An alternative approach to medical genetics based on modern evolutionary                biology. Part 3: HERVs in diseases

Ryan, Frank

doi:10.1258/jrsm.2009.090221

Cited by 10 publications

(13 citation statements)

References 56 publications

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“…Among environmental factors, viral infections are most often linked to the etiology of MS (23,24). Predominantly, human herpesviruses (type 6A and -B [HHV-6A and -B]), varicella-zoster virus (VZV), Epstein-Barr virus (EBV), and human endogenous retroviruses (HERVs) are implicated as etiologic agents in MS (7,12,54,56,58). The concept that retroviruses contribute to MS originated in the realization that demyelinating diseases in animals were caused by such viruses (20,47).…”

mentioning

confidence: 99%

Expression of HERV-Fc1, a Human Endogenous Retrovirus, Is Increased in Patients with Active Multiple Sclerosis

Laska

Brudek

Nissen

et al. 2012

J Virol

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Multiple sclerosis (MS) is considered to be an autoimmune disease with an unknown cause and with immune system dysregulation. Among environmental factors, viruses are most often connected with the etiology of MS. Human endogenous retroviruses (HERVs) constitute 5 to 8% of human genomic DNA and have been detected as transcripts and proteins in the central nervous system (CNS) and peripheral blood, frequently in the context of neuroinflammation. HERV-Fc1, which belongs to the HERV-H/F family, has received our attention largely because of the genetic association with MS. We studied the expression of a capsid (Gag) protein of HERV-H/F origin by flow cytometry in peripheral blood mononuclear cells (PBMCs) from healthy controls and from MS patients with nonactive or active disease. There was a significant increase in HERV-H/F Gag expression in CD4 ؉ (P < 0.001) and CD8 ؉ (P < 0.001) T lymphocytes and in monocytes (P ‫؍‬ 0.0356) in PBMCs from MS patients with active disease. Furthermore, we have undertaken the first rigorous SYBR green-based absolute quantitative PCR (Q-PCR) evaluation approach to quantify extracellular HERV-Fc1 RNA viral loads in plasma from MS patients and healthy controls. We found a 4-fold increase in extracellular HERV-Fc1 RNA titers in patients with active MS compared with healthy controls (P < 0.001). These findings strengthen the link between HERV-Fc1 and the pathology of MS. The cause and biological consequences of these differential expression levels will be the subject of further investigation. HERV-Fc1 biology could be a compelling area for understanding the pathology of MS and possibly other autoimmune disorders.

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confidence: 99%

Expression of HERV-Fc1, a Human Endogenous Retrovirus, Is Increased in Patients with Active Multiple Sclerosis

Laska

Brudek

Nissen

et al. 2012

J Virol

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“…10,11 Growing evidence suggests that ERVs have significantly contributed to human evolution, development, and physiology; in addition, they play a role in the pathogenesis of human diseases. 12,13 Several endogenous retroviral envelope genes encode envelope glycoproteins, which have retained some characteristics of the cognate proteins produced by their ancestral infectious viruses, such as the ability to attach to a cell receptor, with crucial physiological consequences for the tissues in which they are expressed. 14 For example, six retroviral env genes containing an ORF are transcribed in the placenta: HERV-K, HERV-R(b), and ERV-T at low levels and HERV-R, HERV-W, and HERV-FRD at high levels.…”

Section: Introductionmentioning

confidence: 99%

Short Communication: Expression Profiles of Endogenous Retroviral Envelopes inMacaca mulatta(Rhesus Monkey)

Cha

Imai

et al. 2014

AIDS Research and Human Retroviruses

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Endogenous retroviruses (ERVs), which are footprints of ancient germline infections, were inserted into the genome during the early stages of primate evolution. Human endogenous retroviruses (HERVs) occupy approximately 8% of the human genome. Although most ERV genes are defective, with large deletions, stop codons, and frameshifts in their open reading frames (ORFs), some full-length sequences containing long ORFs are expressed in several tissues and cancers. Several envelope glycoproteins that are encoded by env genes have retained some characteristics of their ancestral infectious viruses. These glycoproteins play essential physiological roles in the organs in which they are expressed. Previous studies have demonstrated the expression of ERV env at the mRNA level in cells and tissues rather than at the protein level, which is more difficult to detect. However, it is not known whether Env is functionally conserved in primates. To understand the possible role of Env in primates, we examined the expression of the env genes of four ERVs (ERV-R, -K, -W, and -FRD) at the protein as well as mRNA levels in various tissues of the rhesus monkey. The ERV env gene products were observed at moderate to high levels in each tissue that was examined and showed tissue-specific expression patterns. Our data suggest a biologically important role for retroviral proteins in healthy tissues of the rhesus monkey.

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“…Useful, but inconclusive, information has come from the study of Mendelian genetics [1, 2], meanwhile, although the aetiology of MS remains uncertain, the innate and adaptive inflammatory processes involved are becoming increasingly understood at cellular and molecular level [3, 4]. There is evidence of genetic contribution to the autoimmune diseases.…”

Section: Introductionmentioning

confidence: 99%

“…Multiple sclerosis, or MS, has many of the features of an autoimmune disease, where the pathology involves an immune reaction to the body’s own cells or tissues – or to put it another way the failure of the adaptive immune system to recognise self. Useful, but inconclusive, information has come from the study of Mendelian genetics [ 1 , 2 ], meanwhile, although the aetiology of MS remains uncertain, the innate and adaptive inflammatory processes involved are becoming increasingly understood at cellular and molecular level [ 3 , 4 ]. There is evidence of genetic contribution to the autoimmune diseases.…”

Section: Introductionmentioning

confidence: 99%

“…The human extended Major Histocompatibility Complex, or xMHC, is a key genetic region with regard to the evolution, and expression, of our adaptive immunity, with 22% of its 421 genes believed to have immunoregulatory function, and various genes associated with auto-immunity [ 5 ]. There is also growing evidence that human endogenous retroviruses, or HERVs, have played an important role in the evolution of the xMHC, and it is likely that they continue to play an important role in its function and malfunction [ 1 , 6 , 7 ]. In addition we now know that HERVs and related genetic sequences have contributed to the evolution and structure of the human genome per se , with implications for human embryology and physiology [ 8 ].…”

Section: Introductionmentioning

confidence: 99%

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Human Endogenous Retroviruses in Multiple Sclerosis: Potential for Novel Neuro-Pharmacological Research

Fp¹

2011

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There is growing evidence that the env genes of two or more human endogenous retroviruses (HERVs) of the W family are contributing to the inflammatory processes, and thus to the pathogenesis, of multiple sclerosis (MS). Increasing understanding of the human endogenous retroviral locus, ERVWE1, and the putative multiple sclerosis associated retrovirus, or MSRV, and in particular of the HERV-W env sequences associated with these, offers the potential of new lines of pharmacological research that might assist diagnosis, prognosis and therapy of multiple sclerosis.

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An alternative approach to medical genetics based on modern evolutionary biology. Part 3: HERVs in diseases

Cited by 10 publications

References 56 publications

Expression of HERV-Fc1, a Human Endogenous Retrovirus, Is Increased in Patients with Active Multiple Sclerosis

Expression of HERV-Fc1, a Human Endogenous Retrovirus, Is Increased in Patients with Active Multiple Sclerosis

Short Communication: Expression Profiles of Endogenous Retroviral Envelopes inMacaca mulatta(Rhesus Monkey)

Human Endogenous Retroviruses in Multiple Sclerosis: Potential for Novel Neuro-Pharmacological Research

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