Mannose receptor is an HIV restriction factor counteracted by Vpr in macrophages
HIV-1 Vpr is necessary for maximal HIV infection and spread in macrophages. Evolutionary conservation of Vpr suggests an important yet poorly understood role for macrophages in HIV pathogenesis. Vpr counteracts a previously unknown macrophage-specific restriction factor that targets and reduces the...
| Main Authors: | , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
eLife Sciences Publications Ltd
2020-03-01
|
| Series: | eLife |
| Subjects: | |
| Online Access: | https://elifesciences.org/articles/51035 |
| _version_ | 1811181513262235648 |
|---|---|
| author | Jay Lubow Maria C Virgilio Madeline Merlino David R Collins Michael Mashiba Brian G Peterson Zana Lukic Mark M Painter Francisco Gomez-Rivera Valeri Terry Gretchen Zimmerman Kathleen L Collins |
| author_facet | Jay Lubow Maria C Virgilio Madeline Merlino David R Collins Michael Mashiba Brian G Peterson Zana Lukic Mark M Painter Francisco Gomez-Rivera Valeri Terry Gretchen Zimmerman Kathleen L Collins |
| author_sort | Jay Lubow |
| collection | DOAJ |
| description | HIV-1 Vpr is necessary for maximal HIV infection and spread in macrophages. Evolutionary conservation of Vpr suggests an important yet poorly understood role for macrophages in HIV pathogenesis. Vpr counteracts a previously unknown macrophage-specific restriction factor that targets and reduces the expression of HIV Env. Here, we report that the macrophage mannose receptor (MR), is a restriction factor targeting Env in primary human monocyte-derived macrophages. Vpr acts synergistically with HIV Nef to target distinct stages of the MR biosynthetic pathway and dramatically reduce MR expression. Silencing MR or deleting mannose residues on Env rescues Env expression in HIV-1-infected macrophages lacking Vpr. However, we also show that disrupting interactions between Env and MR reduces initial infection of macrophages by cell-free virus. Together these results reveal a Vpr-Nef-Env axis that hijacks a host mannose-MR response system to facilitate infection while evading MR’s normal role, which is to trap and destroy mannose-expressing pathogens. |
| first_indexed | 2024-04-11T09:17:30Z |
| format | Article |
| id | doaj.art-dab34256b6bc48c1a51472489e4ec864 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-11T09:17:30Z |
| publishDate | 2020-03-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-dab34256b6bc48c1a51472489e4ec8642022-12-22T04:32:17ZengeLife Sciences Publications LtdeLife2050-084X2020-03-01910.7554/eLife.51035Mannose receptor is an HIV restriction factor counteracted by Vpr in macrophagesJay Lubow0https://orcid.org/0000-0002-7125-453XMaria C Virgilio1https://orcid.org/0000-0002-4940-188XMadeline Merlino2David R Collins3https://orcid.org/0000-0001-7903-346XMichael Mashiba4Brian G Peterson5https://orcid.org/0000-0001-6871-2336Zana Lukic6Mark M Painter7Francisco Gomez-Rivera8Valeri Terry9https://orcid.org/0000-0002-2499-3882Gretchen Zimmerman10https://orcid.org/0000-0002-6014-9101Kathleen L Collins11https://orcid.org/0000-0002-1712-5809Department of Microbiology and Immunology, University of Michigan, Ann Arbor, United StatesCellular and Molecular Biology Program, University of Michigan, Ann Arbor, United StatesDepartment of Internal Medicine, University of Michigan, Ann Arbor, United StatesDepartment of Microbiology and Immunology, University of Michigan, Ann Arbor, United StatesGraduate Program in Immunology, University of Michigan, Ann Arbor, United StatesDepartment of Biological Chemistry, University of Michigan, Ann Arbor, United StatesDepartment of Internal Medicine, University of Michigan, Ann Arbor, United StatesGraduate Program in Immunology, University of Michigan, Ann Arbor, United StatesGraduate