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Human Cytomegalovirus Infection of Epithelial Cells Increases SARS-CoV-2 Superinfection by Upregulating the ACE2 Receptor.

Accepted version
Peer-reviewed

Type

Article

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Authors

Greenwood, Edward JD 
Crozier, Thomas WM 
Elder, Elizabeth G 
Schmitt, Janika 

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19), has caused widespread morbidity and mortality since its onset in late 2019. Here, we demonstrate that prior infection with human cytomegalovirus (HCMV) substantially increases infection with SARS-CoV-2 in vitro. HCMV is a common herpesvirus carried by 40%-100% of the population, which can reactivate in the lung under inflammatory conditions, such as those resulting from SARS-CoV-2 infection. We show in both endothelial and epithelial cell types that HCMV infection upregulates ACE2, the SARS-CoV-2 cell entry receptor. These observations suggest that HCMV reactivation events in the lung of healthy HCMV carriers could exacerbate SARS-CoV-2 infection and subsequent COVID-19 symptoms. This effect could contribute to the disparity of disease severity seen in ethnic minorities and those with lower socioeconomic status, due to their higher CMV seroprevalence. Our results warrant further clinical investigation as to whether HCMV infection influences the pathogenesis of SARS-CoV-2.

Description

Keywords

ACE2, COVID-19, HCMV, SARS-CoV-2, coinfection, human cytomegalovirus, Humans, SARS-CoV-2, COVID-19, Angiotensin-Converting Enzyme 2, Seroepidemiologic Studies, Superinfection, Peptidyl-Dipeptidase A, Epithelial Cells, Cytomegalovirus Infections

Journal Title

J Infect Dis

Conference Name

Journal ISSN

0022-1899
1537-6613

Volume Title

Publisher

Oxford University Press (OUP)
Sponsorship
Medical Research Council (MR/S00081X/1)
Wellcome Trust (210688/Z/18/Z)
MRC (MR/V011561/1)
MRC