Vesicular stomatitis virus (VSV) is both an interesting model of negative-strand RNA viruses like influenza and rabies, and a potential weapon to fight cancer and HIV. Researchers at UCLA have now deduced the three dimensional structure of the virus, opening up the practical possibility of modifying it into a disease killing pathogen.
Based on their research into the structure of VSV, the team proposed a model for the assembly of the virus, with its origin at the bullet tip. Their data suggest that VSV assembles through the alternating use of several possible interaction interfaces coded in viral protein sequences to wind its protein and RNA chain into the characteristic bullet shape.
“Our structure provides the first direct visualization of the N and M proteins inside the VSV virion at 10.6-Ã… resolution. Surprisingly, our data clearly demonstrated that VSV is a highly ordered particle, with the nucleocapsid surrounded by, instead of surrounding, a matrix of M proteins,” said lead study author Peng Ge, a visiting graduate student at UCLA from Baylor College of Medicine. “To our amusement, the sequence in assembling viral protein and RNA molecules into the virus appears to rhyme with the first several measures of Mozart’s piano sonata in C-Major, K.545.” (This musical correlation is illustrated in the paper’s supplementary movie 2.)
The findings could help lead to advances in the development of VSV-based vaccines for HIV and other deadly viruses, according to the researchers.
“Our structure provides some of the first clues for understanding VSV-derived vaccine pseudotypes and for optimizing therapeutic VSV variants,” Zhou [Z. Hong Zhou, UCLA professor of microbiology, immunology and molecular genetics] said. “This work moves our understanding of the biology of this large and medically important class of viruses ahead in a dramatic way. The next stage of research for our team will be to reveal the details of molecular interactions at the atomic scale using advanced imaging instruments now available at CNSI.”