Program in Immunology, University of Michigan, Ann Arbor, United StatesDepartment of Internal Medicine, University of Michigan, Ann Arbor, United StatesGraduate Program in Immunology, University of Michigan, Ann Arbor, United StatesCellular and Molecular Biology Program, University of Michigan, Ann Arbor, United States; Department of Internal Medicine, University of Michigan, Ann Arbor, United States; Graduate Program in Immunology, University of Michigan, Ann Arbor, United StatesHIV-1 Vpr is necessary for maximal HIV infection and spread in macrophages. Evolutionary conservation of Vpr suggests an important yet poorly understood role for macrophages in HIV pathogenesis. Vpr counteracts a previously unknown macrophage-specific restriction factor that targets and reduces the expression of HIV Env. Here, we report that the macrophage mannose receptor (MR), is a restriction factor targeting Env in primary human monocyte-derived macrophages. Vpr acts synergistically with HIV Nef to target distinct stages of the MR biosynthetic pathway and dramatically reduce MR expression. Silencing MR or deleting mannose residues on Env rescues Env expression in HIV-1-infected macrophages lacking Vpr. However, we also show that disrupting interactions between Env and MR reduces initial infection of macrophages by cell-free virus. Together these results reveal a Vpr-Nef-Env axis that hijacks a host mannose-MR response system to facilitate infection while evading MR’s normal role, which is to trap and destroy mannose-expressing pathogens.https://elifesciences.org/articles/51035HIVmannose receptorVprNefrestriction factormacrophages |
| spellingShingle | Jay Lubow Maria C Virgilio Madeline Merlino David R Collins Michael Mashiba Brian G Peterson Zana Lukic Mark M Painter Francisco Gomez-Rivera Valeri Terry Gretchen Zimmerman Kathleen L Collins Mannose receptor is an HIV restriction factor counteracted by Vpr in macrophages eLife HIV mannose receptor Vpr Nef restriction factor macrophages |
| title | Mannose receptor is an HIV restriction factor counteracted by Vpr in macrophages |
| title_full | Mannose receptor is an HIV restriction factor counteracted by Vpr in macrophages |
| title_fullStr | Mannose receptor is an HIV restriction factor counteracted by Vpr in macrophages |
| title_full_unstemmed | Mannose receptor is an HIV restriction factor counteracted by Vpr in macrophages |
| title_short | Mannose receptor is an HIV restriction factor counteracted by Vpr in macrophages |
| title_sort | mannose receptor is an hiv restriction factor counteracted by vpr in macrophages |
| topic | HIV mannose receptor Vpr Nef restriction factor macrophages |
| url | https://elifesciences.org/articles/51035 |
| work_keys_str_mv | AT jaylubow mannosereceptorisanhivrestrictionfactorcounteractedbyvprinmacrophages AT mariacvirgilio mannosereceptorisanhivrestrictionfactorcounteractedbyvprinmacrophages AT madelinemerlino mannosereceptorisanhivrestrictionfactorcounteractedbyvprinmacrophages AT davidrcollins mannosereceptorisanhivrestrictionfactorcounteractedbyvprinmacrophages AT michaelmashiba mannosereceptorisanhivrestrictionfactorcounteractedbyvprinmacrophages AT briangpeterson mannosereceptorisanhivrestrictionfactorcounteractedbyvprinmacrophages AT zanalukic mannosereceptorisanhivrestrictionfactorcounteractedbyvprinmacrophages AT markmpainter mannosereceptorisanhivrestrictionfactorcounteractedbyvprinmacrophages AT franciscogomezrivera mannosereceptorisanhivrestrictionfactorcounteractedbyvprinmacrophages AT valeriterry mannosereceptorisanhivrestrictionfactorcounteractedbyvprinmacrophages AT gretchenzimmerman mannosereceptorisanhivrestrictionfactorcounteractedbyvprinmacrophages AT kathleenlcollins mannosereceptorisanhivrestrictionfactorcounteractedbyvprinmacrophages |