© Research
Publication : bioRxiv : the preprint server for biology

Coronavirus protein interaction mapping in bat and human cells identifies molecular and genetic switches for immune evasion and replication.

Team: Virus sensing and signaling
Member: Nolwenn Jouvenet
Scientific Fields
Diseases
Organisms
Applications
Technique

Published in bioRxiv : the preprint server for biology - 28 Jul 2025

Batra J, Rutkowska M, Zhou Y, Ye C, Adavikolanu R, Young JM, Anand D, Verma S, Gordon M, Malpotra S, Cupic A, Kehrer T, Moen JM, Winters DM, Rojc A, Mena I, Aslam S, Martinez-Romero C, Conde Viñas I, Khalil Z, Farrugia K, Banerjee A, Tussia-Cohen D, Santos MD, Maji S, Muralidharan M, Foussard H, Chen IP, Fuchs R, Felipe CS, Zuliani-Alvarez L, Choudhury P, Obernier K, Gracias S, Suryawanshi R, Ibáñez C, Juste J, Pache L, Taha TY, Jouvenet N, Verba KA, Fraser JS, Demeret C, Stroud RM, van Bakel H, Ott M, Hagai T, Polacco B, Swaney DL, Echeverria I, Bouhaddou M, Eckhardt M, Malik HS, Martinez-Sobrido L, Miorin L, García-Sastre A, Krogan NJ

Link to Pubmed [PMID] – 40766693

Link to DOI – 10.1101/2025.07.26.666918

bioRxiv 2025 Jul; ():

Coronaviruses, including SARS-CoV-2, can cause severe disease in humans, whereas reservoir hosts like Rhinolophus 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 Rhinolophus ferrumequinum (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.