Multi-pronged human protein mimicry by SARS-CoV-2 reveals bifurcating potential for MHC detection and immune evasion
Abstract: The hand of molecular mimicry in shaping SARS-CoV-2 evolution and immune evasion remains to be deciphered. Here, we identify 33 distinct 8-mer/9-mer peptides that are identical between SARS-CoV-2 and human proteomes, including 20 novel peptides not observed in any previous human coronavirus (HCoV) strains. Four of these mimicked 8-mers/9-mers map onto HLA-B*40:01, HLA-B*40:02, and HLA-B*35:01 binding peptides from human PAM, ANXA7, PGD, and ALOX5AP proteins. This striking mimicry of multiple human proteins by SARS-CoV-2 is made more salient by the targeted genes being focally expressed in arteries, lungs, esophagus, pancreas, and macrophages. Further, HLA-A*03 restricted 8-mer peptides are shared broadly by human and coronaviridae helicases with primary expression of the mimicked human proteins in the neurons and immune cells. These findings highlight molecular mimicry as a shared strategy adopted by evolutionary titans — the virus in its quest for escaping herd immune surveillance, and the host immune systems that are constantly learning the patterns of ‘self’ and ‘non-self’.
Competing Interest Statement
AJV, NK, PA and VS are employees of nference and have financial interests in the company. ADB is a consultant for Abbvie, is on scientific advisory boards for Nference and Zentalis, and is founder and President of Splissen therapeutics. One or more of the investigators associated with this project and Mayo Clinic have a Financial Conflict of Interest in technology used in the research and that the investigator(s) and Mayo Clinic may stand to gain financially from the successful outcome of the research. This research has been reviewed by the Mayo Clinic Conflict of Interest Review Board and is being conducted in compliance with Mayo Clinic Conflict of Interest policies.