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TIM-family proteins inhibit HIV-1 release
Significance TIM-family proteins have been recently shown to promote viral entry into host cells. Unexpectedly, we discovered that human TIM-1, along with TIM-3 and TIM-4, potently inhibits HIV-1 release. We showed that TIM-1 is incorporated into HIV-1 virions and retains HIV-1 particles on the plas...
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| Published in: | Proceedings of the National Academy of Sciences - PNAS 2014-09, Vol.111 (35), p.E3699-E3707 |
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| Language: | English |
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| cites | cdi_FETCH-LOGICAL-c569t-c6b6e2ba129fa23b281a8758ce616a151c0bbee1f459b869f2986603e7b6afb63 |
| container_end_page | E3707 |
| container_issue | 35 |
| container_start_page | E3699 |
| container_title | Proceedings of the National Academy of Sciences - PNAS |
| container_volume | 111 |
| creator | Li, Minghua Ablan, Sherimay D Miao, Chunhui Zheng, Yi-Min Fuller, Matthew S Rennert, Paul D Maury, Wendy Johnson, Marc C Freed, Eric O Liu, Shan-Lu |
| description | Significance TIM-family proteins have been recently shown to promote viral entry into host cells. Unexpectedly, we discovered that human TIM-1, along with TIM-3 and TIM-4, potently inhibits HIV-1 release. We showed that TIM-1 is incorporated into HIV-1 virions and retains HIV-1 particles on the plasma membrane via phosphatidylserine (PS), a phospholipid that is exposed on the cellular plasma membrane and the viral envelope. Expression of TIM-1 inhibits HIV-1 replication in CD4 ⁺ T cells, and knockdown of TIM-3 in monocyte-derived macrophages enhances HIV-1 production. We extended this function of TIMs to other PS receptors, and demonstrated that they also inhibited release of additional viruses, including murine leukemia virus and Ebola virus. The novel role of TIMs in blocking viral release provides new insights into viral replication and AIDS pathogenesis. |
| doi_str_mv | 10.1073/pnas.1404851111 |
| format | article |
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Unexpectedly, we discovered that human TIM-1, along with TIM-3 and TIM-4, potently inhibits HIV-1 release. We showed that TIM-1 is incorporated into HIV-1 virions and retains HIV-1 particles on the plasma membrane via phosphatidylserine (PS), a phospholipid that is exposed on the cellular plasma membrane and the viral envelope. Expression of TIM-1 inhibits HIV-1 replication in CD4 ⁺ T cells, and knockdown of TIM-3 in monocyte-derived macrophages enhances HIV-1 production. We extended this function of TIMs to other PS receptors, and demonstrated that they also inhibited release of additional viruses, including murine leukemia virus and Ebola virus. The novel role of TIMs in blocking viral release provides new insights into viral replication and AIDS pathogenesis.</description><identifier>ISSN: 0027-8424</identifier><identifier>EISSN: 1091-6490</identifier><identifier>DOI: 10.1073/pnas.1404851111</identifier><identifier>PMID: 25136083</identifier><language>eng</language><publisher>United States: National Academy of Sciences</publisher><subject>Biological Sciences ; CD4-Positive T-Lymphocytes - physiology ; CD4-Positive T-Lymphocytes - virology ; Cell Membrane - metabolism ; Cell Membrane - virology ; Cells ; Ebola virus ; Gene expression ; Gene Knockdown Techniques ; HEK293 Cells ; HeLa Cells ; Hepatitis A Virus Cellular Receptor 1 ; Hepatitis A Virus Cellular Receptor 2 ; HIV ; HIV Infections - metabolism ; HIV Infections - virology ; HIV-1 - growth & development ; HIV-1 - metabolism ; Human immunodeficiency virus ; Human immunodeficiency virus 1 ; Humans ; Jurkat Cells ; Membrane Glycoproteins - genetics ; Membrane Glycoproteins - metabolism ; Membrane Proteins - genetics ; Membrane Proteins - metabolism ; Murine leukemia virus ; Mutation ; Phosphatidylserines - metabolism ; PNAS Plus ; Proteins ; Receptors, Virus - genetics ; Receptors, Virus - metabolism ; RNA, Small Interfering - genetics ; Viral infections ; Virion - growth & development ; Virion - metabolism ; Virus Replication - physiology</subject><ispartof>Proceedings of the National Academy of Sciences - PNAS, 2014-09, Vol.111 (35), p.E3699-E3707</ispartof><rights>Copyright National Academy of Sciences Sep 2, 