Cellular protein identified as possible drug target to combat Lassa hemorrhagic fever: Experimental approach could uncover new treatment options for the virus, which is highly prevalent in Western Africa

Scripps Research in collaboration with the La Jolla Institute for Immunology have used a novel strategy to identify and study host cell proteins that contribute to multiplication of Lassa virus, a virus that causes a severe hemorrhagic fever disease. The discovery could lead to potential new drug targets for treating the disease.

Lassa virus (LASV) is highly prevalent in Western Africa. The virus is typically transmitted to humans via contact with aerosols or the droppings and secretions of infected rodents. Infected individuals can develop Lassa fever (LF), a hemorrhagic fever disease associated with high morbidity and mortality. Notably, many LF survivors experience long-term side effects including sensory-neural hearing loss. Other than off-label use of ribavirin- which is of limited and controversial efficacy- there are no treatments for LF, nor any licensed vaccines.

The research, led by Juan Carlos de la Torre, PhD, of Scripps Research, in collaboration with the laboratory of Erica Ollmann Saphire, PhD, at La Jolla Institute for Immunology, was published in the Proceedings of the National Academy of Sciences (PNAS) on July 18, 2022.

To identify host cell proteins that contribute to LASV replication, the researchers implemented a new strategy that combined proximity proteomics with the use of a non-infectious cell-based LASV minigenome system that recreates the molecular processes involved in LASV replication. Proximity proteomics fuses a protein of interest to an enzyme that will label nearby proteins with a chemical tag, which facilitates their identification.

“Viruses don’t operate in isolation,” says Saphire. “They hijack and require molecules of the cell for their own purposes.”

De la Torre compares the process to the way social networks can “leave traces of interactions” and provide information about how people might relate to one another, for example, whether two users are located in the same city or household, or if they are family members or acquaintances.

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