Human endogenous retroviruses and cancer

Abstract

Human endogenous retroviruses (HERVs) are retroviruses that infected human genome millions of years ago and have persisted throughout human evolution. About 8% of our genome is composed of HERVs, most of which are nonfunctional because of epigenetic control or deactivating mutations. However, a correlation between HERVs and human cancer has been described and many tumors, such as melanoma, breast cancer, germ cell tumors, renal cancer or ovarian cancer, express HERV proteins, mainly HERV-K (HML6) and HERV-K (HML2). Although the causative role of HERVs in cancer is controversial, data from animal models demonstrated that endogenous retroviruses are potentially oncogenic. HERV protein expression in human cells generates an immune response by activating innate and adaptive immunities. Some HERV-derived peptides have antigenic properties. For example, HERV-K (HML-6) encodes the HER-K MEL peptide recognized by CD8+ lymphocytes. In addition, HERVs are two-edged immunomodulators. HERVs show immunosuppressive activity. The presence of genomic retroviral elements in host-cell cytosol may activate an interferon type I response. Therefore, targeting HERVs through cellular vaccines or immunomodulatory drugs combined with checkpoint inhibitors is attracting interest because they could be active in human tumors.

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.…”

Cytotoxic stress induces transfer of mitochondria-associated human endogenous retroviral RNA and proteins between cancer cells

“…However, products of the envelope genes, i.e. syncytins, which are normally restricted to the placenta, have been identified in human malignancies, and it has been suggested that syncytin-mediated cell fusion events play a role in the transformation and metastasis process [ 21 , 24 , 33 , 46 , 57 ].…”

The MeLiM Minipig: An Original Spontaneous Model to Explore Cutaneous Melanoma Genetic Basis

“…The global hypomethylation of the genome observed in many tumors is likely to explain the reactivation of HERV transcription, usually silenced by CpG methylation of the LTRs ( Stengel et al, 2010 ). Among the possible oncogenic mechanisms, HERV-K could participate to cell transformation by insertional mutagenesis, through its rec and np9 oncogenic proteins, or even by modulating the immune response ( Gonzalez-Cao et al, 2016 ). However, even if HERVs are released as particles (which is rarely the case), they remain non-infectious ( Denner, 2016 ).…”