TIM-family proteins inhibit HIV-1 release

• DOI: 10.1073/pnas.1404851111
• Publication Date: 2014-08-19T06:18:04Z
• Authors: Minghua Li; Sherimay D. Ablan; Chunhui Miao; Yi-Min Zheng; Matthew S. Fuller; Paul D. Rennert; Wendy Maury; Marc C. Johnson; Eric O. Freed; Shan-Lu Liu
• Keywords: CD4-Positive T-Lymphocytes; 0301 basic medicine; Membrane Glycoproteins; Cell Membrane; Virion; Membrane Proteins; HIV Infections; Phosphatidylserines; Virus Replication; 3. Good health; Jurkat Cells; 03 medical and health sciences; HEK293 Cells; Gene Knockdown Techniques; HIV-1; Humans; Receptors, Virus; Hepatitis A Virus Cellular Receptor 1; RNA, Small Interfering; Hepatitis A Virus Cellular Receptor 2; HeLa Cells

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.