HERV reactivation by adenovirus infection is associated with viral immune regulation.

Human endogenous retroviruses (HERVs), which are normally silenced by methylation or mutation, can be reactivated by a variety of environmental factors, including infection with exogenous viruses. In this work, we investigated the transcriptional activity of HERVs following infection of human liver cells (HepaRG) with human adenovirus C serotype 5 (HAdV-C5). HAdV-C5 infection results in reactivation of several HERV groups as well as differentially expressed genes. Interestingly, in HAdV-C5 infection, upregulated genes that were in close chromosomal proximity to upregulated HERV loci were associated with influencing viral carcinogenesis and inflammatory signaling. We also identified an FBXO17 transcript encoding an intronic ERVK9-11 sense sequence upon HAdV-C5 infection. FBXO17 has previously been described as an important factor in the regulation of the interferon response. This suggests that specific HERV groups may have the potential to trigger gene networks and influence viral immune responses.