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Open Access 01-12-2019 | Amyotrophic Lateral Sclerosis | Letter to the Editor

Technical considerations in detection of HERV-K in amyotrophic lateral sclerosis: selection of controls and the perils of qPCR

Authors: Marta Garcia-Montojo, Wenxue Li, Avindra Nath

Published in: Acta Neuropathologica Communications | Issue 1/2019

Excerpt

The study by Garson et al. [12] failed to show a difference between the expression levels of Human endogenous retrovirus K (HERV-K) in amyotrophic lateral sclerosis (ALS) brain samples and controls by qPCR. However, several technical aspects need to be considered for the interpretation of their findings. Nearly half (11/23) the control samples had cancer. It is well known that HERV-K is activated in several types of cancer such as teratocarcinoma, germ cell tumors, melanoma, ovarian, and prostate cancer [4, 5, 14, 17, 23, 24, 34] and its expression is associated with various features of malignant cells [3, 25, 28, 30, 35]. Cancer cells can release viral-like particles containing viral products [3, 5, 23, 30]. These products would be expected to circulate within the brain vasculature and extracellular space hence can easily be detected in brain extracts. This is consistent with our observations where we were able to detect HERV-K transcripts in brain of patients with systemic cancer without any brain metastasis [6]. Garson et al., also found high levels of HERV-K transcripts in patients with cerebral infarcts. This is not surprising. Necrosis of the brain is likely to induce repair mechanisms that would include the presence of progenitor and stem cells. HERV-K and other endogenous retroviral elements are activated in these cells types and play an important role in cellular proliferation, similar to what is seen in cancer [11]. This raises two important questions: what the proper controls are to use in such studies and how does one reconcile the similarly opposite effects of HERV-K and other retroviral elements in cell proliferation and neurodegeneration. We have shown that HERV-K is specifically expressed in cortical neurons in a subpopulation of patients (~ 30%) with ALS [6, 21]. We did not see similar levels of activation in patients with other types of neurodegenerative disorders such as Alzheimer’s disease [21] and Parkinson’s disease [6]. Although other groups have shown the activation of other transposable elements in Alzheimer’s disease [13]. Similarly, increased circulating levels of antibodies directed against the HERV-K env have been found in serum and CSF of ALS patients [2]. …

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Title: Technical considerations in detection of HERV-K in amyotrophic lateral sclerosis: selection of controls and the perils of qPCR
Authors: Marta Garcia-Montojo
Wenxue Li
Avindra Nath
Publication date: 01-12-2019
Publisher: BioMed Central
Keywords: Amyotrophic Lateral Sclerosis
Parkinson's Disease
Published in: Acta Neuropathologica Communications / Issue 1/2019
Electronic ISSN: 2051-5960
DOI: https://doi.org/10.1186/s40478-019-0753-z

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Technical considerations in detection of HERV-K in amyotrophic lateral sclerosis: selection of controls and the perils of qPCR

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