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Signal-regulatory protein alpha is an anti-viral entry factor targeting viruses using endocytic pathways.
Sarute, Nicolás; Cheng, Han; Yan, Zhonghao; Salas-Briceno, Karen; Richner, Justin; Rong, Lijun; Ross, Susan R.
  • Sarute N; University of Illinois at Chicago College of Medicine, Chicago, Illinois, United States of America.
  • Cheng H; University of Illinois at Chicago College of Medicine, Chicago, Illinois, United States of America.
  • Yan Z; University of Illinois at Chicago College of Medicine, Chicago, Illinois, United States of America.
  • Salas-Briceno K; University of Illinois at Chicago College of Medicine, Chicago, Illinois, United States of America.
  • Richner J; University of Illinois at Chicago College of Medicine, Chicago, Illinois, United States of America.
  • Rong L; University of Illinois at Chicago College of Medicine, Chicago, Illinois, United States of America.
  • Ross SR; University of Illinois at Chicago College of Medicine, Chicago, Illinois, United States of America.
PLoS Pathog ; 17(6): e1009662, 2021 06.
Article in English | MEDLINE | ID: covidwho-1259253
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.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: RNA Viruses / Receptors, Immunologic / Endocytosis / Virus Internalization Topics: Vaccines Limits: Animals Language: English Journal: PLoS Pathog Year: 2021 Document Type: Article Affiliation country: Journal.ppat.1009662

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Full text: Available Collection: International databases Database: MEDLINE Main subject: RNA Viruses / Receptors, Immunologic / Endocytosis / Virus Internalization Topics: Vaccines Limits: Animals Language: English Journal: PLoS Pathog Year: 2021 Document Type: Article Affiliation country: Journal.ppat.1009662