[DP2] Deciphering long-term virus evolution through the reconstruction of past viral genomes
Ente: National Institute of Allergy and Infectious Diseases
Scadenza: 2028-07-31
Importo max: 509.299 EUR
Paese: US
Descrizione
Project Summary
Viruses have imposed a significant global burden of morbidity and mortality for millennia and continue to pose
major threats to public health in the United States. Just in the last century, highly pathogenic RNA viruses such
as influenza A, HIV and SARS-CoV-2 resulted in devastating pandemics that directly impacted millions of
individuals and altered socioeconomic dynamics. Fueled by major advances in sequencing during the last
decades, the emerging field of archeovirology has begun identifying viruses that severely impacted humans
prior to the 20th century. To this day, however, the pathogens responsible for important past epidemics are still
unknown and there are significant gaps remaining in the evolutionary history of certain viral families, especially
for RNA viruses. Using a highly collaborative and innovative approach to overcome intrinsic limitations in the
identification of viral genomes from human remains, this proposal will uncover the viral diversity that existed
during periods of notable epidemic outbreaks and expand our knowledge of the origins and evolution of highly
pathogenic viruses. In particular, this proposal seeks to identify and characterize genomes from centuries-old
RNA viruses, a goal that so far has remained elusive. Using well-established ancient DNA techniques, forensic
proteomics, and improved RNA isolation methodologies, our team will reconstruct viral genomes from human
remains and preserved lung specimens from unique collections spanning major historical disease outbreaks to
answer questions of broad relevance to viral emergence, long-term viral evolution, and human disease. Guided
by archeological and historical documentation, this work will identify viruses that existed in the past ~500
years, study their origin and evolutionary relationships to modern viruses, and characterize the evolution of
viral protein function in relation to their human hosts. Together, this proposal will generate a comprehensive
characterization of the properties of past viral infections that will not only lead to the identification of viruses
responsible for epidemics that profoundly altered human history but will also uncover evolutionary adaptations
between past and present viruses and define the origins of highly pathogenic RNA viruses, providing key
molecular information to combat viral pathogens that affect, or have the potential to affect, the health of
Americans.
Istituzione: FRED HUTCHINSON CANCER CENTER
PI: Daniel Blanco-Melo
Progetto: 5DP2AI177896-04
Settori: National Institute of Allergy and Infectious Diseases
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