Abstract
Dengue virus (DENV) causes dengue fever and severe hemorrhagic fever in humans and is primarily transmitted by Aedes aegypti and A. albopictus mosquitoes. The incidence of DENV infection has been gradually increasing in recent years due to global urbanization and international travel. Understanding the virulence determinants in host and vector transmissibility of emerging epidemic DENV will be critical to combat potential outbreaks. The DENV serotype 2 (DENV-2), which caused a widespread outbreak in Taiwan in 2015 (TW2015), is of the Cosmopolitan genotype and is phylogenetically related to the virus strain linked to another large outbreak in Indonesia in 2015. We found that the TW2015 virus was highly virulent in type I and type II interferon-deficient mice, with robust replication in spleen, lung, and intestine. The TW2015 virus also had high transmissibility to Aedes mosquitoes and could be effectively spread in a continuous mosquitoes-mouse-mosquitoes-mouse transmission cycle. By making 16681-based mutants carrying different segments of the TW2015 virus, we identified the structural pre-membrane (prM) and envelope (E) genes as key virulence determinants in the host, with involvement in the high transmissibility of the TW2015 virus in mosquitoes. The transmission mouse model will make a useful platform for evaluation of DENV with high epidemic potential and development of new strategies against dengue outbreaks.
Highlights
The dengue virus (DENV) belongs to the Flavivirus genus, which includes several other arthropod-borne viruses, such as the Zika, West Nile, and yellow fever viruses
Dengue fever and dengue hemorrhagic fever in humans are caused by Aedes mosquitomediated dengue virus infection
Large dengue outbreaks occurred in recent years and many tropical and subtropical countries became hyperendemic with all four dengue virus serotypes
Summary
The dengue virus (DENV) belongs to the Flavivirus genus, which includes several other arthropod-borne viruses, such as the Zika, West Nile, and yellow fever viruses. All flaviviruses have a single-stranded, positive-sense RNA genome and an outer viral envelope. The DENV RNA genome encodes a large polyprotein (C-prM-E-NS1-NS2A-NS2B-NS3-NS4A-NS4B-NS5) that is further processed into ten mature proteins by host and viral proteases. An estimated 390 million cases of dengue infection occur every year[1]. From 2000 through 2013, many countries in the tropics and subtropics became hyperendemic with all four DENV serotypes co-circulating in those regions[2]. Global urbanization and international travel may be major contributors to the geographic expansion of DENV and its mosquito vectors in tropical regions[2,3]
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