Respiratory syncytial virus F glycoprotein was shown to interact with RhoA and RhoA-derived peptides were shown to inhibit RSV infection in vitro and in a murine model. In addition, RhoA-derived peptides inhibited other viruses (Parainfluenza virus Type 3 and HIV-1) with similar glycoprotein-mediated membrane fusion mechanisms. Further studies showed that RhoA was activated during RSV infection and that inhibiting RhoA activation could alter the syncytium-forming capacity of the virus, and virus morphogenesis, resulting in less filamentous virus. Inhibiting RhoA targeting to membrane through isoprenylation inhibition, could diminish RSV replication and reduce pathogenicity in the murine model. In part, this works through shifting the assembly of RSV from cholesterol-rich lipid microdomains to other regions of the membrane. Lipid microdomains have been shown to be involved in the assembly and production of a number of viruses, including HIV-1, influenza, hepatitis C, and rotavirus. This work investigates the role of lipid microdomains in formation of RSV and severe acute respiratory syndrome coronavirus coronavirus (SARS-CoV) by examining the colocalization of viral proteins with lipid microdomain components and by evaluating the effects of lipid raft disruption on viral infectivity. The SARS-Co) encodes 4 main structural proteins, M, N, E, and S, three of which mediate SARS-CoV pseudo particles. These particles preferentially bud from lipid rafts, and disruption of lipid rafts with cyclodextrin diminishes particle formation.

National Institute of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
Intramural Research (Z01)
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