Dr. Nicholas Chesarino, assistant professor of biology at The University of Akron, is part of a research team awarded a five-year R01 grant from the National Institutes of Health to investigate how viruses evolve to overcome the natural defenses of new host species.

The project, “Resolving the evolutionary acquisition of broad APOBEC3 neutralization by primate lentiviral Vif,” is funded by the National Institute of Allergy and Infectious Diseases (NIAID) and led by Dr. John Gross at the University of California, San Francisco. Chesarino is a co-investigator on the project, alongside Dr. Ignacia Echeverria, also at the University of California, San Francisco, and Dr. Molly Ohainle at the University of California, Berkeley.

As part of the R01, Chesarino’s laboratory at UA will receive a subaward totaling $490,255 over five years.

The project addresses a fundamental question in virology: How does a virus adapt well enough to jump from one species to another?

Understanding how viruses cross species barriers

Cells possess an array of antiviral proteins that act as an early line of defense against viral infection. Among them are proteins in the APOBEC3 family, which can block Human Immunodeficiency Virus (HIV) and related lentiviruses from replicating. In response, these viruses produce a protein called Vif that disables APOBEC3 defenses and enables infection. This antagonistic relationship gives rise to what is known as a host-virus evolutionary arms race, where host cells mount antiviral defenses, and viruses adapt to overcome them. The results of these arms races can influence whether a virus remains restricted to one species or gains the ability to infect another.

Tracing the different evolutionary paths of HIV

The research team is invested in understanding the viral adaptations that enabled HIV to become a human pathogen. Importantly, HIV is not a single virus; HIV-1 and HIV-2 are related but distinct viruses that emerged from separate instances of lentiviruses jumping from primates to humans. HIV-1 traces back to viruses that infect chimpanzees, and its spread is responsible for the AIDS pandemic. HIV-2 traces back to a different virus that infects sooty mangabey monkeys in West Africa. The unique origins of HIV-1 and HIV-2 are reflected in their Vif proteins: while HIV-1 Vif required adaptations to disable chimpanzee and human APOBEC3 proteins, HIV-2 Vif was largely pre-equipped to facilitate transmission directly from monkeys to humans.

How the virus that gave rise to HIV-2 already had the broad, built-in ability to neutralize human APOBEC3 proteins, without prior adaptation, has remained unclear. This project will investigate the molecular basis for this ability, to better understand how some viruses are poised to readily cross species barriers. The investigators will combine evolutionary analysis, structural biology, molecular modeling, and laboratory experiments to determine how changes in viral Vif proteins allow them to neutralize host APOBEC3 proteins. Understanding the molecular events that gave rise to HIV-1 and HIV-2 can reveal broader principles governing viral evolution, cross-species transmission, and the emergence of new infectious diseases. The work may also help identify new approaches for combating HIV infection.

Building on new discoveries about HIV-2

The project builds directly on research Chesarino and his collaborators recently published in Nature Communications. In that study, the team used cryo-electron microscopy to reveal how HIV-2 Vif binds to and disables the human antiviral protein APOBEC3H. The work uncovered molecular interactions that distinguish HIV-2 from HIV-1 and provide clues to how the two viruses followed different evolutionary paths in adapting to human hosts.

For Chesarino, the award represents an important milestone for a research program that is still relatively new to UA. He joined the Department of Biology as an assistant professor in August 2025. His laboratory studies the genetic conflicts that occur between viruses and the hosts they infect, with an emphasis on understanding how antiviral defenses and viral countermeasures evolve over time.

Creating research opportunities for UA students

The new funding will also create opportunities for UA undergraduate and graduate students to participate directly in federally funded biomedical research. Chesarino has made student participation a central component of his laboratory, including through the Department of Biology’s Tiered Mentoring program. Students in his group gain experience in areas such as bioinformatics, evolutionary analysis, cell and molecular biology, tissue culture, and the study of host-virus protein interactions.

“The most exciting part of this grant funding is the chance to train the next generation of infectious disease researchers,” Chesarino said. “Fundamental questions regarding HIV biology still remain, and I’m looking forward to supporting UA students as they address them.”

The R01 was awarded in July 2026 and is scheduled to continue through June 2031. The project is supported by the National Institute of Allergy and Infectious Diseases of the National Institutes of Health under award 1R01AI202673-01.