Quantitative analysis of human endogenous retrovirus-K transcripts in postmortem premotor cortex fails to confirm elevated expression of HERV-K RNA in amyotrophic lateral sclerosis
Abstract Over the past two decades a number of studies have demonstrated activity of the retroviral enzyme reverse transcriptase in the serum of patients with sporadic amyotrophic lateral sclerosis (ALS). Known human exogenous retroviruses such as HIV-1 have been eliminated as possible sources of th...
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| Format: | Article |
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BMC
2019-03-01
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| Series: | Acta Neuropathologica Communications |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s40478-019-0698-2 |
| _version_ | 1818199502073364480 |
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| author | Jeremy A. Garson Louise Usher Ammar Al-Chalabi Jim Huggett Edmund F. Day Adele L. McCormick |
| author_facet | Jeremy A. Garson Louise Usher Ammar Al-Chalabi Jim Huggett Edmund F. Day Adele L. McCormick |
| author_sort | Jeremy A. Garson |
| collection | DOAJ |
| description | Abstract Over the past two decades a number of studies have demonstrated activity of the retroviral enzyme reverse transcriptase in the serum of patients with sporadic amyotrophic lateral sclerosis (ALS). Known human exogenous retroviruses such as HIV-1 have been eliminated as possible sources of this activity and investigators have therefore considered the possibility that human endogenous retroviruses (HERVs) might be involved. HERV-K (HML-2) is the most recent retroviral candidate to be proposed following the observation of elevated HERV-K expression in cortical and spinal neurons of ALS patients and the demonstration of HERV-K envelope protein neurotoxicity in vitro and in transgenic mice. This retroviral hypothesis is an attractive one, not least because it raises the possibility that ALS might become treatable using antiretroviral drugs. In the present study we have attempted independent confirmation of the observation that HERV-K RNA levels are elevated in ALS brain. Total RNA was extracted from the postmortem premotor cortex of 34 patients with ALS and 23 controls. Quantitative real-time reverse transcription PCR (RT-qPCR) was performed according to the MIQE guidelines using HERV-K gag, pol and env primer sets. Data was analysed by the 2-∆∆Ct method with normalisation against two reference genes, GAPDH and XPNPEP1. Geometric mean HERV-K RNA expression levels in the premotor cortex of ALS patients were not found to be different from the expression levels in non-ALS controls. Our findings do not confirm the recently reported association between elevated cortical HERV-K RNA levels and ALS, and thus raise doubts about the role of this endogenous retrovirus in ALS pathogenesis. The results of this study may have implications for ongoing clinical trials aiming to suppress HERV-K activity with antiretroviral drugs. |
| first_indexed | 2024-12-12T02:22:47Z |
| format | Article |
| id | doaj.art-8a812992ed2e4731b65142f72d01d57d |
| institution | Directory Open Access Journal |
| issn | 2051-5960 |
| language | English |
| last_indexed | 2024-12-12T02:22:47Z |
| publishDate | 2019-03-01 |
| publisher | BMC |
| record_format | Article |
| series | Acta Neuropathologica Communications |
| spelling | doaj.art-8a812992ed2e4731b65142f72d01d57d2022-12-22T00:41:39ZengBMCActa Neuropathologica Communications2051-59602019-03-01711910.1186/s40478-019-0698-2Quantitative analysis of human endogenous retrovirus-K transcripts in postmortem premotor cortex fails to confirm elevated expression of HERV-K RNA in amyotrophic lateral sclerosisJeremy A. Garson0Louise Usher1Ammar Al-Chalabi2Jim Huggett3Edmund F. Day4Adele L. McCormick5Division of Infection and Immunity, University College LondonSchool of Life Sciences, University of WestminsterMaurice Wohl Clinical Neuroscience Institute, King’s College LondonMolecular and Cell Biology Team, LGCSchool of Life Sciences, University of WestminsterSchool of Life Sciences, University of WestminsterAbstract Over the past two decades a number of studies have demonstrated activity of the retroviral enzyme reverse transcriptase in the serum of patients with sporadic amyotrophic lateral sclerosis (ALS). Known human exogenous retroviruses such as HIV-1 have been eliminated as possible sources of this activity and investigators have therefore considered the possibility that human endogenous retroviruses (HERVs) might be involved. HERV-K (HML-2) is the most recent retroviral candidate to be proposed following the observation of elevated HERV-K expression in cortical and spinal neurons of ALS patients and the demonstration of HERV-K envelope protein neurotoxicity in vitro and in transgenic mice. This retroviral hypothesis is an attractive one, not least because it raises the possibility that ALS might become treatable using antiretroviral drugs. In the present study we have attempted independent confirmation of the observation that HERV-K RNA levels are elevated in ALS brain. Total RNA was extracted from the postmortem premotor cortex of 34 patients with ALS and 23 controls. Quantitative real-time reverse transcription PCR (RT-qPCR) was performed according to the MIQE guidelines using HERV-K gag, pol and env primer sets. Data was analysed by the 2-∆∆Ct method with normalisation against two reference genes, GAPDH and XPNPEP1. Geometric mean HERV-K RNA expression levels in the premotor cortex of ALS patients were not found to be different from the expression levels in non-ALS controls. Our findings do not confirm the recently reported association between elevated cortical HERV-K RNA levels and ALS, and thus raise doubts about the role of this endogenous retrovirus in ALS pathogenesis. The results of this study may have implications for ongoing clinical trials aiming to suppress HERV-K activity with antiretroviral drugs.http://link.springer.com/article/10.1186/s40478-019-0698-2Amyotrophic lateral sclerosisALSHuman endogenous retrovirusHERV-KHERV-WRNA |
| spellingShingle | Jeremy A. Garson Louise Usher Ammar Al-Chalabi Jim Huggett Edmund F. Day Adele L. McCormick Quantitative analysis of human endogenous retrovirus-K transcripts in postmortem premotor cortex fails to confirm elevated expression of HERV-K RNA in amyotrophic lateral sclerosis Acta Neuropathologica Communications Amyotrophic lateral sclerosis ALS Human endogenous retrovirus HERV-K HERV-W RNA |
| title | Quantitative analysis of human endogenous retrovirus-K transcripts in postmortem premotor cortex fails to confirm elevated expression of HERV-K RNA in amyotrophic lateral sclerosis |
| title_full | Quantitative analysis of human endogenous retrovirus-K transcripts in postmortem premotor cortex fails to confirm elevated expression of HERV-K RNA in amyotrophic lateral sclerosis |
| title_fullStr | Quantitative analysis of human endogenous retrovirus-K transcripts in postmortem premotor cortex fails to confirm elevated expression of HERV-K RNA in amyotrophic lateral sclerosis |
| title_full_unstemmed | Quantitative analysis of human endogenous retrovirus-K transcripts in postmortem premotor cortex fails to confirm elevated expression of HERV-K RNA in amyotrophic lateral sclerosis |
| title_short | Quantitative analysis of human endogenous retrovirus-K transcripts in postmortem premotor cortex fails to confirm elevated expression of HERV-K RNA in amyotrophic lateral sclerosis |
| title_sort | quantitative analysis of human endogenous retrovirus k transcripts in postmortem premotor cortex fails to confirm elevated expression of herv k rna in amyotrophic lateral sclerosis |
| topic | Amyotrophic lateral sclerosis ALS Human endogenous retrovirus HERV-K HERV-W RNA |
| url | http://link.springer.com/article/10.1186/s40478-019-0698-2 |
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