Antiviral activity of the human endogenous retrovirus‐R envelope protein against SARS‐CoV‐2

Author:

Ansari Shabnam1,Gupta Nidhi1,Verma Rohit1ORCID,Singh Oinam N1,Gupta Jyoti1,Kumar Amit1,Yadav Mukesh Kumar1,Binayke Akshay2ORCID,Tiwari Mahima3ORCID,Periwal Neha4,Sood Vikas4ORCID,Mani Shailendra3ORCID,Awasthi Amit2,Shalimar 5,Nayak Baibaswata5,Ranjith‐Kumar CT6,Surjit Milan1ORCID

Affiliation:

1. Virology Laboratory Translational Health Science and Technology Institute, NCR Biotech Science Cluster Faridabad India

2. Immunobiology Laboratory Translational Health Science and Technology Institute, NCR Biotech Science Cluster Faridabad India

3. Translational Health Science and Technology Institute, NCR Biotech Science Cluster Faridabad India

4. Department of Biochemistry, School of Chemical and Life Sciences Jamia Hamdard University New Delhi India

5. Department of Gastroenterology All India Institute of Medical Sciences New Delhi India

6. University School of Biotechnology, Guru Gobind Singh Indraprastha University New Delhi India

Abstract

AbstractCoronavirus‐induced disease‐19 (COVID‐19), caused by SARS‐CoV‐2, is still a major global health challenge. Human endogenous retroviruses (HERVs) represent retroviral elements that were integrated into the ancestral human genome. HERVs are important in embryonic development as well as in the manifestation of diseases, including cancer, inflammation, and viral infections. Here, we analyze the expression of several HERVs in SARS‐CoV‐2‐infected cells and observe increased activity of HERV‐E, HERV‐V, HERV‐FRD, HERV‐MER34, HERV‐W, and HERV‐K‐HML2. In contrast, the HERV‐R envelope is downregulated in cell‐based models and PBMCs of COVID‐19 patients. Overexpression of HERV‐R inhibits SARS‐CoV‐2 replication, suggesting its antiviral activity. Further analyses demonstrate the role of the extracellular signal‐regulated kinase (ERK) in regulating HERV‐R antiviral activity. Lastly, our data indicate that the crosstalk between ERK and p38 MAPK controls the synthesis of the HERV‐R envelope protein, which in turn modulates SARS‐CoV‐2 replication. These findings suggest the role of the HERV‐R envelope as a prosurvival host factor against SARS‐CoV‐2 and illustrate a possible advantage of integration and evolutionary maintenance of retroviral elements in the human genome.

Funder

Department of Biotechnology, Ministry of Science and Technology, India

Science and Engineering Research Board

Publisher

Springer Science and Business Media LLC

Subject

Genetics,Molecular Biology,Biochemistry

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