Absence of serological evidence for foamy virus infection in patients with amyotrophic lateral sclerosis

Rösener, Martin; Hahn, Heidi; Kranz, Manuela; Heeney, Jonathan L.; Rethwilm, Axel

doi:10.1002/(sici)1096-9071(199603)48:3<222::aid-jmv2>3.0.co;2-a

Cited by 23 publications

(2 citation statements)

References 37 publications

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“…The failure to detect oncovirus sequences is consistent with our previous observations concerning the absence of HTLV tax-rex in such cases [Andrews et al, 1997]. Similarly, the absence of foamy virus sequences is in agreement with the findings of Rosener et al [1996].…”

Section: Discussionsupporting

confidence: 92%

Detection of reverse transcriptase activity in the serum of patients with motor neurone disease

et al. 2000

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The recognition that both human and murine retroviruses can cause motor neurone disease-like syndromes has raised the possibility that a retrovirus may be involved in the aetiology of motor neurone disease. This possibility was explored by looking for evidence of reverse transcriptase in the serum of motor neurone disease patients. Sera from 56 patients with motor neurone disease and 58 controls were tested by the product-enhanced reverse transcriptase assay, a technique that is approximately a million fold more sensitive than conventional reverse transcriptase assays and capable of detecting very low numbers of retroviral particles. Cell-free reverse transcriptase activity was detected in the serum of 33 of the 56 motor neurone disease patients (59%) but in only 3 of the controls (P < 0.00001). The reverse transcriptase activity was detectable in the presence of a large excess of an effective inhibitor of human cellular DNA polymerases and was therefore tentatively considered to be compatible with a retroviral origin. The reverse transcriptase activity, however, was not found to be due to the presence of known human exogenous retroviruses including HIV-1, HIV-2, HTLV-I, HTLV-II, HRV-5 or human foamy virus, as assessed by PCR-based assays. Further investigations will be required to determine the source of the reverse transcriptase activity observed in these motor neurone disease patient sera.

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Section: Discussionsupporting

confidence: 92%

Detection of reverse transcriptase activity in the serum of patients with motor neurone disease

et al. 2000

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“…These are non-human viruses but human infections have been described. Antibodies to this virus were described in 25–45% of patients with ALS in a series of publications from a single laboratory [ 100 – 102 ]; however it could not be replicated by another group in which they examined serum and CSF samples from only eight patients with ALS [ 103 ].…”

Section: Association Of Exogenous Retroviruses With Als-like Syndromesmentioning

confidence: 99%

Retroviral Elements in Pathophysiology and as Therapeutic Targets for Amyotrophic Lateral Sclerosis

Pandya

Pasternack

et al. 2022

Neurotherapeutics

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The study of the role of retroviruses in amyotrophic lateral sclerosis (ALS) dates back to the 1960s shortly after transposable elements themselves were first discovered. It was quickly realized that in wild mice both horizontal and vertical transmissions of retroviral elements were key to the development of an ALS-like syndrome leading to the postulate that endogenous retroviruses (ERVs) contribute significantly to the pathogenicity of this disease. Subsequent studies identified retroviral reverse transcriptase activity in brains of individuals with ALS from Guam. However, except for a single study from the former Soviet Union, ALS could not be transmitted to rhesus macaques. The discovery of an ALS-like syndrome in human immunodeficiency virus (HIV) and human T cell leukemia virus infected individuals led to renewed interest in the field and reverse transcriptase activity was found in the blood and cerebrospinal fluid of individuals with sporadic ALS. However, exogenous retroviruses could not be found in individuals with ALS which further reinforced the possibility of involvement of a human ERV (HERV). The first demonstration of the involvement of a HERV was the discovery of the activation of human endogenous retrovirus-K subtype HML-2 in the brains of individuals with ALS. The envelope protein of HML-2 is neurotoxic and transgenic animals expressing the envelope protein develop an ALS-like syndrome. Activation of HML-2 occurs in the context of generalized transposable element activation and is not specific for ALS. Individuals with HIV-associated ALS show a remarkable response to antiretroviral therapy; however, antiretroviral trials in ALS down-regulate HML-2 without ameliorating the disease. This highlights the need for specific drugs to be developed against HML-2 as a novel therapeutic target for ALS. Other approaches might include antisense oligonucleotides, shRNA targeted against the envelope gene or antibodies that can target the extracellular envelope protein. Future clinical trials in ALS should consider combination therapies to control these ERVs.

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Retroviruses and Associated Diseases in Humans

Dezzutti

Heneine

Boneva

et al. 2010

Topley &Amp; Wilson's Microbiology and Microbial Infections

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Absence of serological evidence for foamy virus infection in patients with amyotrophic lateral sclerosis

Cited by 23 publications

References 37 publications

Detection of reverse transcriptase activity in the serum of patients with motor neurone disease

Detection of reverse transcriptase activity in the serum of patients with motor neurone disease

Retroviral Elements in Pathophysiology and as Therapeutic Targets for Amyotrophic Lateral Sclerosis

Retroviruses and Associated Diseases in Humans

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