Human Cytomegalovirus (HCMV) induces Human Endogenous Retrovirus (HERV) transcription

Abstract

BackgroundEmerging evidence suggests that human cytomegalovirus (HCMV) is highly prevalent in tumours of different origin. This virus is implied to have oncogenic and oncomodulatory functions, through its ability to control host gene expression. Human endogenous retroviruses (HERV) are also frequently active in tumours of different origin, and are supposed to contribute as cofactors to cancer development. Due to the high prevalence of HCMV in several different tumours, and its ability to control host cell gene expression, we sought to define whether HCMV may affect HERV transcription.FindingsInfection of 3 established cancer cell lines, 2 primary glioblastoma cells, endothelial cells from 3 donors and monocytes from 4 donors with HCMV (strains VR 1814 or TB40/F) induced reverse transcriptase (RT) activity in all cells tested, but the response varied between donors. Both, gammaretrovirus-related class I elements HERV-T, HERV-W, HERV-F and ERV-9, and betaretrovirus-related class II elements HML-2 - 4 and HML-7 - 8, as well as spuma-virus related class III elements of the HERV-L group were up-regulated in response to HCMV infection in GliNS1 cells. Up-regulation of HERV activity was more pronounced in cells harbouring active HCMV infection, but was also induced by UV-inactivated virus. The effect was only slightly affected by ganciclovir treatment and was not controlled by the IE72 or IE86 HCMV genes.ConclusionsWithin this brief report we show that HCMV infection induces HERV transcriptional activity in different cell types.

ATM supports gammaherpesvirus replication by attenuating type I interferon pathway

“…ERVs constitute 8% and 10% of human and mouse genomes, respectively (Waterston, Lindblad-Toh et al, 2002; Lander, Linton et al, 2001) and are remnants of ancient retrovirus infection of the germline. Importantly, some of these elements encode a functional RT and increased expression of endogenous retroviruses is observed in several conditions, including cancer and virus infections (Argaw-Denboba, Balestrieri et al, 2017; Johanning, Malouf et al, 2017; Assinger, Yaiw et al, 2013; Mangeney, Pothlichet et al, 2005; Gonzalez-Cao, Iduma et al, 2016). Increased expression of functional RT encoded by ERVs and subsequent generation of single stranded DNA could account for the cytoplasmic DNA observed in ATM deficient conditions.…”

Pathophysiological Role of HERV-W in Schizophrenia

“…Similar activation of the HERV-W may also occur secondary to infection by cytomegalovirus. Assinger et al 70 showed that experimental cytomegalovirus infection of human cells increases expression of several HERV families, including HERV-W. Depending on the tropism of the infective viruses, one can expect local activation and expression of HERV-W elements in different regions.…”

An ancestral retroviral protein identified as a therapeutic target in type-1 diabetes

“…The few copies retaining such capacities are normally silenced, unless transactivated in some pathological conditions. Environmental viruses can trigger the transactivation of members of the HERV-W family, as this has been demonstrated for herpes virus simplex type 1, cytomegalovirus, or EBV (33,60,61). The transactivation of HERV-W by EBV is of particular interest, owing to the recent demonstration that EBV was the only virus found to be associated with T1D in an immunoproteomic array profiling antiviral antibodies of 23 viral strains (62).…”

“…The underlying question is why the HERV-W-env gene has been transcriptionally activated and translated into a pathogenic protein. An explanation relies upon its transactivation and epigenetic dysregulation by infectious agents, as it has already been demonstrated (33,60,61). In T1D, the question of such dysregulation by enterovirus is raised (12), as well as the role of EBV (62).…”