Human Cytomegalovirus Infection of Epithelial Cells Increases SARS-CoV-2 Superinfection by Upregulating the ACE2 Receptor
Marianne Perera, Edward JD Greenwood, Thomas W. M. Crozier, Elizabeth Elder, Janika Schmitt, Colin M. Crump, Paul J Lehner, Mark R. Wills, John Sinclair, Stephen Baker, John R. Bradley, Gordon Dougan, Christoph Hess, Ian Goodfellow, Ravi Gupta, Nathalie Kingston, Paul J Lehner, Paul Lyons, Nicholas J. Matheson, Willem H. Owehand, Caroline Saunders, Kenneth G. C. Smith, Charlotte Summers, James Thaventhiran, Mark Toshner, Michael P. Weekes, Ashlea Bucke, Jo Calder, Laura Canna, Jason Domingo, Anne Elmer, Stewart Fuller, Julie R. Harris, Sarah Hewitt, Jane Kennet, Sherly Jose, Jenny Kourampa, Anne Meadows, Criona O’Brien, Jane Price, Cherry Publico, Rebecca Rastall, Carla M. S. Ribeiro, Jane Rowlands, Valentina Ruffolo, Hugo Tordesillas, Ben Bullman, Benjamin J. Dunmore, Stuart Fawke, Stefan Ting Graf, Josh Hodgson, Christopher Huang, Kelvin Hunter, Emma Jones, Ekaterina Legchenko, Cecilia Matara, Jennifer Martin, Ciara O’Donnell, Linda Pointon, Nicole Pond, Joy Shih, Rachel Sutcliffe, Tobias Tilly, Carmen Treacy, Zhen Tong, Jennifer Wood, Marta Wylot, Laura Bergamaschi, Ariana Betancourt, Georgie Bower, Aloka De, Madeline Epping, Stuart Fawke, Oisín Huhn, Sarah Jackson, Isobel Jarvis, Jimmy Marsden, Francesca Nice, Georgina Okecha, Ommar Omarjee, Marianne Perera, Nathan Richoz, Rahul Sharma, Lori Turner, Eckart M. D. D. De Bie, Katherine Bunclark, Maša Josipović, Michael Mackay, Federica Mescia, Alice Michael, Sabrina Rossi, Mayurun Selvan, Sarah Spencer, Cissy Yong, Ali Ansaripour, Alice Michael, Lucy Mwaura, Caroline Patterson, Gary Polwarth, Petra Polgarova
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.