Single-cell analysis of human lung epithelia reveals concomitant expression of the SARS-CoV-2 receptor ACE2 with multiple virus receptors and scavengers in alveolar type II cells

Guangchun Han; Ansam Sinjab; Warapen Treekitkarnmongkol; Patrick Brennan; Kieko Hara; Kyle Chang; Elena Bogatenkova; Beatriz Sanchez-Espiridion; Carmen Behrens; Boning Gao; Luc Girard; Jianjun Zhang; Boris Sepesi; Tina Cascone; Lauren Byers; Don L. Gibbons; Jichao Chen; Seyed Javad Moghaddam; Edwin J. Ostrin; Junya Fujimoto; Jerry Shay; John V. Heymach; John D. Minna; Steven Dubinett; Paul A. Scheet; Ignacio I. Wistuba; Edward Hill; Shannon Telesco; Christopher Stevenson; Avrum E. Spira; Linghua Wang; Humam Kadara

in saliva was shown to exert host defense roles (neutralization or inhibition of oral transmission) against influenza A virus 55 as well as HIV-1 56 . DMBT1 was shown to specifically inhibit HIV-1 infectivity by binding to the virus envelope protein gp120, the same protein that binds to the CD4 receptor on T cells in the host 57 . Intriguingly, very much like emerging reports on ACE2 acting as an entry route in the lung that facilitates SARS-CoV-2 infection 6 , DMBT1 was shown to aid in HIV-1 transcytosis across genital tract tissue 58 . Also, the study by Stoddard and colleagues demonstrated that transport of HIV-1 can be inhibited by antibodies or peptides that block the interaction of DMBT1 with the HIV-1 envelope protein gp120 58 . Given our findings on DMBT1 expression in lung AT2 cells and its co-expression with ACE2, as well as its reported binding with multiple viruses, we suggest that The copyright holder for this preprint (which was not peer-reviewed) is the . https://doi.org/10.1101/2020.04.16.045617 doi: bioRxiv preprint among all lung cell subsets AT2 cells displayed highest relative expression of the SARS-CoV-2 receptor ACE2, albeit at a low cell fraction (~2.2% of all AT2 cells). We found that the viral scavenger DMBT1 is highly expressed in AT2 cells and correlates with ACE2 in this compartment. Our study points to a scarce ACE2-expressing AT2 population that also expresses genes involved in inflammatory lung pathological conditions (e.g., pneumonia) and in host defense and, thus, could be exploited (or repurposed) as phenotypic targets for treatment of SARS-CoV-2 infection and COVID-19 disease.