RT Journal Article
SR Electronic
T1 Human endogenous retrovirus-R envelope is a host restriction factor against severe acute respiratory syndrome-coronavirus-2
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2022.08.05.502940
DO 10.1101/2022.08.05.502940
A1 Nidhi Gupta
A1 Shabnam Ansari
A1 Rohit Verma
A1 Oinam N Singh
A1 Mukesh Kumar Yadav
A1 Akshay Binayke
A1 Kamini Jakhar
A1 Shailendra Mani
A1 Amit Awasthi
A1 Shalimar
A1 Baibaswata Nayak
A1 C.T. Ranjith-Kumar
A1 Milan Surjit
YR 2022
UL http://biorxiv.org/content/early/2022/08/05/2022.08.05.502940.abstract
AB Coronavirus induced disease-19 (COVID-19), caused by the SARS-CoV-2 remains a major global health challenge. Human endogenous retroviruses (HERVs) represent retroviral elements that got integrated into the ancestral human genome. HERVs are important in development and diseases, including cancer, inflammation and viral infections. Here, we analyzed the expression of several HERVs in SARS-CoV-2 infected cells and observed increased activity of HERV-E, HERV-V, HERV-FRD, HERV-MER34, HERV-W and HERV-KHML2. In contrast, HERV-R-envelope was downregulated in cell-based models and COVID-19 patient PBMCs. HERV-R overexpression inhibited SARS-CoV-2 replication, suggesting its antiviral action. Further studies demonstrated the role of extracellular signal-regulated kinase (ERK) in regulating HERV-R antiviral activity. Cross-talk between the ERK and p38 MAPK controls HERV-R envelope synthesis, which in turn modulates the replication of SARS-CoV-2. These findings establish the importance of HERV-R envelope as a host restriction factor against SARS-CoV-2 and illustrate the advantage of integration and evolutionary maintenance of retroviral-elements in the human genome.