Characteristics and consequences of rotavirus exploitation of extracellular vesicles for intercellular transmission - although non-enveloped viruses like rotaviruses were believed to exit host cells…

The National Institute of Allergy and Infectious Diseases awarded the Research Foundation of The City University of New York $348,615 on May 1, 2026, under the Allergy and Infectious Diseases Research program (CFDA 93.855) to characterize how rotaviruses exploit extracellular vesicles for intercellular transmission and assess the evolutionary consequences of this non-lytic infection mechanism.

The funded work will examine whether genetically distinct rotaviruses can be co-packaged into the same microvesicle to facilitate collective infection, perform serial passaging experiments comparing microvesicle-facilitated infections with free particle infections to determine if the former enables faster evolutionary adaptation, and use duplex sequencing to assess genetic diversity in evolved populations and test whether microvesicle carriage increases diversity by promoting coinfection and genome mixing. The research aims to determine whether targeting microvesicle-facilitated transmission could slow the acquisition of antiviral drug and vaccine resistance, with long-term goals of uncovering new treatments that target this transmission mechanism.

Research Foundation of The City University of New York, doing business as Rfcuny - Queens College, is a non-profit research administration entity serving as the fiscal agent for Queens College. Work is performed in Flushing, New York. The award runs through April 30, 2028, as a project grant with $348,615 obligated.

Characteristics and consequences of rotavirus exploitation of extracellular vesicles for intercellular transmission - although non-enveloped viruses like rotaviruses were believed to exit host cells only via lysis, recent evidence shows they can exit non-lytically in extracellular vesicles, which are then used to infect new host cells. This new infection mode allows collective infection of new host cells and has implications for viral biology, evolution, and pathogenesis. The long-term goal is to uncover new treatments that target this transmission mechanism. However, many basic questions remain regarding MV use by viruses. The objective of this proposal is to characterize microvesicle (MV) facilitated rotavirus infections and assess their evolutionary consequences. We will pursue these aims using an innovative combination of analytical and manipulative techniques drawn from fields ranging from molecular to evolutionary biology. Our primary aim is to examine the evolutionary consequences of collective infection. To better understand how collective infection can facilitate recombination and reassortment, we will test if genetically distinct rotaviruses can be CO-packaged into the same MV. Next, we will perform serial passaging experiments with either MV-facilitated infections or free particle infections to determine if MV-facilitated infections allow for faster evolutionary adaptation. We will also assess the genetic diversity of evolved populations using duplex sequencing to test the hypothesis that MV-carriage increases genetic diversity by promoting coinfection and genome mixing. The rationale for these experiments is to determine if MV-facilitated transmission can be targeted to slow down the acquisition of antiviral drug/vaccine resistance. The expected outcome of this work is a deeper understanding the how rotaviruses exploit MVS for transmission and the main benefits that they accrue. The proposed work is significant because IT will permit the prioritization of therapeutic targets. The proposed work also supports the training of undergraduate students at an institution that is a key COG in facilitating social mobility among first-generation and financially disadvantaged college students.