Proteins Involved in Orthopoxvirus Intracellular Egress

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DESCRIPTION (provided by applicant): Poxviruses include a large family of DNA viruses capable of infecting and causing disease in humans. While the most notorious member variola, the causative agent of smallpox, was eradicated from natural infection, there are still concerns about a clandestine release during a biological attack. In addition, monkeypox and other members of the family have raised concern about epizootic infections capable of causing epidemic. Poxviruses produce two infectious forms, enveloped and unenveloped virions. While unenveloped virions make up the majority of their progeny, it is the enveloped form that is required for efficient cell-to-cell spread and infection. Envelopment occurs in the cytoplasm of infected cells and only 7 proteins encoded by the virus are known to be unique to the enveloped form. The long-term goal of this project is to understand how these 7 proteins coordinate the monumental task of creating and releasing an enveloped virion. The immediate goal is to understand the function of the protein encoded by F12L. Our Hypothesis is that F12 interacts with the actin motor myosin V to facilitate virion transport through the actin cortex for egress. Our specific aims are: 1) Test for functional domains of F12, 2) Characterization of the kinesin-A36-F12 interaction, 3) Screen for additional proteins that interact with F12 and MyoV. The results obtained will provide greater insight into the interaction poxviruses have with their host at a molecular level and give us a better understanding of poxvirus morphogenesis and egress. PUBLIC HEALTH RELEVANCE: Even though natural occurring smallpox was eradicated, concern for orthopoxviruses, ranging from a clandestine release of smallpox to outbreaks of epizootic infections such as monkeypox, still exist. Understanding the biology of poxviruses is still a priority not only for preventing epidemics but also for understanding basic mechanisms of biology. The results from this study will provide new insights into poxvirus infections, which will provide new targets for antivirals and treatments against their infections.