Respiratory syncytial virus (RSV) is the major cause of hospitalization of infants. It is also a significant cause of disease in the elderly and immunocompromised. As yet, there is no vaccine or effective antiviral treatment to control the virus. RSV has an RNA genome, which is transcribed to produce capped and polyadenylated mRNAs, and replicated to generate progeny genomes. RSV transcription and genome replication are both performed by a multi-functional viral RNA dependent RNA polymerase. In this presentation, I will provide an overview of the mechanisms underlying RSV transcription and genome replication, and then describe work performed with small molecule polymerase inhibitors, coupled with amino acid substitution analysis of the large polymerase subunit (L). This work sheds some light on the structure-function relationships of the polymerase as it performs its various activities.
Who is Rachel Fearns?
- Associate Professor, Dept. of Microbiology, Boston University School of Medicine.
- Faculty member, National Emerging Infectious Disease Laboratories, Boston University.
I have spent the last twenty-one years researching the transcription/ replication mechanisms of a non-segmented negative strand RNA virus, respiratory syncytial virus (RSV). During my post-doctoral training at the Division of Intramural Research at the National Institute of Allergy and Infectious Diseases I investigated the role of trans-acting RSV proteins and cis-acting RNA sequences in RSV transcription and replication. During my time as a principal investigator my research group has performed extensive analysis of the signal sequences within the RSV promoter regions and the events that occur when the polymerase interacts with them. My group has developed cell-based assays that allow different events in RSV transcription and RNA replication to be dissected, and we have expertise in generating and analyzing mutant recombinant versions of infectious RSV. In work published in 2012, we showed for the first time that it was possible to purify active RSV polymerase complexes, a breakthrough that allowed us to develop an assay in which RSV RNA synthesis is reconstituted in vitro using purified protein and RNA oligonucleotide templates. Because of my group’s unique expertise studying RSV transcription and replication mechanisms, several pharmaceutical companies have sought our collaborative support. In more recent work, my group has begun to extend the techniques we have developed to other related viruses and to identify similarities and differences in transcription and replication mechanisms within the non-segmented negative strand RNA viruses.
Ansprechpartner: Prof. Dr. Thomas Pietschmann
- Fearns_poster_Seminar_vertikal.pdf396 K