PRJNA227457
Comparative Genomics of Respiratory Syncytial Virus for Broad Institute Viral Genomics Initiative
We propose to evaluate RSV sequence diversity and the effects of immune pressure on viral molecular evolution through deep sequencing over the course of infection in immunocompetent and immunocompromised hosts. To do so, we have obtained collections of upper airway samples from individuals of varying immune status with RSV infection. These include multiple samples from a single infant with Severe Combined Immune Deficiency Syndrome (SCID) who had persistent RSV infection continuing over several months before and after institution of an effective immune response, samples from multiple experimentally infected healthy adults, all inoculated with the same wild-type virus, and samples from multiple previously healthy RSV infected infants who had been naturally infected with RSV. Quantitative RSV load has been obtained from parallel aliquots of all of these samples, and clinical parameters have been characterized in association with each time point. These studies will provide the first comprehensive view of viral evolutionary dynamics during individual infections, and comparisons among the datasets derived from individuals with varying immune states will provide insight into the interaction between host immune function and viral evolution. Furthermore, this approach will lay the groundwork with which to investigate the evolutionary dynamics of other acute viral infections.