B–lymphoblastoid cell lines from multiple sclerosis patients and a healthy control producing a putative new human retrovirus and Epstein–Barr virus

Munch, Mette; Møller-Larsen, Anné; Christensen, Tove; Morling, Niels; Hansen, Hans J.; Haahr, S

doi:10.1177/135245859500100204

Cited by 41 publications

(31 citation statements)

References 22 publications

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“…Although EBV is not detected in the brain of MS patients, the implication of EBV in MS is supported by in vitro findings of viral expression or sequences. In contrast to healthy seropositive controls, B cells from MS patients have a tendency to transform spontaneously [61,62]. This may indicate an altered regulation of EBV transcription, and potentially involve endogenous retroviruses [63], which were also found in these cell lines [64].…”

Section: Detection Of Virus In Bloodmentioning

confidence: 96%

Multiple sclerosis is linked to Epstein‐Barr virus infection

Haahr

Höllsberg

2006

Reviews in Medical Virology

111

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The aetiology and pathogenesis of MS are unknown, but environmental agents, genetic susceptibility and stochastic events are likely to be involved. In order to evaluate the possibility that MS is linked to EBV infection, we here evaluate studies on MS- and EBV-epidemiology, prospective and retrospective analysis of EBV-serology, investigations of EBV DNA sequences in blood and tissues, specificity of antibodies in oligoclonal bands in MS patients and results from antiviral chemotherapy of MS patients. It could be demonstrated that EBV is complying with the epidemiological observations in MS and that all MS patients are seropositive to EBV in contrast to healthy controls. Importantly, despite difficulties in diagnosing child-MS, the vast majority of these patients are also EBV seropositive. In contrast to control groups, recent EBV infections have never been observed in children or adults with MS. Further prospective studies indicate a 2.8 times higher tendency for development of MS after infectious mononucleosis. In MS patients, unbiased analyses pull out EBV antigens as high-affinity targets for the antibodies in the oligoclonal bands. Humans are the exclusive natural host for EBV, a finding that may explain why MS is unique to humans. Together these unique observations strongly suggest a linkage between MS and EBV infection. Infection by EBV offers numerable mechanisms to perturb the immune system, including mimicry and superantigen induction, which may potentially participate in the disease mechanisms. In contrast, studies demonstrating higher IgG titres and occurrence of viral DNA in serum/plasma are likely to reflect a consequence of the disease. An explanation for a potential role of respiratory diseases in MS is discussed. It is concluded that the ultimate test to the hypothesis of MS and EBV is the development and application of an EBV vaccine, which is predicted to eradicate the disease.

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Section: Detection Of Virus In Bloodmentioning

confidence: 96%

Multiple sclerosis is linked to Epstein‐Barr virus infection

Haahr

Höllsberg

2006

Reviews in Medical Virology

111

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“…EMs on these cultures show RVLPs, and RT assays on purified viral material from these cultures are positive. As illustrated in Figure 5, the extracellular RVLPs are commonly associated with the outer cell membrane, vary in size from 70 to 100 nm in size (like HTLV-1/-2, which also differ widely in size [86,121]), and appear morphologically similar to type C retroviruses in being irregularly rounded, with surface projections on the envelope, and with a relatively electron-dense nucleocapsid/core [120,[122][123][124]. Such cultures were established from 5 of 21 consecutive MS patients and from 1 of 13 consecutive Figure 3.…”

Section: Cell Culturesmentioning

confidence: 99%

“…ASLV, avian sarcoma-leukosis virus; BaEV, baboon endogenous retrovirus; HML, human MMTV-like; HSRV, human spuma retrovirus; IAP, intracisternal particle (m: from mouse, ha: from hamster); JSRV, Jaagsiekte sheep retrovirus; MLV, murine leukaemia virus; MPMV, Mason-Pfizer monkey virus; MMTV, mouse mammary tumour virus; RERV-H, rabbit endogenous retrovirus; WDSV, walleye dermal sarcoma virus 186 186 T. Christensen T. Christensen healthy controls [124 and references therein]. The cultures also express EBV encoded proteins and occasionally EBV virions, and were initially classified (and published) as B-lymphoblastoid cell lines, for example [122][123][124]. However, the cultures are not clonal in origin, and, while containing a majority of B cells, also maintain a dynamic population equilibrium with from 5% to 15% CD3þ, CD4À, CD8À T cells [125].…”

Section: Cell Culturesmentioning

confidence: 99%

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

2005

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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.

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“…Similarly, retrovirus-like particles (RVLP) have been found in body fluids from patients with rheumatoid arthritis (RA) (469), SLE (480), and epidemic neuropathy (418) and in cell cultures established from individuals with testicular tumors (46,71) and chronic fatigue syndrome (192). In addition, RVLPs have also been observed in healthy human tissues and fluids including placenta (241,504) and breast milk (138,338) and in cultured cells (126,328,348). Although reported as being retroviruses, such particles do not always have the expected morphology or size of retroviruses; for example, particles described in RA (469) have an apparent diameter of 200 nm, which is roughly double that expected for retroviruses, and their identity as such is therefore doubtful.…”

Section: Electron Microscopymentioning

confidence: 99%

“…A second retrovirus associated with MS was also first detected as extracellular RVLPs and RT activity in mitogen-stimulated T and B lymphocytes from MS patients and healthy individuals (96,99,194,348,456). Subsequently, RT-PCR with primer sets specific for several different HERV families was employed to identify the viral genome encoding these purified RVLPs.…”

Section: Herv-h(rgh-2)mentioning

confidence: 99%

Human RNA “Rumor” Viruses: the Search for Novel Human Retroviruses in Chronic Disease

Voisset

Weiss

Griffiths

2008

Microbiol Mol Biol Rev

143

156

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SUMMARY Retroviruses are an important group of pathogens that cause a variety of diseases in humans and animals. Four human retroviruses are currently known, including human immunodeficiency virus type 1, which causes AIDS, and human T-lymphotropic virus type 1, which causes cancer and inflammatory disease. For many years, there have been sporadic reports of additional human retroviral infections, particularly in cancer and other chronic diseases. Unfortunately, many of these putative viruses remain unproven and controversial, and some retrovirologists have dismissed them as merely “human rumor viruses.” Work in this field was last reviewed in depth in 1984, and since then, the molecular techniques available for identifying and characterizing retroviruses have improved enormously in sensitivity. The advent of PCR in particular has dramatically enhanced our ability to detect novel viral sequences in human tissues. However, DNA amplification techniques have also increased the potential for false-positive detection due to contamination. In addition, the presence of many families of human endogenous retroviruses (HERVs) within our DNA can obstruct attempts to identify and validate novel human retroviruses. Here, we aim to bring together the data on “novel” retroviral infections in humans by critically examining the evidence for those putative viruses that have been linked with disease and the likelihood that they represent genuine human infections. We provide a background to the field and a discussion of potential confounding factors along with some technical guidelines. In addition, some of the difficulties associated with obtaining formal proof of causation for common or ubiquitous agents such as HERVs are discussed.

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B–lymphoblastoid cell lines from multiple sclerosis patients and a healthy control producing a putative new human retrovirus and Epstein–Barr virus

Cited by 41 publications

References 22 publications

Multiple sclerosis is linked to Epstein‐Barr virus infection

Multiple sclerosis is linked to Epstein‐Barr virus infection

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

Human RNA “Rumor” Viruses: the Search for Novel Human Retroviruses in Chronic Disease

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