HIV infection drives interferon signaling within intestinal SARS-CoV-2 target cells

Research output: Contribution to journalJournal articleResearchpeer-review


  • Rabiah Fardoos
  • Osaretin E. Asowata
  • Nicholas Herbert
  • Sarah K. Nyquist
  • Yenzekile Zungu
  • Alveera Singh
  • Abigail Ngoepe
  • Ian M. Mbano
  • Ntombifuthi Mthabela
  • Dirhona Ramjit
  • Farina Karim
  • Warren Kuhn
  • Fusi G. Madela
  • Vukani T. Manzini
  • Frank Anderson
  • Bonnie Berger
  • Pers, Tune H
  • Alex K. Shalek
  • Alasdair Leslie
  • Kløverpris, Henrik Nyhus

SARS-CoV-2 infects epithelial cells of the human gastrointestinal (GI) tract and causes related symptoms. HIV infection impairs gut homeostasis and is associated with an increased risk of COVID-19 fatality. To investigate the potential link between these observations, we analyzed singlecell transcriptional profiles and SARS-CoV-2 entry receptor expression across lymphoid and mucosal human tissue from chronically HIV-infected individuals and uninfected controls. Absorptive gut enterocytes displayed the highest coexpression of SARS-CoV-2 receptors ACE2, TMPRSS2, and TMPRSS4, of which ACE2 expression was associated with canonical interferon response and antiviral genes. Chronic treated HIV infection was associated with a clear antiviral response in gut enterocytes and, unexpectedly, with a substantial reduction of ACE2 and TMPRSS2 target cells. Gut tissue from SARS-CoV-2-infected individuals, however, showed abundant SARS-CoV-2 nucleocapsid protein in both the large and small intestine, including an HIV-coinfected individual. Thus, upregulation of antiviral response genes and downregulation of ACE2 and TMPRSS2 in the GI tract of HIV-infected individuals does not prevent SARS-CoV-2 infection in this compartment. The impact of these HIVassociated intestinal mucosal changes on SARS-CoV-2 infection dynamics, disease severity, and vaccine responses remains unclear and requires further investigation.

Original languageEnglish
Article numbere148920
JournalJCI insight
Issue number16
Publication statusPublished - 2021

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