The multiple sclerosis-associated retrovirus and its HERV-W endogenous family: a biological interface between virology, genetics, and immunology in human physiology and disease

Abstract

This mini-review summarizes current knowledge of MSRV (multiple sclerosis-associated retrovirus), founder member of the type W family of human endogenous retroviruses (HERVs), its pathogenic potential and association with diseases. As retrotransposable elements, HERVs behave differently from stable genes, and cannot be studied with "Mendelian genetics" concepts only. They also display complex interactions with other HERV families, and with classical viruses. These concepts may contribute to unravelling the etiopathogenesis of complex diseases such as multiple sclerosis, schizophrenia, and other chronic multifactorial diseases.

Neuroinflammation and Endoplasmic Reticulum Stress Are Coregulated by Crocin To Prevent Demyelination and Neurodegeneration

“…Several exogenous and endogenous infectious agents have been implicated in MS pathogenesis including human herpes viruses, human coronaviruses, and human endogenous retroviruses (HERVs) (21). Among the HERVs, the MS retrovirus, HERV-H, and the HERV-W envencoded glycoprotein, Syncytin-1, have been reported to participate in MS neuropathogenesis (22)(23)(24)(25)(26). Syncytin-1, encoded by the HERV-W env gene, ERVWE1, on chromosome 7q21.2 is expressed in the placenta, and its role in health is likely to mediate syncytial fusion of the villous trophoblast (27).…”

The aliens inside human DNA: HERV-W/MSRV/syncytin-1 endogenous retroviruses and neurodegeneration

“…MSRV might be either an exogenous HERV-W, or a non-ubiquitous replication-competent member, or a partly defective, non-ubiquitous copy, seldom complemented or recombined within the HERV-W family [24]. Whatever the origin of MSRV, ~9% of healthy Caucasians have circulating virionic MSRV/HERV-W RNA [16].…”

“…There have been two milestone discoveries about HERV-W: the discovery of its founder member, the multiple sclerosis (MS)-associated retrovirus (MSRV, a presumably complete virus, since it is able to form extracellular, infectious virions), released by leptomeningeal cells of MS patients [16][17], and the discovery that syncytin-1 (a protein expressed in human placenta during pregnancy), is encoded by the env gene of ERVWE1, a replication-incompetent HERV-W element located on human chromosome 7q21-22 [7,18] that has inactivating mutations in the gag and pol genes and is not able to form virus-like particles. In human DNA, there are multiple copies of HERV-W elements; numbers can vary [19][20], but there are about 70 gag, 100 pro, and 30 env HERV-Wrelated regions [21][22]; the family is retrotransposably active [12] and generates new recombinant copies in cancer cells [23].…”

“…Syncytin-1 originates from the ERVWE1 element on chromosome 7; the origin of MSRV is still debated [16]. Sequencing of virionic MSRV genomes identified a putative 7,630-nucleotide-long reconstituted retroviral organization with RU5, gag, pol, env, and U3R regions [16]. These sequences belong to the HERV-W family [18], classified in (simple) Gammaretroviruses [13].…”

“…Increasing evidence shows links of HERVs with some human diseases, such as male infertility, schizophrenia, and cancer [6,[10][11]16]. Several studies reported expression of one or more HERVs in physiological or pathological conditions, in one or more body sites.…”