Interaction of HERVs with PAMPs in Dysregulation of Immune Response Cascade Upon SARS-CoV-2 Infections

Human endogenous retroviruses (HERVs) are genomic fragments integrated into human DNA from germline infections by exogenous retroviruses that threatened primates early in their evolution and are inherited vertically in the germline. So far, HERVs have been studied in the context of extensive immunopathogenic, neuropathogenic and even oncogenic effects within their host. In particular, in our paper, we elaborate on the aspects related to the possible correlation of transposable HERV elements' activation and SARS-CoV-2 spike protein's presence in cells of COVID-19 patients or upon COVID-19 vaccination with implications for natural and adaptive immunity. In particular, the release of cytokines TNF-α, IL-1β and IL-6 occurs in such cases and plays a notable role in sustaining chronic inflammation. Moreover, well-known interindividual variations of HERVs might partially account for the interpersonal variability of COVID-19 symptoms or unwanted events post-vaccination. Accordingly, further studies are required to clarify the SARS-CoV-2 spike protein's role in triggering HERVs.