Department of Biology, New Mexico State University, Las Cruces, NM 88003, USA.
Department of Pathology, The University of Texas Medical Branch, Galveston, TX 77555-0609, USA.
Viruses. 2019 Nov 18;11(11):1072. doi: 10.3390/v11111072.
Evolutionary theory indicates that virus virulence is shaped by a trade-off between instantaneous rate of transmission and duration of infection. For most viruses, infection is curtailed by immune clearance, but there are few empirical tests of the transmission-clearance trade-off hypothesis. We exposed A129 mice to bites from groups of 1, 2-4, or 6-9 mosquitoes infected with Zika virus (ZIKV). We predicted that a higher number of infectious mosquito bites would deliver a higher total dose of the virus, and that increasing dose would result in earlier onset, higher magnitude, and shorter duration of viremia, as well as a more robust neutralizing antibody response. We found that increases in the number of mosquito bites delivered resulted in significantly different virus replication dynamics with higher, earlier peak titers. All mice experienced a transient weight loss following infection, but the nadir in weight loss was delayed in the mice that received the highest number of bites. Viremia persisted past the period of measurement in this study, so we did not capture its duration. However, the association at the level of the individual mouse between the estimated virus dose delivered and neutralizing antibody titer was remarkably strong, supporting the transmission-clearance trade-off hypothesis.
进化理论表明，病毒的毒力是由瞬时传播率和感染持续时间之间的权衡决定的。对于大多数病毒来说，感染会被免疫清除所抑制，但对传播-清除权衡假说的实证检验很少。我们让 A129 小鼠被感染寨卡病毒（ZIKV）的 1、2-4 或 6-9 只蚊子叮咬。我们预测，更多数量的传染性蚊子叮咬会传递更高的病毒总剂量，而增加剂量会导致病毒血症更早出现、更严重、持续时间更短，以及更强烈的中和抗体反应。我们发现，随着蚊子叮咬次数的增加，病毒复制动力学发生了显著变化，病毒滴度更高，出现得更早。所有感染的小鼠体重都出现了短暂下降，但接受最高叮咬数的小鼠体重下降的最低点延迟了。病毒血症持续时间超过了本研究的测量时间，因此我们无法捕捉到其持续时间。然而，个体小鼠之间在传递的病毒剂量和中和抗体滴度之间的关联非常显著，支持了传播-清除权衡假说。
