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bioRxiv · 10.1101/2023.03.21.533610

SARS-CoV-2 infection activates endogenous retroviruses of the LTR69 subfamily

Arora, A.·Kolberg, J. E.·Badarinarayan, S. S.·Munot, D.·Mueller, M.·Sauter, D.·Bansal, V.
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Abstract

Accumulating evidence suggests that endogenous retroviruses (ERVs) play an important role in the host response to infection and the development of disease. By combining RNA- and ChIP-sequencing analyses with RT-qPCR, we show that SARS-CoV-2 infection induces the LTR69 subfamily of ERVs, both in vitro and in vivo. Using functional assays, we identified one SARS-CoV-2-activated LTR69 locus, termed Dup69, which exhibits enhancer activity and is responsive to the transcription factors IRF3 and p65/RelA. LTR69-Dup69 is located about 500 bp upstream of a long non-coding RNA gene (ENSG00000289418) and within the PTPRN2 gene encoding a diabetes-associated autoantigen. Both ENSG00000289418 and PTPRN2 showed a significant increase in expression upon SARS-CoV-2 infection. Thus, our study sheds light on the interplay of exogenous with endogenous viruses and helps to understand how ERVs regulate gene expression during infection.

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Arora, A., Kolberg, J. E., Badarinarayan, S. S., Munot, D., Mueller, M., Sauter, D., Bansal, V.. 2023-03-21. SARS-CoV-2 infection activates endogenous retroviruses of the LTR69 subfamily. https://doi.org/10.1101/2023.03.21.533610

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