Wang Lab Research

We are interested in the identification and characterization of novel viruses. The rationale for these efforts is twofold: (1) to identify novel etiologies of human disease; (2) to exploit novel viruses as exquisite probes of host processes to uncover novel aspects of fundamental biology. In our work, we integrate a variety of experimental methodologies that cross many disciplines including molecular biology, classic virology, genomics, epidemiology, clinical investigation and bioinformatics.

Genomic approaches to viral discovery: We have developed genomic and bioinformatic strategies to comprehensively define the spectrum of viruses present in a given specimen or niche. These tools enable massively parallel viral diagnostics, discovery of highly divergent novel viruses, and systematic definition of the virome and its associations with health and disease.

Diseases of unknown etiology: We are currently investigating a number of diseases of unknown etiology using these methodologies. A significant effort in the laboratory is focused on diseases of the respiratory tract, the central nervous system, and the gastrointestinal tract. Although many known viruses have been implicated in these diseases, epidemiological investigations typically fail to identify an infectious agent in ~ 30% of respiratory infections, ~75% of encephalitis cases, and ~30% of cases of acute diarrhea, suggesting that novel pathogens are likely to exist. In addition we are applying these viral discovery methods to a number of other diseases, including human cancers, where viruses have been postulated to play a role in disease etiology.

Characterization of Astrovirus VA1: We discovered a novel astrovirus, astrovirus VA1, in an unexplained outbreak of gastroenteritis. Recent studies have identified astrovirus VA1 in 5 independent cases of encephalitis in immunocompromised patients. As astroviruses are traditionally associated exclusively with gastroenteritis, these finding represent a novel neurotropism and neuropathenic potential for this family of viruses. We are working to fulfill Koch’s postulates to demonstrate the causal role of astrovirus VA1 in encephalitis. Towards this end, we have developed the first cell culture system for astrovirus VA1 and we are currently establishing a small animal model of infection. In parallel, we are working to define the epidemiology and seroepidemiology of astrovirus VA1.

A C. elegans model of virus infection: We discovered Orsay virus, the first and to date only virus capable of naturally infecting the model organism C. elegans. In addition to characterizing the fundamental virology of Orsay virus, we are exploiting the robust genetic tractability of C. elegans to identify host genes that are either necessary for Orsay infection or that promote antiviral immunity. Critically, we have determined that the human orthologs of many of these genes have evolutionarily conserved function in mammals. Thus studying Orsay virus infection of C. elegans provides us with novel insights in mammalian virology and biology.