Blood virome research in myalgic encephalomyelitis/chronic fatigue syndrome: challenges and opportunities

Abstract:

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a debilitating disease with a complex clinical presentation and an unknown etiology. Various viral infections have been proposed as potential triggers of ME/CFS onset, but no specific pathogen has been identified in all cases of postinfectious ME/CFS.

The symptomatology of the postacute sequelae of SARS-CoV-2, or long COVID, mirrors that of ME/CFS, with nearly half of long COVID patients meeting ME/CFS diagnostic criteria. The influx of newly diagnosed patients has reinvigorated interest in ME/CFS pathogenesis research, with an emphasis on viral triggers.

This review summarizes the current understanding of ME/CFS research on viral triggers, including blood virome screening studies. To further elucidate the molecular basis of ME/CFS, there is a need to develop innovative bioinformatics tools capable of analyzing complex virome data and integrating multiomics information.

Source: Obraitis D, Li D. Blood virome research in myalgic encephalomyelitis/chronic fatigue syndrome: challenges and opportunities. Curr Opin Virol. 2024 Nov 12:101437. doi: 10.1016/j.coviro.2024.101437. Epub ahead of print. PMID: 39537445. https://www.sciencedirect.com/science/article/pii/S1879625724000518 (Full text)

Investigating the Human Intestinal DNA Virome and Predicting Disease-Associated Virus-Host Interactions in Severe Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)

Abstract:

Understanding how the human virome, and which of its constituents, contributes to health or disease states is reliant on obtaining comprehensive virome profiles. By combining DNA viromes from isolated virus-like particles (VLPs) and whole metagenomes from the same faecal sample of a small cohort of healthy individuals and patients with severe myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), we have obtained a more inclusive profile of the human intestinal DNA virome.

Key features are the identification of a core virome comprising tailed phages of the class Caudoviricetes, and a greater diversity of DNA viruses including extracellular phages and integrated prophages. Using an in silico approach, we predicted interactions between members of the Anaerotruncus genus and unique viruses present in ME/CFS microbiomes. This study therefore provides a framework and rationale for studies of larger cohorts of patients to further investigate disease-associated interactions between the intestinal virome and the bacteriome.

Source: Hsieh SY, Savva GM, Telatin A, Tiwari SK, Tariq MA, Newberry F, Seton KA, Booth C, Bansal AS, Wileman T, Adriaenssens EM, Carding SR. Investigating the Human Intestinal DNA Virome and Predicting Disease-Associated Virus-Host Interactions in Severe Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS). Int J Mol Sci. 2023 Dec 8;24(24):17267. doi: 10.3390/ijms242417267. PMID: 38139096. https://www.mdpi.com/1422-0067/24/24/17267 (Full text)

A multicenter virome analysis of blood, feces, and saliva in myalgic encephalomyelitis/chronic fatigue syndrome

Abstract:

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is estimated to affect 0.4%-2.5% of the global population. Most cases are unexplained; however, some patients describe an antecedent viral infection or response to antiviral medications.

We report here a multicenter study for the presence of viral nucleic acid in blood, feces, and saliva of patients with ME/CFS using polymerase chain reaction and high-throughput sequencing.

We found no consistent group-specific differences other than a lower prevalence of anelloviruses in cases compared to healthy controls. Our findings suggest that future investigations into viral infections in ME/CFS should focus on adaptive immune responses rather than surveillance for viral gene products.

Source: Briese T, Tokarz R, Bateman L, Che X, Guo C, Jain K, Kapoor V, Levine S, Hornig M, Oleynik A, Quan PL, Wong WH, Williams BL, Vernon SD, Klimas NG, Peterson DL, Montoya JG, Ian Lipkin W. A multicenter virome analysis of blood, feces, and saliva in myalgic encephalomyelitis/chronic fatigue syndrome. J Med Virol. 2023 Aug;95(8):e28993. doi: 10.1002/jmv.28993. PMID: 37526404. https://pubmed.ncbi.nlm.nih.gov/37526404/ 

Does the microbiome and virome contribute to myalgic encephalomyelitis/chronic fatigue syndrome?

Abstract:

Myalgic encephalomyelitis (ME)/chronic fatigue syndrome (CFS) (ME/CFS) is a disabling and debilitating disease of unknown aetiology. It is a heterogeneous disease characterized by various inflammatory, immune, viral, neurological and endocrine symptoms. Several microbiome studies have described alterations in the bacterial component of the microbiome (dysbiosis) consistent with a possible role in disease development. However, in focusing on the bacterial components of the microbiome, these studies have neglected the viral constituent known as the virome.

Viruses, particularly those infecting bacteria (bacteriophages), have the potential to alter the function and structure of the microbiome via gene transfer and host lysis. Viral-induced microbiome changes can directly and indirectly influence host health and disease. The contribution of viruses towards disease pathogenesis is therefore an important area for research in ME/CFS.

Recent advancements in sequencing technology and bioinformatics now allow more comprehensive and inclusive investigations of human microbiomes. However, as the number of microbiome studies increases, the need for greater consistency in study design and analysis also increases. Comparisons between different ME/CFS microbiome studies are difficult because of differences in patient selection and diagnosis criteria, sample processing, genome sequencing and downstream bioinformatics analysis. It is therefore important that microbiome studies adopt robust, reproducible and consistent study design to enable more reliable and valid comparisons and conclusions to be made between studies. This article provides a comprehensive review of the current evidence supporting microbiome alterations in ME/CFS patients. Additionally, the pitfalls and challenges associated with microbiome studies are discussed.

Source: Newberry F, Hsieh SY, Wileman T, Carding SR. Does the microbiome and virome contribute to myalgic encephalomyelitis/chronic fatigue syndrome? Clin Sci (Lond). 2018 Mar 9;132(5):523-542. doi: 10.1042/CS20171330. Print 2018 Mar 15. https://www.ncbi.nlm.nih.gov/pubmed/29523751

A Role for the Intestinal Microbiota and Virome in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)?

Abstract:

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a heterogeneous disorder of significant societal impact that is proposed to involve both host and environmentally derived aetiologies that may be autoimmune in nature. Immune-related symptoms of at least moderate severity persisting for prolonged periods of time are common in ME/CFS patients and B cell depletion therapy is of significant therapeutic benefit. The origin of these symptoms and whether it is infectious or inflammatory in nature is not clear, with seeking evidence of acute or chronic virus infections contributing to the induction of autoimmune processes in ME/CFS being an area of recent interest.

This article provides a comprehensive review of the current evidence supporting an infectious aetiology for ME/CFS leading us to propose the novel concept that the intestinal microbiota and in particular members of the virome are a source of the “infectious” trigger of the disease. Such an approach has the potential to identify disease biomarkers and influence therapeutics, providing much-needed approaches in preventing and managing a disease desperately in need of confronting.

 

Source: Navaneetharaja N, Griffiths V, Wileman T, Carding SR. A Role for the Intestinal Microbiota and Virome in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)? J Clin Med. 2016 Jun 6;5(6). pii: E55. doi: 10.3390/jcm5060055. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4929410/ (Full article)