VIRAL REGULATION OF IMMUNITY AND BIOINFORMATIC ANALYSIS

Abstract

Smallpox, eradicated in 1980, remains a historic milestone in medical science as well as a testament to the power of vaccines. However, its vaccine has remained relatively unchanged and continues to be one of the more risk-associated vaccines in modern medicine. The risk of smallpox vaccination (ACAM2000 Vaccine) lies in the fact that it uses the live vaccinia virus, a less virulent relative of smallpox that retains a degree of virulence in humans. Our lab uses bioinformatics to analyze sequences and study particular genes of vaccinia virus and how they contribute to virulence. We are studying the differences between A35- Knockout, O1L Knockout and wild type vaccinia virus in terms of virulence and immune responses. Our lab hypothesized and demonstrated that the deletion of virulence gene sequence A35 in vaccinia virus resulted in dampening of viral pathogenesis. Immune responses of mice vaccinated with A35 Knockout were significantly higher than the immune responses of wild-type vaccinated mice. The functions of the A35 and O1L genes are currently unknown, but we are using bioinformatics to explore homologous sequences in databases to develop hypotheses for these gene functions. In addition, we will explore sequence motifs within A35 and O1L that might give clues to their biochemical functions. These data will aid in understanding poxvirus virulence/pathogenesis. The improved immune response to A35 Deletion shows that this version of the virus could prove fruitful for not only a safer smallpox vaccine, but it could also be used as a recombinant vaccine against many other infectious diseases and cancer.