{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,6,13]],"date-time":"2026-06-13T14:14:19Z","timestamp":1781360059778,"version":"3.54.1"},"posted":{"date-parts":[[2023,11,4]]},"group-title":"Immunology","reference-count":86,"publisher":"openRxiv","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2023,11,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                <jats:p>\n                  Infection by chikungunya virus (CHIKV), a mosquito-borne alphavirus, causes severe polyarthralgia and polymyalgia, which can last in some people for months to years. Chronic CHIKV disease signs and symptoms are associated with the persistence of viral nucleic acid and antigen in tissues. Like humans and nonhuman primates, CHIKV infection in mice results in the development of robust adaptive antiviral immune responses. Despite this, joint tissue fibroblasts survive CHIKV infection and can support persistent viral replication, suggesting that they escape immune surveillance. Here, using a recombinant CHIKV strain encoding a chimeric protein of VENUS fused to a CD8\n                  <jats:sup>+<\/jats:sup>\n                  T cell epitope, SIINFEKL, we observed a marked loss of both MHC class I (MHC-I) surface expression and antigen presentation by CHIKV-infected joint tissue fibroblasts. Both\n                  <jats:italic>in vivo<\/jats:italic>\n                  and\n                  <jats:italic>ex vivo<\/jats:italic>\n                  infected joint tissue fibroblasts displayed reduced cell surface levels of H2-K\n                  <jats:sup>b<\/jats:sup>\n                  and H2-D\n                  <jats:sup>b<\/jats:sup>\n                  MHC proteins while maintaining similar levels of other cell surface proteins. Mutations within the methyl transferase-like domain of the CHIKV nonstructural protein 2 (nsP2) increased MHC-I cell surface expression and antigen presentation efficiency by CHIKV-infected cells. Moreover, expression of WT nsP2 alone, but not nsP2 with mutations in the methyltransferase-like domain, resulted in decreased MHC-I antigen presentation efficiency. MHC-I surface expression and antigen presentation could be rescued by replacing VENUS-SIINFEKL with SIINFEKL tethered to \u03b22-microglobulin in the CHIKV genome, which bypasses the need for peptide processing and TAP-mediated peptide transport into the endoplasmic reticulum. Collectively, this work suggests that CHIKV escapes the surveillance of antiviral CD8\n                  <jats:sup>+<\/jats:sup>\n                  T cells, in part, by nsP2-mediated disruption of MHC-I antigen presentation.\n                <\/jats:p>\n                <jats:sec>\n                  <jats:title>AUTHOR SUMMARY<\/jats:title>\n                  <jats:p>\n                    Arthritogenic alphaviruses, including chikungunya virus (CHIKV), are re-emerging global public health threats with no approved vaccines or antiviral therapies. Infection with these viruses causes debilitating musculoskeletal disease for months to years that is associated with the persistence of viral RNA and antigen. Prior studies using a mouse model found that CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells, which recognize viral peptides in the context of major histocompatibility class I (MHC-I) displayed on the surface of infected cells, have a limited role in the control and clearance of CHIKV infection in joint-associated tissues, suggesting that CHIKV infected cells evade these critical effectors of the anti-viral immune response. Here, we show that MHC-I antigen presentation is inefficient in CHIKV-infected joint tissue fibroblasts, and that a protein encoded by CHIKV and produced in infected cells, nonstructural protein 2 (nsP2), disrupts the surface display of MHC-I molecules and antigen recognition of infected cells by CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells. Our findings support a role for CHIKV nsP2 in the evasion of the CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cell response and establishment of persistent infection.\n                  <\/jats:p>\n                <\/jats:sec>","DOI":"10.1101\/2023.11.03.565436","type":"posted-content","created":{"date-parts":[[2023,11,5]],"date-time":"2023-11-05T00:50:13Z","timestamp":1699145413000},"source":"Crossref","is-referenced-by-count":3,"title":["Chikungunya virus infection disrupts MHC-I antigen presentation via nonstructural protein 2"],"prefix":"10.64898","author":[{"given":"Brian C.","family":"Ware","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. 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