![]() ![]() Risk factors that contribute to dengue severity include preexisting immunity and viral genetics ( 6), as well as host genetic factors. DENV now causes an estimated 390 million annual human infections worldwide ( 3), a quarter of which manifest as an acute, debilitating fever (dengue fever) that can progress to life-threatening manifestations with vascular leak (dengue hemorrhagic fever and dengue shock syndrome) ( 4), severe bleeding, and/or organ damage, collectively known as severe dengue ( 5). However, due to a complex combination of factors that include migration, globalization, and climate change ( 1, 2), considerable expansion in the habitat range of the mosquito vectors that transmit DENV and in the geographic reach and number of dengue epidemics has recently occurred. albopictus mosquitoes, which are typically found in tropical and subtropical regions of the world. DENV is transmitted by Aedes aegypti and A. These findings provide insight into vector-driven evolution of DENV epidemics.ĭengue virus (DENV) is an arbovirus of global importance comprised of four phylogenetically related serotypes, DENV serotype 1 (DENV-1) to DENV-4. Here, we investigate the replicative fitness of two clades of DENV serotype 2 in Aedes aegypti cells and mosquitoes collected from the region where the viruses circulated and conclude that increased replicative fitness could have contributed to a DENV clade replacement event in Nicaragua. What drives the frequent replacement of a previously circulating DENV clade by another is unclear. DENV consists of four serotypes, in turn composed of genotypes and genetically distinct clades. This is due to globalization, unplanned urbanization, and climate change, as well as host genetics and immune responses and viral genetic changes. Dengue epidemics continue to increase in frequency, geographic range, and severity and are a major public health concern. albopictus mosquitoes in tropical and subtropical regions worldwide. IMPORTANCE Dengue virus (DENV), one of the most medically important arthropod-borne viruses, is transmitted to humans by Aedes aegypti and A. aegypti, suggests a shorter extrinsic incubation period for NI-2B viruses, which could have contributed to the clade replacement event in Managua. This early fitness advantage of NI-2B viruses over NI-1 viruses in the native vector, A. Taken together, these data demonstrate that clade NI-2B holds a replicative advantage over clade NI-1 early in infection that wanes at later time points. We also found that the percentage of mosquitoes in which NI-2B viruses were dominant was significantly higher than that in which NI-1 viruses were dominant on day 7 but not at later time points. At 7 dpi, NI-2B viruses displayed a significantly higher replicative index in legs and salivary glands however, this advantage was lost by 14 and 21 dpi. Results consistently showed a significant replicative advantage of NI-2B over NI-1 viruses early after infection in vitro, and in mosquitoes, NI-2B viruses attained a higher replicative index than NI-1 isolates 3 to 7 days postinfection (dpi). In coinfection experiments, several different pairs of NI-1 and NI-2B clinical isolates were used to infect Aag2 cells or blood-fed A. aegypti mosquitoes reared from eggs collected in Managua. Here, we describe our studies of the replicative ability of NI-1 and NI-2B viruses in an A. We previously reported a clade replacement of the DENV-2 Asian-American genotype NI-1 clade by the NI-2B clade in Managua, Nicaragua. ![]() albopictus mosquitoes, causing up to 390 million DENV infections worldwide each year. The four dengue virus (DENV) serotypes (DENV serotype 1 to DENV-4) are transmitted by Aedes aegypti and A. ![]()
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