Project Grant 2302677

COLLABORATIVE RESEARCH: PURSUIT: SYSTEMATIC VIRAL DISCOVERY THROUGH STRUCTURED SEARCH OF HOST PHYLOGENY -VIRAL PATHOGENS ARE USUALLY RESEARCHED INTENSIVELY AFTER THEY EMERGE AND CAUSE DISEASE IN HUMANS OR DOMESTIC ANIMALS. THIS LEADS TO A DEEP UNDERSTANDING OF THE FEW VIRUSES THAT AFFECT HUMANS, BUT LARGELY IGNORES THE VAST, UNKNOWN DIVERSITY OF VIRUSES IN THE REST OF MAMMALS. THIS PROJECT LEVERAGES THE HIGH-QUALITY, CRYOGENICALLY FROZEN TISSUE COLLECTIONS OF WILD MAMMALS THAT ARE STORED IN NATURAL HISTORY MUSEUMS TO SYSTEMATICALLY SEQUENCE, DISCOVER, AND CHARACTERIZE VIRAL DIVERSITY FROM ACROSS THE MAMMAL TREE OF LIFE. THIS PROJECT WILL CONTRIBUTE DIRECTLY TO THE UNDERSTANDING OF HOST-VIRUS EVOLUTION, INFORM THE FREQUENCY AND DISTANCE AT WHICH ?SPILLOVER? OR HOST-SWITCHES CAN OCCUR, AND IDENTIFY HIGH AND LOW RISK VIRAL PATHOGENS. BY CONNECTING THE VIRAL SEQUENCES BACK TO A PHYSICAL MAMMAL SPECIMEN AT A MUSEUM, THIS PROJECT PROVIDES A FOUNDATION FOR DETAILED FUTURE INVESTIGATIONS OF SPECIFIC PATHOGENS, PATHOGEN COMMUNITIES, AND THE ASSOCIATED GENETIC VARIATION IN THEIR MAMMAL HOSTS. TO FURTHER REINFORCE THE CONNECTION BETWEEN MICROBIAL RESEARCH AND NATURAL HISTORY MUSEUMS, THIS PROJECT WILL COLLABORATE WITH PROJECT ECHO?S MUSEUMS AND EMERGING PATHOGENS IN THE AMERICAS (MEPA) NETWORK TO FOSTER INTERNATIONAL EXCHANGE OF IDEAS AND BUILD CAPACITY IN BIODIVERSE COUNTRIES, WHERE PATHOGEN EMERGENCE IS MORE LIKELY. THIS PROJECT USES A SAMPLING STRATEGY THAT OPTIMIZES EVOLUTIONARY DISTANCES AND GEOGRAPHIC COVERAGE TO SELECT MAMMAL SPECIMENS TO SURVEY FOR VIRUSES. INITIALLY, A CORE SET OF NEARLY 600 MAMMALIAN SPECIES IN 25 OF 27 ORDERS WILL BE TARGETED TO PROVIDE A MAMMAL-WIDE SURVEY OF VIRAL DIVERSITY. BASED ON THIS INITIAL EFFORT, LINEAGES THAT HAVE ESPECIALLY RICH VIRAL COMMUNITIES WILL BE SELECTED FOR MORE INTENSIVE SAMPLING THAT WILL ALLOW FOR ANALYSES OF VIRUS-VIRUS INTERACTIONS AND HOST-VIRUS CO-EVOLUTION (OR LACK THEREOF). NEW AND KNOWN VIRAL SEQUENCES WILL BE RECONSTRUCTED BIOINFORMATICALLY AND USED TO TEST LONG-STANDING ASSUMPTIONS RELATED TO VIRAL DIVERSITY, HOST TRAITS, AND HOST DIVERSITY, INCLUDING WHICH LINEAGES REPRESENT ?HIGH RISK? OR ?LOW RISK? TO HUMANS (E.G., BATS, RODENTS, AND PRIMATES AS TRADITIONALLY ?HIGH RISK? GROUPS). PAIRS OF MAMMAL AND VIRUS LINEAGES THAT SHOW ELEVATED RATES OF HOST SWITCHING WILL BE USED TO IDENTIFY THE ECOLOGICAL AND ENVIRONMENTAL TRAITS THAT ARE ASSOCIATED WITH SUCH EVENTS. THIS AWARD REFLECTS NSF'S STATUTORY MISSION AND HAS BEEN DEEMED WORTHY OF SUPPORT THROUGH EVALUATION USING THE FOUNDATION'S INTELLECTUAL MERIT AND BROADER IMPACTS REVIEW CRITERIA.