HIV infection drives interferon signaling within intestinal SARS-CoV-2 target cells
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HIV infection drives interferon signaling within intestinal SARS-CoV-2 target cells. / 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 N.
In: JCI insight, Vol. 6, No. 16, e148920, 2021.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - HIV infection drives interferon signaling within intestinal SARS-CoV-2 target cells
AU - Fardoos, Rabiah
AU - Asowata, Osaretin E.
AU - Herbert, Nicholas
AU - Nyquist, Sarah K.
AU - Zungu, Yenzekile
AU - Singh, Alveera
AU - Ngoepe, Abigail
AU - Mbano, Ian M.
AU - Mthabela, Ntombifuthi
AU - Ramjit, Dirhona
AU - Karim, Farina
AU - Kuhn, Warren
AU - Madela, Fusi G.
AU - Manzini, Vukani T.
AU - Anderson, Frank
AU - Berger, Bonnie
AU - Pers, Tune H.
AU - Shalek, Alex K.
AU - Leslie, Alasdair
AU - Kløverpris, Henrik N.
N1 - Funding Information: HNK is supported by the Wellcome Trust (202485/Z/16/Z). AL is supported by the Wellcome Trust (210662/Z/18/Z). This work was supported through the Sub-Saharan African Network for TB/HIV Research Excellence (SANTHE), a DELTAS Africa Initiative (grant DEL-15-006). The DELTAS Africa Initiative is an independent funding scheme of the African Academy of Sciences (AAS) Alliance for Accelerating Excellence in Science in Africa and supported by the New Partnership for Africa’s Development Planning and Coordinating Agency (NEPAD Agency) with funding from the Wellcome Trust (grant 107752/Z/15/Z) and the United Kingdom government. HNK and AS were supported by SANTHE. AKS was supported, in part, by the Searle Scholars Program, the Beckman Young Investigator Program, the NIH (5U24AI118672, 2R01HL095791, 2U19AI089992, 1R01HL134539, 1R01AI138546), a Sloan Fellowship in Chemistry, and the Bill and Melinda Gates Foundation. The views expressed in this publication are those of the authors and not necessarily those of AAS, NEPAD Agency, Wellcome Trust, or the United Kingdom government. Publisher Copyright: © 2021, Fardoos et al.
PY - 2021
Y1 - 2021
N2 - 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.
AB - 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.
U2 - 10.1172/jci.insight.148920
DO - 10.1172/jci.insight.148920
M3 - Journal article
C2 - 34252054
AN - SCOPUS:85113353006
VL - 6
JO - JCI Insight
JF - JCI Insight
SN - 2379-3708
IS - 16
M1 - e148920
ER -
ID: 279195276