The role of human endogenous retroviruses in melanoma

Abstract

Sequencing of the human genome has established that our DNA harbours many endogenous retrovirus (ERV) sequences, remnants of ancestral exogenous retroviral infections fixed in the germline DNA. In recent years, human ERVs (HERVs) have been implicated in melanomagenesis. Retrovirus-like particles and the expression of HERV mRNA and proteins have been demonstrated in melanoma tissue. In addition, antibodies to HERV proteins have been observed in patients with melanoma. In vitro and mouse models have provided fascinating insights into the potential mechanisms of HERVs in melanomagenesis. This review considers the evidence associating HERVs with melanoma.

Simultaneous Knockdown of Mutant BRAF and Expression of INK4A in Melanoma Cells Leads to Potent Growth Inhibition and Apoptosis

“…For example, syncytin-1 and syncytin-2, encoded by the envelope (ENV) genes of HERV-W and HERV-FRD, respectively, mediate intercellular fusion of trophoblast cells to form syncytiotrophoblast as well as prevent maternal immune attack against the developing embryo, thereby facilitating implantation of the embryo (Krone & Grange, 2010;Rote et al, 2004). It is estimated that 8% of the human genome consists of retroviral elements (Singh et al, 2009). A complete HERV sequence is composed of GAG, POL, and ENV genes flanked by two long terminal repeats (LTRs), similar to exogenous retroviruses such as human immunodeficiency virus (HIV) (Ahn & Kim, 2009).…”

“…Second, HERV-K ENV, which is homologous to syncytin, may have fusogenic activity to mediate melanoma-melanoma and melanoma-target cell intercellular fusions and, therefore, can be the molecular link in the melanoma-normal cell fusion theory of metastasis (Carter, 2008;Pawelek & Chakraborty, 2008). Third, HERV-K proteins can be immunosuppressive (Mangeney et al, 2005) and may facilitate tumor progression by providing a critical survival/escape mechanism for tumor invasion and metastasis (Singh et al, 2009;Voisset et al, 2008), especially in the blood/lymph stream where circulating tumor cells are under attack by the host immune system. HERV-K may prove to be a key mediator of BRAF-MEK-ERK and p16-CDK4-RB pathways d u r i n g m e l a n o m a p a t h o g e n e s i s .…”

Inhibition of Borna disease virus replication by an endogenous bornavirus-like element in the ground squirrel genome

“…Although almost all endogenous retroviruses in animal genomes appear to lack intact ORFs and are not expressed in somatic tissues, some retain the potential to express mRNA and even produce the proteins they encode (2,3). There is mounting evidence that the expression of human endogenous retroviruses (HERVs) is associated with some autoimmune diseases, cancers, and schizophrenia, as well as with viral infections (4)(5)(6), suggesting that the induction of HERVs may be linked to immunological aberrations in the host. In addition, it has been reported that endogenous retroviruses have the ability to recombine with exogenous or other endogenous retroviruses to produce intact infectious viruses (7,8).…”

Melanoma and human papillomaviruses: is there an outlook for study? Review of the literature

“…Находки, сделанные при изучении ассоциаций меланомы с вирусами, обобщались в обзорах S. Singh и соавт. и U. Hengge [19,20].…”