TIM-family proteins inhibit HIV-1 release

• Published in: Proceedings of the National Academy of Sciences - PNAS 2014-09, Vol.111 (35), p.E3699-E3707
• Main Authors: 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
• Format: Article
• Language: English
• 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
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.1404851111

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.