Signal-regulatory protein alpha is an anti-viral entry factor targeting viruses using endocytic pathways

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 stoma...

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Bibliographic Details
Published in:PLoS pathogens 2021-06, Vol.17 (6), p.e1009662-e1009662
Main Authors: Sarute, Nicolás, Cheng, Han, Yan, Zhonghao, Salas-Briceno, Karen, Richner, Justin, Rong, Lijun, Ross, Susan R
Format: Article
Language:English
Subjects:
Animals
Antiviral agents
Antiviral Agents - pharmacology
Biology and life sciences
Care and treatment
Cell Line
Cell Membrane - virology
Cell surface
Cellular signal transduction
Chlorocebus aethiops
Coronaviruses
Development and progression
Drug Delivery Systems
Endocytosis
Endosomes
Experiments
Gene expression
Genetic aspects
Glycoproteins
Health aspects
Herpes viruses
Host-virus relationships
Immune response
Infections
Integrins - immunology
Interleukin 4
Interleukin-4 - pharmacology
Internalization
Kinases
Leukemia
Medicine and Health Sciences
Mice
Mice, Knockout
Mutation
Phagocytosis
Plasma
Protein Domains
Protein transport
Proteins
Public health
Receptors, Immunologic - genetics
Receptors, Immunologic - physiology
Research and analysis methods
RNA Viruses - immunology
Severe acute respiratory syndrome
Severe acute respiratory syndrome coronavirus 2
SHPS-1 protein
Stomatitis
Vaccines
Vector-borne diseases
Vero Cells
Viral diseases
Virus diseases
Virus Internalization
Viruses
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Summary: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.
ISSN:1553-7374
1553-7366
1553-7374
DOI:10.1371/journal.ppat.1009662