4.6 Article

Infection Kinetics and Transmissibility of a Reanimated Dengue Virus Serotype 4 Identified Originally in Wild Aedes aegypti From Florida

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FRONTIERS IN MICROBIOLOGY
卷 12, 期 -, 页码 -

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FRONTIERS MEDIA SA
DOI: 10.3389/fmicb.2021.734903

关键词

Aedes aegypti; mosquito; infectious clone; arbovirus; dengue virus serotype 4; transovarial transmission; vertical transmission; Florida

资金

  1. United States Centers for Disease Control (CDC) [1U01CK000510-03]
  2. University of Florida Emerging Pathogens Institute
  3. University of Florida Preeminence Initiative
  4. NIH [T32 AI 007110, AI142759, AI134907, AI145617, UL1TR001439]
  5. CDC grant for the Western Gulf Center of Excellence for Vector-Borne Diseases
  6. Sealy Smith Foundation
  7. Kleberg Foundation
  8. John S. Dunn Foundation
  9. Amon G. Carter Foundation
  10. Gilson Longenbaugh Foundation
  11. Summerfield Robert Foundation
  12. U.S. Navy

向作者/读者索取更多资源

Dengue virus, primarily transmitted by Aedes aegypti mosquitoes, has been increasing in autochthonous cases in Florida since 2009, alongside consistent importation cases. Studies reveal the potential for undetected human-mosquito transmission and long-term maintenance of the virus in mosquito populations.
Dengue virus is the most prevalent mosquito-borne virus, causing approximately 390 million infections and 25,000 deaths per year. Aedes aegypti, the primary mosquito vector of dengue virus, is well-established throughout the state of Florida, United States. Autochthonous transmission of dengue virus to humans in Florida has been increasing since 2009, alongside consistent importation of dengue cases. However, most cases of first infection with dengue are asymptomatic and the virus can be maintained in mosquito populations, complicating surveillance and leading to an underestimation of disease risk. Metagenomic sequencing of A. aegypti mosquitoes in Manatee County, Florida revealed the presence of dengue virus serotype 4 (DENV-4) genomes in mosquitoes from multiple trapping sites over 2years, in the absence of a human DENV-4 index case, and even though a locally acquired case of DENV-4 has never been reported in Florida. This finding suggested that: (i) DENV-4 may circulate among humans undetected; (ii) the virus was being maintained in the mosquito population, or (iii) the detected complete genome sequence may not represent a viable virus. This study demonstrates that an infectious clone generated from the Manatee County DENV-4 (DENV-4M) sequence is capable of infecting mammalian and insect tissue culture systems, as well as adult female A. aegypti mosquitoes when fed in a blood meal. However, the virus is subject to a dose dependent infection barrier in mosquitoes, and has a kinetic delay compared to a phylogenetically related wild-type (WT) control virus from a symptomatic child, DENV-4H (strain Homo sapiens/Haiti-0075/2015, GenBank accession MK514144.1). DENV-4M disseminates from the midgut to the ovary and saliva at 14days post-infection. Viral RNA was also detectable in the adult female offspring of DENV-4M infected mosquitoes. These results demonstrate that the virus is capable of infecting vector mosquitoes, is transmissible by bite, and is vertically transmitted, indicating a mechanism for maintenance in the environment without human-mosquito transmission. These findings suggest undetected human-mosquito transmission and/or long-term maintenance of the virus in the mosquito population is occurring in Florida, and underscore the importance of proactive surveillance for viruses in mosquitoes.

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