Association of human endogenous retroviruses with multiple sclerosis and possible interactions with herpes viruses

Abstract

The hypothesis that human endogenous retroviruses (HERVs) play a role in autoimmune diseases is subject to increasing attention. HERVs represent both putative susceptibility genes and putative pathogenic viruses in the immune-mediated neurological disease multiple sclerosis (MS). Gammaretroviral HERV sequences are found in reverse transcriptase-positive virions produced by cultured mononuclear cells from MS patients, and they have been isolated from MS samples of plasma, serum and CSF, and characterised to some extent at the nucleotide, protein/enzyme, virion and immunogenic level. Two types of sequences, HERV-H and HERV-W, have been reported. No known HERV-H or HERV-W copy contains complete ORFs in all prerequisite genes, although several copies have coding potential, and several such sequences are specifically activated in MS, apparently resulting in the production of complete, competent virions. Increased antibody reactivity to specific Gammaretroviral HERV epitopes is found in MS serum and CSF, and cell-mediated immune responses have also been reported. Further, HERV-encoded proteins can have neuropathogenic effects. The activating factor(s) in the process resulting in protein or virion production may be members of the Herpesviridae. Several herpes viruses, such as HSV-1, VZV, EBV and HHV-6, have been associated with MS pathogenesis, and retroviruses and herpes viruses have complex interactions. The current understanding of HERVs, and specifically the investigations of HERV activation and expression in MS are the major subjects of this review, which also proposes to synergise the herpes and HERV findings, and presents several possible pathogenic mechanisms for HERVs in MS.

Pseudotyping of Porcine Endogenous Retrovirus by Xenotropic Murine Leukemia Virus in a Pig Islet Xenotransplantation Model

“…There is only one study suggesting that PERV virions do not efficiently package human endogenous retrovirus sequences (48). Thus, there is a possibility that PERV could be pseudotyped in human patients by complementation with human endogenous retrovirus envelope sequences encoded by human endogenous retrovirus (HERV-W) (49,50), HERV-E (51) or HERV-K (52) and expressed as functional proteins in different human tissues. Whether the same could occur by exogenous retroviruses such as HIV and HTLV is still an open question.…”

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).…”

Could Multiple Sclerosis Develop due to Epstein Barr Virus Infections Causing a Time-Delayed Transcriptional-Activation of Human Endogenous Retroviruses?

“…Retroviruses are also able to enter an integrated latent stage and have earlier been proposed to be involved in MS [14][15][16]. Indeed, towards 8% of our genomic DNA consists of DNA of retroviral origin [17] How would it be possible that an initial EBV infection, low-level latent EBV expression or defective silencing of integrated EBVs, subsequently could lead to a time-delayed expression of HERVs?…”