Bioinformatics Studies of Human Viruses

点击翻译按钮获取中文摘要

Dr. Gonzalez-Delgado set up a semi-automated pipeline using the alignment program HMMer and the Pfam protein domain database, to identify the functionality of viral proteins. The pipeline takes the genome of a human virus, extracts the annotated genes, and runs HMMer to find the domains composing a viral protein. Once statistically significant Pfam domains have been found, Pfam is again queried, to discover which of the proteins contributing to a given domain are human. The human proteins become candidates for a previous horizontal gene transfer between the virus and its human host. To inform the project with questions relevant to experimental virologists, Dr. Gonzalez-Delgado consulted with Drs. DeVico and Lewis, human immunodeficiency virus (HIV) experts at the Institute of Human Virology. The project has resulted in a submitted manuscript examining human herpes virus 8 (HHV-8) as a model virus, where HGT with the human genome are relatively well characterized. HHV-8 shares at least 36% of its genes with the human host: 17 known and 12 potentially new genes were identified as candidates for HGT, despite previous intense experimental scrutiny. To compare the frequency of HGT across viruses, the manscript surveyed 10 other viruses impacting human health, concluding that HGT probably occurs between humans and both DNA and RNA viruses, in viral genomes of differing sizes, regardless of DNA transcription strategies. Of special note are the Human T-lymphotropic viruses, where genes involved in HGT possibly have a frequency as high as 73%. Dr. Gonzalez-Delgado is now analyzing sequences of the simian immunodeficiency virus, which infects macaques. The SIV-macaque system provides an animal model for HIV infection, to answer a question posed by Drs. Lewis and Devico: are the sequences of the infecting and non-infecting HIV particles in a viral inoculum statistically distinguishable?