{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T13:56:47Z","timestamp":1784037407937,"version":"3.55.0"},"reference-count":51,"publisher":"American Society for Clinical Investigation","issue":"11","license":[{"start":{"date-parts":[[2022,6,8]],"date-time":"2022-06-08T00:00:00Z","timestamp":1654646400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["R01 A1084898"],"award-info":[{"award-number":["R01 A1084898"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["P30 CA016058"],"award-info":[{"award-number":["P30 CA016058"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,6,8]]},"abstract":"<jats:p>\n                    Myalgic encephalomyelitis\/chronic fatigue syndrome (ME\/CFS) is a chronic, debilitating, multisystem illness of unknown etiology for which no cure and no diagnostic tests are available. Despite increasing evidence implicating EBV and human herpesvirus 6A (HHV-6A) as potential causative infectious agents in a subset of patients with ME\/CFS, few mechanistic studies address a causal relationship. In this study we examined a large ME\/CFS cohort and controls and demonstrated a significant increase in activin A and IL-21 serum levels, which correlated with seropositivity for antibodies against the EBV and HHV-6 protein deoxyuridine triphosphate nucleotidohydrolase (dUTPases) but no increase in CXCL13. These cytokines are critical for T follicular helper (T\n                    <jats:sub>FH<\/jats:sub>\n                    ) cell differentiation and for the generation of high-affinity antibodies and long-lived plasma cells. Notably, ME\/CFS serum was sufficient to drive T\n                    <jats:sub>FH<\/jats:sub>\n                    cell differentiation via an activin A\u2013dependent mechanism. The lack of simultaneous CXCL13 increase with IL-21 indicates impaired T\n                    <jats:sub>FH<\/jats:sub>\n                    function in ME\/CFS. In vitro studies revealed that virus dUTPases strongly induced activin A secretion while in vivo, EBV dUTPase induced the formation of splenic marginal zone B and invariant NKT\n                    <jats:sub>FH<\/jats:sub>\n                    cells. Together, our data indicate abnormal germinal center (GC) activity in participants with ME\/CFS and highlight a mechanism by which EBV and HHV6 dUTPases may alter GC and extrafollicular antibody responses.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.158193","type":"journal-article","created":{"date-parts":[[2022,4,28]],"date-time":"2022-04-28T12:01:34Z","timestamp":1651147294000},"source":"Crossref","is-referenced-by-count":33,"title":["EBV\/HHV-6A dUTPases contribute to myalgic encephalomyelitis\/chronic fatigue syndrome pathophysiology by enhancing TFH cell differentiation and extrafollicular activities"],"prefix":"10.1172","volume":"7","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6753-6211","authenticated-orcid":true,"given":"Brandon S.","family":"Cox","sequence":"first","affiliation":[{"name":"Department of Cancer Biology and 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