2014</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c569t-c6b6e2ba129fa23b281a8758ce616a151c0bbee1f459b869f2986603e7b6afb63</citedby><cites>FETCH-LOGICAL-c569t-c6b6e2ba129fa23b281a8758ce616a151c0bbee1f459b869f2986603e7b6afb63</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Uhttp://www.pnas.org/content/111/35.cover.gif</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4156686/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4156686/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,314,727,780,784,885,27924,27925,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25136083$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Li, Minghua</creatorcontrib><creatorcontrib>Ablan, Sherimay D</creatorcontrib><creatorcontrib>Miao, Chunhui</creatorcontrib><creatorcontrib>Zheng, Yi-Min</creatorcontrib><creatorcontrib>Fuller, Matthew S</creatorcontrib><creatorcontrib>Rennert, Paul D</creatorcontrib><creatorcontrib>Maury, Wendy</creatorcontrib><creatorcontrib>Johnson, Marc C</creatorcontrib><creatorcontrib>Freed, Eric O</creatorcontrib><creatorcontrib>Liu, Shan-Lu</creatorcontrib><title>TIM-family proteins inhibit HIV-1 release</title><title>Proceedings of the National Academy of Sciences - PNAS</title><addtitle>Proc Natl Acad Sci U S A</addtitle><description>Significance TIM-family proteins have been recently shown to promote viral entry into host cells. Unexpectedly, we discovered that human TIM-1, along with TIM-3 and TIM-4, potently inhibits HIV-1 release. We showed that TIM-1 is incorporated into HIV-1 virions and retains HIV-1 particles on the plasma membrane via phosphatidylserine (PS), a phospholipid that is exposed on the cellular plasma membrane and the viral envelope. Expression of TIM-1 inhibits HIV-1 replication in CD4 ⁺ T cells, and knockdown of TIM-3 in monocyte-derived macrophages enhances HIV-1 production. We extended this function of TIMs to other PS receptors, and demonstrated that they also inhibited release of additional viruses, including murine leukemia virus and Ebola virus. 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Unexpectedly, we discovered that human TIM-1, along with TIM-3 and TIM-4, potently inhibits HIV-1 release. We showed that TIM-1 is incorporated into HIV-1 virions and retains HIV-1 particles on the plasma membrane via phosphatidylserine (PS), a phospholipid that is exposed on the cellular plasma membrane and the viral envelope. Expression of TIM-1 inhibits HIV-1 replication in CD4 ⁺ T cells, and knockdown of TIM-3 in monocyte-derived macrophages enhances HIV-1 production. We extended this function of TIMs to other PS receptors, and demonstrated that they also inhibited release of additional viruses, including murine leukemia virus and Ebola virus. The novel role of TIMs in blocking viral release provides new insights into viral replication and AIDS pathogenesis.</abstract><cop>United States</cop><pub>National Academy of Sciences</pub><pmid>25136083</pmid><doi>10.1073/pnas.1404851111</doi><oa>free_for_read</oa></addata></record> |
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| ispartof | Proceedings of the National Academy of Sciences - PNAS, 2014-09, Vol.111 (35), p.E3699-E3707 |
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| language | eng |
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| source | Open Access: PubMed Central; JSTOR Archival Journals and Primary Sources Collection |
| subjects | Biological Sciences CD4-Positive T-Lymphocytes - physiology CD4-Positive T-Lymphocytes - virology Cell Membrane - metabolism Cell Membrane - virology Cells Ebola virus Gene expression Gene Knockdown Techniques HEK293 Cells HeLa Cells Hepatitis A Virus Cellular Receptor 1 Hepatitis A Virus Cellular Receptor 2 HIV HIV Infections - metabolism HIV Infections - virology HIV-1 - growth & development HIV-1 - metabolism Human immunodeficiency virus Human immunodeficiency virus 1 Humans Jurkat Cells Membrane Glycoproteins - genetics Membrane Glycoproteins - metabolism Membrane Proteins - genetics Membrane Proteins - metabolism Murine leukemia virus Mutation Phosphatidylserines - metabolism PNAS Plus Proteins Receptors, Virus - genetics Receptors, Virus - metabolism RNA, Small Interfering - genetics Viral infections Virion - growth & development Virion - metabolism Virus Replication - physiology |
| title | TIM-family proteins inhibit HIV-1 release |
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