{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T00:25:28Z","timestamp":1791246328933,"version":"4.1.0"},"posted":{"date-parts":[[2025,7,28]]},"group-title":"Systems Biology","reference-count":98,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,7,28]],"date-time":"2025-07-28T00:00:00Z","timestamp":1753660800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.biorxiv.org\/about\/FAQ#license"}],"funder":[{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"crossref","award":["U19AI135990"],"award-info":[{"award-number":["U19AI135990"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"crossref","award":["U19AI135972"],"award-info":[{"award-number":["U19AI135972"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2025,7,28]]},"abstract":"<jats:title>Summary<\/jats:title>\n                <jats:p>\n                  Coronaviruses, including SARS-CoV-2, can cause severe disease in humans, whereas reservoir hosts like\n                  <jats:italic>Rhinolophus<\/jats:italic>\n                  bats remain asymptomatic. To investigate how host-specific protein-protein interactions (PPIs) influence infection, we generated comparative PPI maps for SARS-CoV-2 and its bat-origin relative RaTG13 using affinity purification-mass spectrometry (AP-MS) in human and\n                  <jats:italic>Rhinolophus ferrumequinum<\/jats:italic>\n                  (RFe) bat cells. This approach identified both conserved and virus- and host-specific interactions that regulate infection dynamics. Notably, SARS-CoV-2 required a non-synonymous mutation in nucleocapsid to replicate in bat cells expressing human ACE2 and TMPRSS2. Analysis of the viral protein Orf9b revealed differential interactions with mitochondrial proteins Tom70 and MTARC2. A single residue difference in Orf9b between SARS-CoV-2 and RaTG13 functions as a molecular switch, weakening Tom70 binding and immune evasion in human cells while enhancing interaction with the bat-specific restriction factor MTARC2. These findings demonstrate how a single-residue substitution can reshape virus-host interactions and contribute to immune evasion and host adaptation.\n                <\/jats:p>","DOI":"10.1101\/2025.07.26.666918","type":"posted-content","created":{"date-parts":[[2025,7,29]],"date-time":"2025-07-29T04:35:11Z","timestamp":1753763711000},"source":"Crossref","is-referenced-by-count":3,"title":["Coronavirus protein interaction mapping in bat and human cells identifies molecular and genetic switches for immune evasion and 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