LCMV particle formation: There�s more than 1 way to make an arenavirus DIP
Van Beek, Emily
Van Beek, Emily
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Abstract
The arenavirus matrix protein Z is a multifunctional regulator of the viral life cycle, including driving the assembly and release of viral particles, suppressing type I interferon signaling, and modulating viral RNA synthesis. These actions are coordinated through interactions with both viral and host factors, yet the specific Z sequence determinates underlying these diverse functions remain incompletely defined. We sought to define the key regions of Z that drive these various functions using a scanning alanine mutagenesis approach across the entire lymphocytic choriomeningitis mammarenavirus (LCMV) Z open reading frame to systematically identify regions important for the viral life cycle. Our previous studies showed that LCMV defective interfering particle (DIP) production is driven by the Z-encoded PPxY late domain via engagement with cellular NEDD4 E3 ubiquitin ligases and ESCRT components, while infectious particle production is independent of this pathway. Notably, recombinant LCMV lacking a functional PPxY late domain no longer produces DIPs but still generates infectious particles, albeit with slightly delayed kinetics. Extending these findings, our scanning alanine mutagenesis screen identified at least six additional residues of LCMV Z that are critical for driving DIP formation while dispensable for the generation of infectious virions. These findings suggest LCMV DIP production may be governed by additional, non-late domain mediated regulatory mechanism(s) within the Z protein. Together, this work provides mechanistic insights into the molecular regulation of arenavirus infectivity and highlights the complex regulation of small viral proteomes during the viral life cycle.
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Date
1/1/2026
Student Status
Graduate Student
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Poster
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I am in the Cellular Molecular and Biomedical Sciences (CMB) Program
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Larner College of Medicine
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Life Science