Intrahost Selection Pressures Drive Rapid Dengue Virus Microevolution in Acute Human Infections

Publication date: 13 September 2017
Source:Cell Host & Microbe, Volume 22, Issue 3
Author(s): Poornima Parameswaran, Chunling Wang, Surbhi Bharat Trivedi, Meghana Eswarappa, Magelda Montoya, Angel Balmaseda, Eva Harris
Dengue, caused by four dengue virus serotypes (DENV-1 to DENV-4), is a highly prevalent mosquito-borne viral disease in humans. Yet, selection pressures driving DENV microevolution within human hosts (intrahost) remain unknown. We employed a whole-genome segmented amplification approach coupled with deep sequencing to profile DENV-3 intrahost diversity in peripheral blood mononuclear cell (PBMC) and plasma samples from 77 dengue patients. DENV-3 intrahost diversity appears to be driven by immune pressures as well as replicative success in PBMCs and potentially other replication sites. Hotspots for intrahost variation were detected in 59%–78% of patients in the viral Envelope and pre-Membrane/Membrane proteins, which together form the virion surface. Dominant variants at the hotspots arose via convergent microevolution, appear to be immune-escape variants, and were evolutionarily constrained at the macro level due to viral replication defects. Dengue is thus an example of an acute infection in which selection pressures within infected individuals drive rapid intrahost virus microevolution.

Graphical abstract

Teaser

Dengue, caused by DENV-1 to -4, is a highly prevalent viral disease. Parameswaran et al. profile DENV-3 intrahost diversity in 77 patients, showing that intrahost virus microevolution occurs in PBMCs and potentially other replication sites. They find that intrahost variants, likely immune-escape hotspots, arise via convergent microevolution, yet are evolutionarily constrained by replication defects.


http://ift.tt/2f812vA