Antiviral activity of the human endogenous retrovirus‐R envelope protein against SARS‐CoV‐2
et al., EMBO Reports, doi:10.15252/embr.202255900, May 2023
In vitro study showing that the HERV-R envelope (HERV-R-Env) protein has antiviral activity against SARS-CoV-2 across multiple different cell-based models.
Ansari et al., 15 May 2023, India, peer-reviewed, 17 authors.
Contact: milan@thsti.res.in.
In vitro studies are an important part of preclinical research, however results may be very different in vivo.
Abstract:
Antiviral activity of the human endogenous retrovirus-R envelope protein against SARS-CoV2
Shabnam Ansari 1 , Nidhi Gupta 1 , † , Rohit Verma 1 , Oinam N Singh 1 , Jyoti Gupta 1 , Amit Kumar 1 , Mukesh Kumar Yadav 1 , Akshay Binayke 2 , Mahima Tiwari 3 , Neha Periwal 4 , Vikas Sood 4 , Shailendra Mani 3 , Amit Awasthi 2 , Shalimar 5 , Baibaswata Nayak 5 , CT Ranjith-Kumar 6 & Milan Surjit 1 ,*
Abstract
Coronavirus-induced disease19 (COVID19 ), caused by SARS-CoV2 , 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-CoV2 -infected cells and observe increased activity of HERV-E, HERV-V, HERV-FRD, HERV-MER 34 , HERV-W, and HERV-K-HML 2 . In contrast, the HERV-R envelope is downregulated in cell-based models and PBMCs of COVID19 patients. Overexpression of HERV-R inhibits SARS-CoV2 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 p 38 MAPK controls the synthesis of the HERV-R envelope protein, which in turn modulates SARSCoV2 replication. These findings suggest the role of the HERV-R envelope as a prosurvival host factor against SARS-CoV2 and illustrate a possible advantage of integration and evolutionary maintenance of retroviral elements in the human genome.
Keywords endogenous retrovirus; endogenous retrovirus envelope; host -pathogen interaction; human endogenous retrovirus-R; SARS-CoV2
Subject Categories
Microbiology, Virology & Host Pathogen Interaction
[EMBO 23 ]; Signal Transduction DOI 10 . 15252 /embr. 202255900 | Received 4 August 2022 | Revised 31 March 2023 | Accepted 26 April 2023 | Published online 15 May 2023
EMBO Reports ( 2023 ) 24 : e 55900
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