TIM-family Proteins Promote Infection of Multiple Enveloped Viruses through Virion-associated Phosphatidylserine

PLoS Pathogens

Xia Bu¹  Gordon J. Freeman¹  Sheena Monahan²  Dale T. Umetsu²  Rosemarie H. DeKruyff²  Asim A. Ahmed³  Stephanie Jemielity³  Hyeryun Choe³  Jinyize J. Wang³  Wenhui Li⁴  Michael Farzan⁵  Ying Kai Chan⁵ 

[1] Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, United States of America;Division of Immunology, Children's Hospital Boston, Harvard Medical School, Boston, Massachusetts, United States of America;Division of Respiratory Diseases Children's Hospital Boston, Harvard Medical School, Boston, Massachusetts, United States of America;National Institute of Biological Sciences, Beijing, China;New England Primate Center, Department of Microbiology and Immunobiology, Harvard Medical School, Boston, Massachusetts, United States of America

关键词: 293T cells;    Viral entry;    West Nile virus;    Virions;    Liposomes;    SARS coronavirus;    Antibodies;    Dengue virus;   

DOI  :  10.1371/journal.ppat.1003232

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

Human T-cell Immunoglobulin and Mucin-domain containing proteins (TIM1, 3, and 4) specifically bind phosphatidylserine (PS). TIM1 has been proposed to serve as a cellular receptor for hepatitis A virus and Ebola virus and as an entry factor for dengue virus. Here we show that TIM1 promotes infection of retroviruses and virus-like particles (VLPs) pseudotyped with a range of viral entry proteins, in particular those from the filovirus, flavivirus, New World arenavirus and alphavirus families. TIM1 also robustly enhanced the infection of replication-competent viruses from the same families, including dengue, Tacaribe, Sindbis and Ross River viruses. All interactions between TIM1 and pseudoviruses or VLPs were PS-mediated, as demonstrated with liposome blocking and TIM1 mutagenesis experiments. In addition, other PS-binding proteins, such as Axl and TIM4, promoted infection similarly to TIM1. Finally, the blocking of PS receptors on macrophages inhibited the entry of Ebola VLPs, suggesting that PS receptors can contribute to infection in physiologically relevant cells. Notably, infection mediated by the entry proteins of Lassa fever virus, influenza A virus and SARS coronavirus was largely unaffected by TIM1 expression. Taken together our data show that TIM1 and related PS-binding proteins promote infection of diverse families of enveloped viruses, and may therefore be useful targets for broad-spectrum antiviral therapies.

【 授权许可】

CC BY