When new viral diseases appear, they attract a lot of attention – think of AIDS, SARS, West Nile Fever, or Avian flu. Because of high-profile outbreaks like these, we tend to assume that every virus bodes ill for humankind. Yet, viruses have been with us for hundreds of millions of years, and they are everywhere: a milliliter of seawater can contain several million viruses, the bacteria that live in our guts are infected with their own viruses, our pets, our plants, even our food contain viruses. In other words, viruses have been a major evolutionary force throughout the history of life, and we are continuously exposed to them in our daily lives. Most of these exposures don’t result in infections, and even those that do often fail to spread or cause significant disease. So, why do viruses occasionally succeed in jumping from one species to another (like HIV in humans), sparking outbreaks and epidemics, yet at other times remain mostly confined to their natural hosts? To find the answers, we need to look at how viruses and their hosts interact at the genetic level. In our laboratory, we take our cues from evolutionary biology, with an emphasis on understanding how viruses have driven evolution of host genes, and at the same time, asking how our molecular defenses influence evolution of the viruses that surround and infect us. By taking this perspective, we can identify specific molecular interactions that have been fine tuned by millions of years of virus-host co-evolution, using nature as our guide in the search to better understand viruses and the molecular mechanisms of infectious disease.
Rather than focus on a single viral agent or model system, projects in the laboratory are usually based on comparative approaches, examining each virus-host interaction in the context of related viruses and their hosts. For example, a major focus of the lab is on the primate lentiviruses, including HIV-1 and its cousins, the simian immunodeficiency viruses (SIV) of old world primates. Our work in this area involves direct comparisons of HIV and different SIV isolates, and parallel examination of how each has evolved unique molecular interactions with the cells of its respective host. We also look into the past to understand how retroviruses and their hosts have co-evolved over thousands of generations, by studying endogenous retroviruses (ERVs). ERV are “fossils” sequences left behind in our genomes in the wake of ancient retroviral epidemics (forerunners of the modern AIDS epidemic), and like real fossils, ERV can be used to infer past history. Finally, recent projects in the lab broaden our examination of virus-host interactions beyond retroviruses, to include DNA viruses (e.g., poxviruses) and RNA viruses (e.g., Totiviruses of unicellular parasites and fungi).
More details can be found under research or by reading recent publications from our lab. For those with a general interest in viruses, check out Vincent Racaniello’s This Week In Virology podcast, or the American Society for Microbiology’s Small Things Considered blog.