Beyond pathogens: the intriguing genetic legacy of endogenous retroviruses in host physiology.

The notion that viruses played a crucial role in the evolution of life is not a new concept. However, more recent insights suggest that this perception might be even more expansive, highlighting the ongoing impact of viruses on host evolution. Endogenous retroviruses (ERVs) are considered genomic remnants of ancient viral infections acquired throughout vertebrate evolution. Their exogenous counterparts once infected the host's germline cells, eventually leading to the permanent endogenization of their respective proviruses. The success of ERV colonization is evident so that it constitutes 8% of the human genome. Emerging genomic studies indicate that endogenous retroviruses are not merely remnants of past infections but rather play a corollary role, despite not fully understood, in host genetic regulation. This review presents some evidence supporting the crucial role of endogenous retroviruses in regulating host genetics. We explore the involvement of human ERVs (HERVs) in key physiological processes, from their precise and orchestrated activities during cellular differentiation and pluripotency to their contributions to aging and cellular senescence. Additionally, we discuss the costs associated with hosting a substantial amount of preserved viral genetic material.

Association between development of severe COVID-19 and a polymorphism in the CIAS1 gene that codes for an inflammasome component.

An elevated pro-inflammatory cytokine response is associated with severe life-threatening symptoms in individuals with Coronavirus Disease-2019 (COVID). The inflammasome is an intracellular structure responsible for generation of interleukin (IL)-1ß and IL-18. NALP3, a product of the CIAS1 gene, is the rate-limiting component for inflammasome activity. We evaluated if a CIAS1 42 base pair length polymorphism (rs74163773) was associated with severe COVID. DNA from 93 individuals with severe COVID, 38 with mild COVID, and 98 controls were analyzed for this polymorphism. The 12 unit repeat allele is associated with the highest inflammasome activity. Five alleles, corresponding to 6, 7, 9, 12 or 13 repeat units, divided into 12 genotypes were identified. The frequency of the 12 unit repeat allele was 45.3% in those with severe disease as opposed to 30.0% in those with mild disease and 26.0% in controls (p < 0.0001, severe vs. controls). In contrast, the 7 unit repeat allele frequency was 30.1% in controls as opposed to 14.0% and 12.5% in those with severe or mild disease, respectively (p ≤ 0.0017). We conclude that individuals positive for the CIAS1 12 allele may be at elevated risk for development of severe COVID due to an increased level of induced pro-inflammatory cytokine production.