Thi Hue Kien Duong, Edenborough Kathryn, da Silva Goncalves Daniela, Thuy Vi Tran, Casagrande Etiene, Thi Le Duyen Huynh, Thi Long Vo, Thi Dui Le, Thi Tuyet Nhu Vu, Thi Giang Nguyen, Thi Xuan Trang Huynh, Lee Elvina, Donovan-Banfield I'ah, Thi Thuy Van Huynh, Minh Nguyet Nguyen, Thanh Phong Nguyen, Van Vinh Chau Nguyen, Wills Bridget, Yacoub Sophie, Flores Heather, Simmons Cameron
World Mosquito Program, Institute of Vector-Borne Disease, Monash University, Clayton, VIC 3800, Australia.
Department of Microbiology, Biomedicine Discovery Institute, Monash University, Clayton, VIC 3800, Australia.
Virus Evol. 2023 Mar 3;9(1):vead016. doi: 10.1093/ve/vead016. eCollection 2023.
The introgression of antiviral strains of into mosquito populations is a public health intervention for the control of dengue. Plausibly, dengue virus (DENV) could evolve to bypass the antiviral effects of and undermine this approach. Here, we established a serial-passage system to investigate the evolution of DENV in mosquitoes infected with the Mel strain of . Using this system, we report on virus genetic outcomes after twenty passages of serotype 1 of DENV (DENV-1). An amino acid substitution, E203K, in the DENV-1 envelope protein was more frequently detected in the consensus sequence of virus populations passaged in Mel-infected than wild-type counterparts. Positive selection at residue 203 was reproducible; it occurred in passaged virus populations from independent DENV-1-infected patients and also in a second, independent experimental system. In wild-type mosquitoes and human cells, the 203K variant was rapidly replaced by the progenitor sequence. These findings provide proof of concept that Mel-associated selection of virus populations can occur in experimental conditions. Field-based studies are needed to explore whether Mel imparts selective pressure on DENV evolution in locations where Mel is established.
将抗病毒品系导入伊蚊种群是控制登革热的一项公共卫生干预措施。理论上，登革热病毒（DENV）可能会进化以绕过该抗病毒品系的抗病毒作用并破坏这种方法。在此，我们建立了一个连续传代系统，以研究DENV在感染了Mel品系的伊蚊中的进化情况。利用这个系统，我们报告了DENV血清型1（DENV-1）经过二十代传代后的病毒基因结果。在感染Mel的伊蚊中传代的病毒群体的共有序列中，比野生型对应物更频繁地检测到DENV-1包膜蛋白中的一个氨基酸取代，即E203K。在第203位残基处的正选择是可重复的；它发生在来自独立的DENV-1感染患者的传代病毒群体中，也发生在第二个独立的实验系统中。在野生型伊蚊和人类细胞中，203K变体迅速被祖系序列取代。这些发现提供了概念验证，即Mel相关的病毒群体选择可以在实验条件下发生。需要进行基于现场的研究，以探索在Mel已建立的地区，Mel是否会对DENV的进化施加选择压力。
