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CD169-mediated restrictive SARS-CoV-2 infection of macrophages induces pro-inflammatory responses.
Jalloh, Sallieu; Olejnik, Judith; Berrigan, Jacob; Nisa, Annuurun; Suder, Ellen L; Akiyama, Hisashi; Lei, Maohua; Ramaswamy, Sita; Tyagi, Sanjay; Bushkin, Yuri; Mühlberger, Elke; Gummuluru, Suryaram.
  • Jalloh S; Department of Microbiology, Boston University School of Medicine, Boston, Massachusetts, United States of America.
  • Olejnik J; Department of Microbiology, Boston University School of Medicine, Boston, Massachusetts, United States of America.
  • Berrigan J; National Emerging Infectious Diseases Laboratories, Boston University, Boston, Massachusetts, United States of America.
  • Nisa A; Department of Microbiology, Boston University School of Medicine, Boston, Massachusetts, United States of America.
  • Suder EL; Public Health Research Institute, New Jersey Medical School, Rutgers University, Newark, New Jersey, United States of America.
  • Akiyama H; Department of Microbiology, Boston University School of Medicine, Boston, Massachusetts, United States of America.
  • Lei M; National Emerging Infectious Diseases Laboratories, Boston University, Boston, Massachusetts, United States of America.
  • Ramaswamy S; Department of Microbiology, Boston University School of Medicine, Boston, Massachusetts, United States of America.
  • Tyagi S; Department of Microbiology, Boston University School of Medicine, Boston, Massachusetts, United States of America.
  • Bushkin Y; Department of Microbiology, Boston University School of Medicine, Boston, Massachusetts, United States of America.
  • Mühlberger E; Public Health Research Institute, New Jersey Medical School, Rutgers University, Newark, New Jersey, United States of America.
  • Gummuluru S; Public Health Research Institute, New Jersey Medical School, Rutgers University, Newark, New Jersey, United States of America.
PLoS Pathog ; 18(10): e1010479, 2022 10.
Article in English | MEDLINE | ID: covidwho-2154303
ABSTRACT
Exacerbated and persistent innate immune response marked by pro-inflammatory cytokine expression is thought to be a major driver of chronic COVID-19 pathology. Although macrophages are not the primary target cells of SARS-CoV-2 infection in humans, viral RNA and antigens in activated monocytes and macrophages have been detected in post-mortem samples, and dysfunctional monocytes and macrophages have been hypothesized to contribute to a protracted hyper-inflammatory state in COVID-19 patients. In this study, we demonstrate that CD169, a myeloid cell specific I-type lectin, facilitated ACE2-independent SARS-CoV-2 fusion and entry in macrophages. CD169-mediated SARS-CoV-2 entry in macrophages resulted in expression of viral genomic and subgenomic RNAs with minimal viral protein expression and no infectious viral particle release, suggesting a post-entry restriction of the SARS-CoV-2 replication cycle. Intriguingly this post-entry replication block was alleviated by exogenous ACE2 expression in macrophages. Restricted expression of viral genomic and subgenomic RNA in CD169+ macrophages elicited a pro-inflammatory cytokine expression (TNFα, IL-6 and IL-1ß) in a RIG-I, MDA-5 and MAVS-dependent manner, which was suppressed by remdesivir treatment. These findings suggest that de novo expression of SARS-CoV-2 RNA in macrophages contributes to the pro-inflammatory cytokine signature and that blocking CD169-mediated ACE2 independent infection and subsequent activation of macrophages by viral RNA might alleviate COVID-19-associated hyperinflammatory response.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: COVID-19 Limits: Humans Language: English Journal: PLoS Pathog Year: 2022 Document Type: Article Affiliation country: Journal.ppat.1010479

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Full text: Available Collection: International databases Database: MEDLINE Main subject: COVID-19 Limits: Humans Language: English Journal: PLoS Pathog Year: 2022 Document Type: Article Affiliation country: Journal.ppat.1010479