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Background <p>Viral infections may influence stroke pathophysiology. Several infections have been linked to increased risk of stroke, however our understanding of these viral interactions with immune and host tissue is limited. We performed a transcriptomic analysis of the blood virome following ischemic stroke to study these interactions.</p> Methods <p>Viruses were measured by RNA sequencing of blood from 37 patients with ischemic stroke and 32 matched controls. RNA reads are aligned against a human reference genome, as well as a comprehensive database of human virus genomes. Host gene expression following stroke is examined in relation to the presence of viral transcripts.</p> Results <p>Viral RNAs were detected in the blood samples of both ischemic stroke and control groups. Viral reads with a prevalence &gt; 3% and raw counts &gt; 2 were from a total of 6 viral families. This included several human herpesviruses (HHVs), adenoviruses, and papillomaviruses, as well as human pegivirus, respiratory syncytial virus, and human endogenous retrovirus K (HERV-K). Combined, counts from HHVs were higher in stroke compared to control by a fold change of 2.13. Coinfection with multiple HHVs was more common in stroke, with a 1.23 fold increase in the number of detected herpesviruses. Reads from two viral genes were increased in stroke, <i>UL95</i> from cytomegalovirus (CMV), and <i>EBNA2</i> from Epstein-Barr virus (EBV). Genes associated with stroke, including <i>APOE</i>, <i>C3</i>, <i>PDGF</i>, and <i>CXCL2</i> were differentially expressed in stroke samples which contained high counts of one or both of <i>UL95</i> and <i>EBNA2</i>.</p> Conclusion <p>Viral RNAs from multiple families can be detected within the human blood virome. HHV transcripts were the most abundant of viral RNAs detected. Among stroke patients, HHV transcripts were more prevalent, with higher counts, and indicated a higher rate of coinfection with multiple HHV species. Expression of the EBV gene <i>EBNA2</i> and the CMV gene <i>UL95</i> may relate to changes in immune gene expression following stroke. Further evaluation is needed to determine the effects that the human virome have on stroke risk, immune response to stroke, and long-term outcome.</p>

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Metagenomic analysis of blood virome in ischemic stroke reveals an increase in herpesvirus transcripts and host immune activation

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年7月10日

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  • Michael D. Clarke,
  • Sarina Falcione,
  • Roobina Boghozian,
  • Raluca Todoran,
  • Yiran Zhang,
  • Maria Guadalupe C. Real,
  • Alexis StPierre,
  • Twinkle Joy,
  • Glen C. Jickling

摘要

Background

Viral infections may influence stroke pathophysiology. Several infections have been linked to increased risk of stroke, however our understanding of these viral interactions with immune and host tissue is limited. We performed a transcriptomic analysis of the blood virome following ischemic stroke to study these interactions.

Methods

Viruses were measured by RNA sequencing of blood from 37 patients with ischemic stroke and 32 matched controls. RNA reads are aligned against a human reference genome, as well as a comprehensive database of human virus genomes. Host gene expression following stroke is examined in relation to the presence of viral transcripts.

Results

Viral RNAs were detected in the blood samples of both ischemic stroke and control groups. Viral reads with a prevalence > 3% and raw counts > 2 were from a total of 6 viral families. This included several human herpesviruses (HHVs), adenoviruses, and papillomaviruses, as well as human pegivirus, respiratory syncytial virus, and human endogenous retrovirus K (HERV-K). Combined, counts from HHVs were higher in stroke compared to control by a fold change of 2.13. Coinfection with multiple HHVs was more common in stroke, with a 1.23 fold increase in the number of detected herpesviruses. Reads from two viral genes were increased in stroke, UL95 from cytomegalovirus (CMV), and EBNA2 from Epstein-Barr virus (EBV). Genes associated with stroke, including APOE, C3, PDGF, and CXCL2 were differentially expressed in stroke samples which contained high counts of one or both of UL95 and EBNA2.

Conclusion

Viral RNAs from multiple families can be detected within the human blood virome. HHV transcripts were the most abundant of viral RNAs detected. Among stroke patients, HHV transcripts were more prevalent, with higher counts, and indicated a higher rate of coinfection with multiple HHV species. Expression of the EBV gene EBNA2 and the CMV gene UL95 may relate to changes in immune gene expression following stroke. Further evaluation is needed to determine the effects that the human virome have on stroke risk, immune response to stroke, and long-term outcome.