Tang Biao, Xiao Yanni, Sander Beate, Kulkarni Manisha A, Wu Jianhong
Laboratory for Industrial and Applied Mathematics (LIAM), York University, Toronto, Canada.
Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, Canada.
R Soc Open Sci. 2020 Apr 15;7(4):191749. doi: 10.1098/rsos.191749. eCollection 2020 Apr.
Human infections with viruses of the genus , including dengue virus (DENV) and Zika virus (ZIKV), are of increasing global importance. Owing to antibody-dependent enhancement (ADE), secondary infection with one following primary infection with another can result in a significantly larger peak viral load with a much higher risk of severe disease. Although several mathematical models have been developed to quantify the virus dynamics in the primary and secondary infections of DENV, little progress has been made regarding secondary infection of DENV after a primary infection of ZIKV, or DENV-ZIKV co-infection. Here, we address this critical gap by developing compartmental models of virus dynamics. We first fitted the models to published data on dengue viral loads of the primary and secondary infections with the observation that the primary infection reaches its peak much more gradually than the secondary infection. We then quantitatively show that ADE is the key factor determining a sharp increase/decrease of viral load near the peak time in the secondary infection. In comparison, our simulations of DENV and ZIKV co-infection (simultaneous rather than sequential) show that ADE has very limited influence on the peak DENV viral load. This indicates pre-existing immunity to ZIKV is the determinant of a high level of ADE effect. Our numerical simulations show that (i) in the absence of ADE effect, a subsequent co-infection is beneficial to the second virus; and (ii) if ADE is feasible, then a subsequent co-infection can induce greater damage to the host with a higher peak viral load and a much earlier peak time for the second virus, and for the second peak for the first virus.
人类感染包括登革热病毒（DENV）和寨卡病毒（ZIKV）在内的该属病毒，在全球范围内的重要性日益增加。由于抗体依赖增强（ADE）作用，在初次感染一种病毒后再感染另一种病毒，可能会导致病毒载量峰值显著增大，且患重病的风险更高。尽管已经开发了几种数学模型来量化登革热病毒初次和二次感染中的病毒动态，但在寨卡病毒初次感染后登革热病毒的二次感染或登革热病毒与寨卡病毒共感染方面进展甚微。在此，我们通过开发病毒动态的房室模型来填补这一关键空白。我们首先将模型拟合到已发表的关于登革热病毒初次和二次感染病毒载量的数据，观察到初次感染达到峰值的过程比二次感染更为缓慢。然后我们定量表明，ADE是决定二次感染峰值时间附近病毒载量急剧增减的关键因素。相比之下，我们对登革热病毒和寨卡病毒共感染（同时而非相继感染）的模拟表明，ADE对登革热病毒载量峰值的影响非常有限。这表明对寨卡病毒的预先存在的免疫力是高水平ADE效应的决定因素。我们的数值模拟表明：（i）在没有ADE效应的情况下，随后的共感染对第二种病毒有益；（ii）如果ADE可行，那么随后的共感染会对宿主造成更大损害，第二种病毒的病毒载量峰值更高，且峰值时间更早，第一种病毒的第二个峰值也是如此。
