{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T07:19:50Z","timestamp":1775027990286,"version":"3.50.1"},"reference-count":41,"publisher":"Oxford University Press (OUP)","issue":"12","license":[{"start":{"date-parts":[[2013,6,1]],"date-time":"2013-06-01T00:00:00Z","timestamp":1370044800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2013,6,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Viruses enter into complex interactions within human hosts, leading to facilitation or suppression of each other\u2019s replication. Upon coinfection, GB virus C (GBV-C) suppresses HIV-1 replication in vivo and in vitro, and GBV-C coinfection is associated with prolonged survival in HIV-infected people. GBV-C is a lymphotropic virus capable of persistent infection. GBV-C infection is associated with reduced T cell activation in HIV-infected humans, and immune activation is a critical component of HIV disease pathogenesis. We demonstrate that serum GBV-C particles inhibited activation of primary human T cells. T cell activation inhibition was mediated by the envelope glycoprotein E2, because expression of E2 inhibited TCR-mediated activation of Lck. The region on the E2 protein was characterized and revealed a highly conserved peptide motif sufficient to inhibit TCR-mediated signaling. The E2 region contained a predicted Lck substrate site, and substitution of an alanine or histidine for the tyrosine reversed TCR-signaling inhibition. GBV-C E2 protein and a synthetic peptide representing the inhibitory amino acid sequence were phosphorylated by Lck in vitro. The synthetic peptide also inhibited TCR-mediated activation of primary human CD4+ and CD8+ T cells. Extracellular microvesicles from GBV-C E2\u2013expressing cells contained E2 protein and inhibited TCR signaling in bystander T cells not expressing E2. Thus, GBV-C reduced global T cell activation via competition between its envelope protein E2 and Lck following TCR engagement. This novel inhibitory mechanism of T cell activation may provide new approaches for HIV and immunoactivation therapy.<\/jats:p>","DOI":"10.4049\/jimmunol.1300589","type":"journal-article","created":{"date-parts":[[2013,5,18]],"date-time":"2013-05-18T04:37:56Z","timestamp":1368851876000},"page":"6351-6359","source":"Crossref","is-referenced-by-count":31,"title":["GB Virus C Particles Inhibit T Cell Activation via Envelope E2 Protein-Mediated Inhibition of TCR Signaling"],"prefix":"10.1093","volume":"190","author":[{"given":"Nirjal","family":"Bhattarai","sequence":"first","affiliation":[{"name":"Iowa City Veterans Affairs Medical Center , Iowa City, IA 52242"},{"name":"Interdisciplinary Program in Molecular and Cellular Biology, University of Iowa , Iowa City, IA 52242"},{"name":"Department of Internal Medicine, University of Iowa , Iowa City, IA 52242"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"James H","family":"McLinden","sequence":"additional","affiliation":[{"name":"Iowa City Veterans Affairs Medical Center , Iowa City, IA 52242"},{"name":"Department of Internal Medicine, University of Iowa , Iowa City, IA 52242"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jinhua","family":"Xiang","sequence":"additional","affiliation":[{"name":"Iowa City Veterans Affairs Medical Center , Iowa City, IA 52242"},{"name":"Department of Internal Medicine, University of Iowa , Iowa City, IA 52242"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alan L","family":"Landay","sequence":"additional","affiliation":[{"name":"Rush University Medical Center , Chicago, IL 60612"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ernest T","family":"Chivero","sequence":"additional","affiliation":[{"name":"Iowa City Veterans Affairs Medical Center , Iowa City, IA 52242"},{"name":"Interdisciplinary Program in Molecular and Cellular Biology, University of Iowa , Iowa City, IA 52242"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jack T","family":"Stapleton","sequence":"additional","affiliation":[{"name":"Iowa City Veterans Affairs Medical Center , Iowa City, IA 52242"},{"name":"Interdisciplinary Program in Molecular and Cellular Biology, University of Iowa , Iowa City, IA 52242"},{"name":"Department of Internal Medicine, University of Iowa , Iowa City, IA 52242"},{"name":"Department of Microbiology, University of Iowa , Iowa City, IA 52242"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2013,6,15]]},"reference":[{"key":"2025032407081527000_r1","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1099\/vir.0.027490-0","article-title":"The GB viruses: a review and proposed classification of GBV-A, GBV-C (HGV), and GBV-D in genus Pegivirus within the family Flaviviridae","volume":"92","author":"Stapleton","year":"2011","journal-title":"J. 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