Mobile Genetic Elements
Approximately 50% of the human genome is comprised of repetitive elements. By far, the largest fraction of repetitive DNA is contributed by transposons (45% of the genome). While in healthy somatic cells transposon expression is typically silenced, under conditions of stress, such as viral infection, transposon expression is robustly induced. We previously demonstrated that Short Interspersed Nuclear Elements (SINEs), a family of transposons that occupy ~10 of the mammalian genome, our robustly induced during gammaherpesviral infection and stimulate the activation of the cell-intrinsic innate immune system. We are continuing this work by addressing the role of other transposon families in gammaherpesviral pathogenesis.
Viral Noncoding RNAs
It has become increasingly apparent that viruses, much like the cells they infect, utilize noncoding RNAs in their gene regulatory systems. In fact, many of the species of noncoding RNA that are encoded in the human genome can also be found in viruses, including transfer RNAs (tRNA), small nucleolar RNAs (snoRNAs), microRNAs (miRNAs), and long noncoding RNAs (lncRNAs); γHVs produce all of these, and in many cases their functional relevance to pathogenesis is unknown. We are employing novel biochemical purification and sequencing strategies aimed at characterizing γHV noncoding RNAs and their role in pathogenesis. These studies are revealing unanticipated roles for viral-derived noncoding RNAs in the regulation of gene expression.
Given γHVs establish life-long infections, these viruses are highly dependent on efficient immune evasion strategies. Uncovering strategies γHVs employ to suppress and/or commandeer the immune response are vital to developing strategies to combat γHV infections. We are currently performing genome-wide screens directed at dissecting the immune response during γHV infection and validating hits in relevant infection models.