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.
【저자키워드】 COVID-19, Innate immunity, AIDS/HIV, 【초록키워드】 SARS-CoV-2, ACE2, TMPRSS2, SARS-COV-2 infection, disease severity, Symptoms, SARS-CoV-2 receptor, Protein, vaccine response, TMPRSS4, ACE2 expression, expression, interferon response, change, single-cell, homeostasis, HIV infection, fatality, GI Tract, antiviral response, mucosal, Gut, epithelial cell, chronic, target cells, reduction, tissue, increased risk, individual, small intestine, SARS-CoV-2 entry receptor, upregulation, downregulation, lymphoid, SARS-CoV-2 nucleocapsid, antiviral genes, infect, uninfected, Prevent, controls, intestinal, highest, analyzed, treated, cause, individuals, impair, Enterocyte, canonical, transcriptional profile, 【제목키워드】 SARS-CoV-2, interferon signaling, HIV infection, target cell, intestinal,