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

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

Online: http://insight.jci.org/articles/view/148920

Issue: JCI Insight. 2021 Aug 23;6(16):e148920.


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 single-cell 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 HIV-associated intestinal mucosal changes on SARS-CoV-2 infection dynamics, disease severity, and vaccine responses remains unclear and requires further investigation. Keywords: AIDS/HIV, COVID-19, Innate immunity.