entry, HIV capsid is a target for host cell factors that act directly to block infection such as TRIM5 and MxB. Several host proteins also play a role in facilitating infection, including in the protection of HIV-1 capsid from recognition by host cell restriction factors. Through an unbiased screening approach, called HIV-CRISPR, we show that the Cyclophilin A-binding deficient P90A HIV-1 capsid mutant becomes highly-sensitized to TRIM5alpha restriction in IFN-treated cells. Further, the CPSF6-binding deficient, N74D HIV-1 capsid mutant is sensitive to restriction mediated by human TRIM34, a close paralog of the well-characterized HIV restriction factor TRIM5. This restriction occurs at the step of reverse transcription, is independent of interferon stimulation and limits HIV-1 infection in key target cells of HIV infection including CD4+ T cells and monocyte-derived dendritic cells. TRIM34 restriction requires TRIM5alpha as knockout or knockdown of TRIM5alpha results in a loss of antiviral activity. TRIM34 can also restrict some SIV capsids. Through immunofluorescence studies, we show that TRIM34 and TRIM5alpha colocalize to cytoplasmic bodies and are more frequently observed to be associated with infecting N74D capsids than with WT capsids. Our results identify TRIM34 as an HIV-1 CA-targeting restriction factor and highlight the potential role for heteromultimeric TRIM interactions in contributing restriction of HIV-1 infection in human cells.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
Back to top
PreviousNext
Posted October 30, 2019.
Download PDF
Email

Thank you for your interest in spreading the word about bioRxiv.

NOTE: Your email address is requested solely to identify you as the sender of this article.

Enter multiple addresses on separate lines or separate them with commas.
TRIM34 acts with TRIM5 to restrict HIV and SIV capsids
(Your Name) has forwarded a page to you from bioRxiv
(Your Name) thought you would like to see this page from the bioRxiv website.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Share
TRIM34 acts with TRIM5 to restrict HIV and SIV capsids
Molly Ohainle, Kyusik Kim, Sevnur Keceli, Abby Felton, Ed Campbell, Jeremy Luban, Michael Emerman
bioRxiv 820886; doi: https://doi.org/10.1101/820886
Digg logo Reddit logo Twitter logo Facebook logo Google logo LinkedIn logo Mendeley logo
Citation Tools
TRIM34 acts with TRIM5 to restrict HIV and SIV capsids
Molly Ohainle, Kyusik Kim, Sevnur Keceli, Abby Felton, Ed Campbell, Jeremy Luban, Michael Emerman
bioRxiv 820886; doi: https://doi.org/10.1101/820886

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Subject Area

  • Microbiology
Subject Areas
All Articles
  • Animal Behavior and Cognition (4119)
  • Biochemistry (8828)
  • Bioengineering (6532)
  • Bioinformatics (23484)
  • Biophysics (11804)
  • Cancer Biology (9223)
  • Cell Biology (13336)
  • Clinical Trials (138)
  • Developmental Biology (7442)
  • Ecology (11425)
  • Epidemiology (2066)
  • Evolutionary Biology (15173)
  • Genetics (10452)
  • Genomics (14056)
  • Immunology (9187)
  • Microbiology (22198)
  • Molecular Biology (8823)
  • Neuroscience (47625)
  • Paleontology (351)
  • Pathology (1431)
  • Pharmacology and Toxicology (2493)
  • Physiology (3736)
  • Plant Biology (8090)
  • Scientific Communication and Education (1438)
  • Synthetic Biology (2224)
  • Systems Biology (6042)
  • Zoology (1254)