Journal article
TIM-family proteins inhibit HIV-1 release
Proceedings of the National Academy of Sciences - PNAS, Vol.111(35), pp.E3699-E3707
09/02/2014
DOI: 10.1073/pnas.1404851111
PMCID: PMC4156686
PMID: 25136083
Abstract
Accumulating evidence indicates that T-cell immunoglobulin (Ig) and mucin domain (TIM) proteins play critical roles in viral infections. Herein, we report that the TIM-family proteins strongly inhibit HIV-1 release, resulting in diminished viral production and replication. Expression of TIM-1 causes HIV-1 Gag and mature viral particles to accumulate on the plasma membrane. Mutation of the phosphatidylserine (PS) binding sites of TIM-1 abolishes its ability to block HIV-1 release. TIM-1, but to a much lesser extent PS-binding deficient mutants, induces PS flipping onto the cell surface; TIM-1 is also found to be incorporated into HIV-1 virions. Importantly, TIM-1 inhibits HIV-1 replication in CD4-positive Jurkat cells, despite its capability of up-regulating CD4 and promoting HIV-1 entry. In addition to TIM-1, TIM-3 and TIM-4 also block the release of HIV-1, as well as that of murine leukemia virus (MLV) and Ebola virus (EBOV); knockdown of TIM-3 in differentiated monocyte-derived macrophages (MDMs) enhances HIV-1 production. The inhibitory effects of TIM-family proteins on virus release are extended to other PS receptors, such as Axl and RAGE. Overall, our study uncovers a novel ability of TIM-family proteins to block the release of HIV-1 and other viruses by interaction with virion- and cell-associated PS. Our work provides new insights into a virus-cell interaction that is mediated by TIMs and PS receptors.
Details
- Title: Subtitle
- TIM-family proteins inhibit HIV-1 release
- Creators
- Minghua Li - Department of Molecular Microbiology and Immunology, Bond Life Sciences Center, University of Missouri, Columbia, MO 65211Sherimay D Ablan - InterActionChunhui Miao - University of MissouriYi-Min Zheng - University of MissouriMatthew S Fuller - University of MissouriPaul D Rennert - Department of Immunotherapy, SugarCone Biotech LLC, Holliston, MA 01746; andWendy Maury - University of Iowa, Microbiology and ImmunologyMarc C Johnson - University of MissouriEric O Freed - InterActionShan-Lu Liu - The Ohio State University
- Resource Type
- Journal article
- Publication Details
- Proceedings of the National Academy of Sciences - PNAS, Vol.111(35), pp.E3699-E3707
- DOI
- 10.1073/pnas.1404851111
- PMID
- 25136083
- PMCID
- PMC4156686
- ISSN
- 0027-8424
- eISSN
- 1091-6490
- Grant note
- R01AI112381 / NIAID NIH HHS R01 GM110776 / NIGMS NIH HHS Intramural NIH HHS R01 AI1077519 / NIAID NIH HHS R21 AI109464 / NIAID NIH HHS R01 AI112381 / NIAID NIH HHS U54 AI057160 / NIAID NIH HHS R56 AI107095 / NIAID NIH HHS R01 AI107759 / NIAID NIH HHS R21 AI105584 / NIAID NIH HHS
- Language
- English
- Date published
- 09/02/2014
- Academic Unit
- Microbiology and Immunology
- Record Identifier
- 9984208551902771
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