Division of Infectious Diseases and Vaccinology, School of Public Health, University of California, Berkeley, 185 Li Ka Shing Center, 1951 Oxford Street, Berkeley, CA 94720-3370, USA.
Laboratorio Nacional de Virología, Centro Nacional de Diagnóstico y Referencia, Ministry of Health, Managua 16064, Nicaragua.
Cell Host Microbe. 2017 Sep 13;22(3):400-410.e5. doi: 10.1016/j.chom.2017.08.003.
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.
登革热是由四种登革病毒血清型（DENV-1 至 DENV-4）引起的，在人类中是一种高度流行的蚊媒病毒性疾病。然而，驱动登革病毒在人体宿主（宿主内）内微进化的选择压力仍然未知。我们采用全基因组分段扩增方法结合深度测序，对来自 77 名登革热患者的外周血单核细胞（PBMC）和血浆样本中的 DENV-3 宿主内多样性进行了分析。DENV-3 宿主内多样性似乎是由免疫压力以及 PBMC 中的复制成功以及其他潜在复制部位驱动的。在 59%-78%的患者中，病毒包膜和前膜/膜蛋白中检测到宿主内变异的热点，这些蛋白共同构成了病毒粒子的表面。热点处的优势变异体通过趋同微进化产生，似乎是免疫逃逸变异体，并且由于病毒复制缺陷，在宏观水平上受到进化限制。因此，登革热是一种急性感染的例子，在这种感染中，个体感染的选择压力会驱动病毒的快速宿主内微进化。
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