Impact of Intrahost Diversity on DSS

Justification/Summary

Understanding the dynamics of intrahost genomic diversity remains a critical need in the study of flaviviruses such as dengue and west nile. RNA viruses exhibit a high degree of sequence variation not just between isolates, but also among viruses within an individual. This in part is due to the viral RNA polymerase and its inability to proofread. As a result, viral infections within an individual exist as a population of closely related sequences that are called quasispecies. The role of quasispecies in disease pathogenesis, transmission, and viral evolution is suspected to be important for RNA viruses. At a recent meeting of GRID at the Broad such work was identified as an important priority, and it was discussed that the existing intrahost efforts underway in the dengue genome project be extended.

A unique opportunity exists to capitalize on a recent study in the laboratory of Dr. Cameron Simmons. Dr. Simmons and his group have a set of 20 patients with well characterized disease outcomes (i.e. DF, DHF, and DSS) and for which viral viremias were assayed during the course of infection. The patients are stratified by disease outcome and whether they have a primary or secondary infection. The viremia results are extremely interesting in that there is a clear difference in the viremia dynamics between primary and secondary patients and between DF and DHF patients. The genomic make up of the viral population is almost certainly driving this important finding and these samples provide a unique opportunity to understand how intrahost diversity drives viremia and disease in dengue.

People

Principal External Collaborator

Cameron Simmons - Oxford University Clinical Research Unit, Hospital for Tropical Diseases, Ho Chi Minh City, VietNam

Funding

Funding for this sequencing project was provided by the National Institute of Allergy and Infectious Diseases.

Cohort Description

FR - The FR study is a multicentre descriptive study of early Dengue in adults in 4 hospitals in southern Viet Nam. The aim of the study is to identify clinical, host genetic, viral, and immunological risk factors for Dengue shock syndrome in adult patients enrolled within 72 hours of fever onset.