Centro de Investigación Sobre Enfermedades Infecciosas, Instituto Nacional de Salud Pública, Cuernavaca, Morelos, México.
ZYUS Life Sciences Inc., Saskatoon, Saskatchewan, Canada.
PLoS One. 2021 Apr 5;16(4):e0248765. doi: 10.1371/journal.pone.0248765. eCollection 2021.
Since their first sequencing 40 years ago, Dengue virus (DENV) genotypes have shown extreme coherence regarding the serotype class they encode. Considering that DENV is a ribonucleic acid (RNA) virus with a high mutation rate, this behavior is intriguing. Here, we explore the effect of various parameters on likelihood of new serotype emergence. In order to determine the time scales of such an event, we used a Timed Markov Transmission Model to explore the influences of sylvatic versus peri-urban transmission, viral mutation rate, and vertical transmission on the probabilities of novel serotype emergence. We found that around 1 000 years are required for a new serotype to emerge, consistent with phylogenetic analysis of extant dengue serotypes. Furthermore, we show that likelihood of establishing chains of mosquito-human-mosquito infection, known as consolidation, is the primary factor which constrains novel serotype emergence. Our work illustrates the restrictions on and provides a mechanistic explanation for the low probability of novel dengue virus serotype emergence and the low number of observed DENV serotypes.
自 40 年前首次测序以来，登革热病毒（DENV）基因型在其所编码的血清型类别方面表现出极高的一致性。考虑到 DENV 是一种具有高突变率的核糖核酸（RNA）病毒，这种行为令人费解。在这里，我们探讨了各种参数对新血清型出现可能性的影响。为了确定这种事件的时间尺度，我们使用时间标记传播模型来探讨森林型与城市周边型传播、病毒突变率和垂直传播对新型血清型出现概率的影响。我们发现，大约需要 1000 年才能出现新的血清型，这与现有的登革热血清型的系统发育分析一致。此外，我们还表明，建立蚊子-人类-蚊子感染链的可能性，即巩固，是限制新型血清型出现的主要因素。我们的工作说明了限制新登革热病毒血清型出现的可能性以及观察到的 DENV 血清型数量较少的原因，并提供了一种机制解释。
