Host-Species Transferrin Receptor 1 Orthologs Are Cellular Receptors for Nonpathogenic New World Clade B Arenaviruses

PLoS Pathogens

Christina F. Spiropoulou¹  Jonathan Abraham²  Jorge Salazar-Bravo²  Jiajie G. Lu²  Michael Farzan³  Hyeryun Choe³  César G. Albariño⁴  Jo Ann Kwong⁵  Sheli R. Radoshitzky⁶ 

[1] Department of Biological Sciences, Texas Tech University, Lubbock, Texas, United States of America;Department of Medicine, Children's Hospital, Harvard Medical School, Boston, Massachusetts, United States of America;Department of Microbiology and Molecular Genetics, Harvard Medical School, New England Primate Center, Southborough, Massachusetts, United States of America;Howard Hughes Medical Institute, Harvard Medical School, Boston, Massachusetts, United States of America;Laboratory of Molecular Medicine, Children's Hospital, Harvard Medical School, Boston, Massachusetts, United States of America;Special Pathogens Branch, Centers for Disease Control and Prevention, Atlanta, Georgia, United States of America

关键词: Arenaviruses;    Hemorrhagic fever viruses;    Chapare virus;    Viral pathogens;    Flow cytometry;    Guanarito virus;    Machupo virus;    Sabiá virus;   

DOI  :  10.1371/journal.ppat.1000358

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

The ability of a New World (NW) clade B arenavirus to enter cells using human transferrin receptor 1 (TfR1) strictly correlates with its ability to cause hemorrhagic fever. Amapari (AMAV) and Tacaribe (TCRV), two nonpathogenic NW clade B arenaviruses that do not use human TfR1, are closely related to the NW arenaviruses that cause hemorrhagic fevers. Here we show that pseudotyped viruses bearing the surface glycoprotein (GP) of AMAV or TCRV can infect cells using the TfR1 orthologs of several mammalian species, including those of their respective natural hosts, the small rodent Neacomys spinosus and the fruit bat Artibeus jamaicensis. Mutation of one residue in human TfR1 makes it a functional receptor for TCRV, and mutation of four residues makes it a functional receptor for AMAV. Our data support an in vivo role for TfR1 in the replication of most, if not all, NW clade B arenaviruses, and suggest that with modest changes in their GPs the nonpathogenic arenaviruses could use human TfR1 and emerge as human pathogens.

【 授权许可】

CC BY