Bioinformatics Studies of Human Viruses

Gonzalez-Delgado博士使用序列程序HMMer和Pfam蛋白域数据库建立了一个半自动管道，以确定病毒蛋白的功能。该管道获取人类病毒的基因组，提取带注释的基因，然后运行HMMer来找到组成病毒蛋白质的结构域。一旦发现具有统计学意义的Pfam结构域，就会再次查询Pfam，以发现对给定结构域有贡献的蛋白质中哪些是人类的。人类蛋白质成为病毒与其人类宿主之间先前水平基因转移的候选者。为了向该项目提供与实验病毒学家相关的问题，Gonzalez-Delgado博士咨询了。DeVico和Lewis是人类病毒学研究所的人类免疫缺陷病毒（HIV）专家。

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?