RRC ID 65628
Author Sarute N, Cheng H, Yan Z, Salas-Briceno K, Richner J, Rong L, Ross SR.
Title Signal-regulatory protein alpha is an anti-viral entry factor targeting viruses using endocytic pathways.
Journal PLoS Pathog
Abstract Signal-regulatory protein alpha (SIRPA) is a well-known inhibitor of phagocytosis when it complexes with CD47 expressed on target cells. Here we show that SIRPA decreased in vitro infection by a number of pathogenic viruses, including New World and Old world arenaviruses, Zika virus, vesicular stomatitis virus and pseudoviruses bearing the Machupo virus, Ebola virus and SARS-CoV-2 glycoproteins, but not HSV-1, MLV or mNoV. Moreover, mice with targeted mutation of the Sirpa gene that renders it non-functional were more susceptible to infection with the New World arenaviruses Junín virus vaccine strain Candid 1 and Tacaribe virus, but not MLV or mNoV. All SIRPA-inhibited viruses have in common the requirement for trafficking to a low pH endosomal compartment. This was clearly demonstrated with SARS-CoV-2 pseudovirus, which was only inhibited by SIRPA in cells in which it required trafficking to the endosome. Similar to its role in phagocytosis inhibition, SIRPA decreased virus internalization but not binding to cell surface receptors. We also found that increasing SIRPA levels via treatment with IL-4 led to even greater anti-viral activity. These data suggest that enhancing SIRPA's activity could be a target for anti-viral therapies.
Volume 17(6)
Pages e1009662
Published 2021-6-1
DOI 10.1371/journal.ppat.1009662
PMID 34097709
PMC PMC8211255
MeSH Animals Antiviral Agents / pharmacology Cell Line Cell Membrane / virology Chlorocebus aethiops Drug Delivery Systems Endocytosis* Integrins / immunology Interleukin-4 / pharmacology Mice Mice, Knockout Protein Domains RNA Viruses / immunology* Receptors, Immunologic / genetics Receptors, Immunologic / physiology* Vero Cells Virus Internalization*
IF 6.218
Mice RBRC01544