Abstract
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.
Highlights
Rates of dengue virus (DENV) infection have shown a marked increase during the last two decades, imposing a sizable burden on the health systems and economies of affected LatinAmerican countries [1]
We examine the influence of viral mutation rate, timescale, and the effect of vertical transmission on probability of novel serotype emergence
The results of our analysis unexpectedly suggest that the peri-urban environment is a major site of viral evolution and that vertical transmission has little influence on the probability of novel serotype emergence
Summary
Rates of dengue virus (DENV) infection have shown a marked increase during the last two decades, imposing a sizable burden on the health systems and economies of affected LatinAmerican countries [1]. Part of the difficulty for dengue vaccine design arises from the existence of 4 distinct dengue virus serotypes, each with multiple genomic sequences. Despite the existence of thousands of genotypes for each serotype, the viruses maintain high homology between their structural protein sequences [3]. This phenomenon contrasts with human papillomavirus (a DNA virus), where observed mutations have given rise to over 170 serotypes [4]. The occurrence of DENV viruses not belonging to the 4 previously described serotypes has been reported in Malaysia, but this newcomer virus did not further propagate in the population [5].
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