** AWARDS ISSUED PRIOR TO JANUARY 20, 2025, WERE FUNDED UNDER PREVIOUS ADMINISTRATIONS AND MAY NOT REFLECT THE PRIORITIES AND POLICIES OF THE CURRENT ADMINISTRATION.** SEVERE ACUTE RESPIRATORY SYNDROME CORONAVIRUS 2 (SARS-COV-2) HAS A BROAD HOST RANGE WITH MULTIPLE SPILLOVER EVENTS OF HUMAN-TO-ANIMAL TRANSMISSION DOCUMENTED. THESE OBSERVATIONS SUGGEST A RELATIVELY LOW SPECIES BARRIER BETWEEN HUMANS AND ANIMALS. HOWEVER, THE MECHANISMS UNDERLYING SPECIES SPECIFICITY AND SUSCEPTIBILITY TO SARS-COV-2 REMAIN POORLY UNDERSTOOD.THE OVERALL GOALS OF THE PRESENT STUDY ARE TO DETERMINE THE MECHANISMS UNDERLYING HOST SUSCEPTIBILITY OR RESTRICTION TO SARS-COV-2 INFECTION AND TO IMPROVE OUR UNDERSTANDING OF THE ANIMAL SPECIES AT RISK OF NATURAL INFECTION WITH SARS-COV-2. THE SPECIFIC OBJECTIVES OF THE PROPOSED STUDY ARE:(1) TO IDENTIFY THE MECHANISMS UNDERLYING SARS-COV-2 HOST RANGE AND ANIMAL SPECIES SPECIFICITY AT THE CELLULAR LEVEL.(2)TO CHARACTERIZE THE FACTORS AFFECTING SARS-COV-2 SUSCEPTIBILITY AT THE ORGANISM LEVEL; AND(3)TO INVESTIGATE NATURAL EXPOSURE OF ANIMALS TO VARIANT SARS-COV-2 STRAINS THROUGH SURVEILLANCE. THE PROPOSED STUDY DIRECTLY ALIGNS WITHAPHIS' AMERICAN RESCUE PLAN STRATEGIC FRAMEWORK AND ADDRESSES SEVERAL IMPORTANT RESEARCH PRIORITY AREAS IDENTIFIED IN THE APHIS-AFRI NIFA COLLABORATION ON SARS-COV-2 ANNOUNCEMENT: I. EXPAND KNOWLEDGE OF SUSCEPTIBILITY OF ANIMAL SPECIES TO SARS-COV-2; II. ADDRESS GAPS IN SURVEILLANCE AND INVESTIGATION ACTIVITIES FOR SARS-COV-2 IN ANIMALS; AND III. IDENTIFY RISKS AT THE HUMAN-ANIMAL INTERFACE THAT MAY ALLOW IMPLEMENTATION OF MEASURES TO PREVENT TRANSMISSION OR SARS-COV-2 TO ANIMALS AND REDUCE POTENTIAL IMPACTS TO THE FOOD SUPPLY. THE KNOWLEDGE GAINED WITH THESE STUDIES WILL ALLOW THE DESIGN OF STRATEGIES FOR EFFECTIVE PREVENTION AND CONTROL OF SARS-COV-2 AT THE HUMAN-ANIMAL INTERFACE.