Contributions
Abstract: P1635
Type: LB Poster
Abstract Category: Late Breaking News
Introduction: Human Endogenous Retrovirus (HERV) is derived from ancestral infections and comprises around 8% of the human genome. HERV-W may play a role in MS pathogenesis since HERV-W protein can be detected in MS plaques and high levels and frequency of provirus expression occurs in MS patients. Nevertheless, little is known regarding to the source of the HERV-W transcripts in MS patients. Herein, we performed a transcriptome of MS patients to identify the most active HERV-W loci.
Methods: Five PBMC samples from MS patients under relapsing conditions with EDSS< 3 and treating with bInterferon and five samples from healthy subjects were submitted to RNAseq in illumina HiSeq. Reads were mapped to human genome (hg19) with Star alignment software, normalized and inspected for differential expression with DeSeq2. In parallel, 10 additional PBMC from MS patients (5 with EDSS>6 and 5 with EDSS< 3) and 5 healthy controls had the HERV-W envelope gene amplified and sequenced in Ion torrent platform. Reads were mapped to HERV-W reference loci and the number of transcripts of each provirus was determined. The relative expression of HERV-W was also determined through Real Time PCR.
Results and discussion: MS patients presented 4-fold higher levels of HERV-W expression than healthy subjects, in agreement to previous studies. Transcriptome data revealed that about 30 HERV-W loci were differently expressed, and of those 15 were upregulated in MS patients. The most active loci were 1p22.2, 3q23, 5p14.3, 7q21.2(ERVW-1), 13q13.3, Xp11.2 and Xq21.1. Amplicon sequencing confirmed the most active loci found in transcriptome experiment and also revealed that patients with higher EDSS (>6) presented higher number of active loci compared to health individuals (p=0.01), suggesting that MS patients with higher disability present distinct profile of HERV-W expression.
Conclusion: To our knowledge, this is the first report of HERV-W transcriptome in MS patients. HERV-W most active loci and proviruses differentially expressed were identified. In addition, MS patients with high EDSS seems to present higher diversity of HERV-W transcripts.
Disclosure: Nali LH: nothing to disclose
Silva IT: nothing to disclose
Olival GS: nothing to disclose
Dias-Neto: nothing to disclose
Silva DF: nothing to disclose
Urbano PR: nothing to disclose
Penalva-de-Oliveira AC: nothing to disclose
Romano: Nothing to disclose
Funding: Fundação de Amparo a Pesquisa do Estado de São Paulo (FAPESP): grant# 2015/05958-3 and grant#2013/24223-9
Abstract: P1635
Type: LB Poster
Abstract Category: Late Breaking News
Introduction: Human Endogenous Retrovirus (HERV) is derived from ancestral infections and comprises around 8% of the human genome. HERV-W may play a role in MS pathogenesis since HERV-W protein can be detected in MS plaques and high levels and frequency of provirus expression occurs in MS patients. Nevertheless, little is known regarding to the source of the HERV-W transcripts in MS patients. Herein, we performed a transcriptome of MS patients to identify the most active HERV-W loci.
Methods: Five PBMC samples from MS patients under relapsing conditions with EDSS< 3 and treating with bInterferon and five samples from healthy subjects were submitted to RNAseq in illumina HiSeq. Reads were mapped to human genome (hg19) with Star alignment software, normalized and inspected for differential expression with DeSeq2. In parallel, 10 additional PBMC from MS patients (5 with EDSS>6 and 5 with EDSS< 3) and 5 healthy controls had the HERV-W envelope gene amplified and sequenced in Ion torrent platform. Reads were mapped to HERV-W reference loci and the number of transcripts of each provirus was determined. The relative expression of HERV-W was also determined through Real Time PCR.
Results and discussion: MS patients presented 4-fold higher levels of HERV-W expression than healthy subjects, in agreement to previous studies. Transcriptome data revealed that about 30 HERV-W loci were differently expressed, and of those 15 were upregulated in MS patients. The most active loci were 1p22.2, 3q23, 5p14.3, 7q21.2(ERVW-1), 13q13.3, Xp11.2 and Xq21.1. Amplicon sequencing confirmed the most active loci found in transcriptome experiment and also revealed that patients with higher EDSS (>6) presented higher number of active loci compared to health individuals (p=0.01), suggesting that MS patients with higher disability present distinct profile of HERV-W expression.
Conclusion: To our knowledge, this is the first report of HERV-W transcriptome in MS patients. HERV-W most active loci and proviruses differentially expressed were identified. In addition, MS patients with high EDSS seems to present higher diversity of HERV-W transcripts.
Disclosure: Nali LH: nothing to disclose
Silva IT: nothing to disclose
Olival GS: nothing to disclose
Dias-Neto: nothing to disclose
Silva DF: nothing to disclose
Urbano PR: nothing to disclose
Penalva-de-Oliveira AC: nothing to disclose
Romano: Nothing to disclose
Funding: Fundação de Amparo a Pesquisa do Estado de São Paulo (FAPESP): grant# 2015/05958-3 and grant#2013/24223-9