When interference is beneficial
Small hairpin RNA (shRNA) can silence target gene expression via short interfering RNA (siRNA). Use of RNAi has led to the development of siRNA screens that can identify viral genes crucial to infection. One good example is identifying new host genes that impact RNA-virus replication. The VIRUSSHCREEN (Discovery of novel aspects of host-pathogen interactions through the use of powerful genome-wide shRNA libraries) project geared their research toward the infection cycle of human herpes virus. They focused their investigations on endoplasmic reticulum-associated degradation that is linked to viral infection, a stress response phenomenon. Two genome wide shRNA libraries were constructed and genome-wide library screens performed. Results revealed many human genes involved in trafficking of the deadly toxin ricin as well as the movement of biomolecules in human cells. Study of action of US11, the protein that is responsible for immune system evasion of herpes revealed key players in the avoidance process. One of these, a new E3 ubiquitin ligase, is linked to action of US11. Another has a role in breaking down cellular targets unrelated to virus infection. Screens and screening tools developed in VIRUSSHCREEN can be applied widely in genome-wide research. Exploration of virus-host interactions could be exploited to develop new antiviral therapies.
Keywords
Gene silencing, small hairpin RNA, siRNA, RNAi, herpes, virus-host interactions
