Open AccessAggressive organ penetration and high vector transmissibility of epidemic dengue virus-2 Cosmopolitan genotype in a transmission mouse model
Author(s) -
Jhe-Jhih Lin,
Pei-Jung Chung,
Shih-Syong Dai,
Wan-Ting Tsai,
YuFeng Lin,
Yi-Ping Kuo,
Kuen-Nan Tsai,
Chia-Hao Chien,
De-Jiun Tsai,
Ming-Sian Wu,
Pei-Yun Shu,
Andrew Yueh,
HsinWei Chen,
Chunhong Chen,
Guann-Yi Yu
Publication year - 2021
Publication title -
plos pathogens
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.719
H-Index - 206
eISSN - 1553-7374
pISSN - 1553-7366
DOI - 10.1371/journal.ppat.1009480
Subject(s) - virology , dengue virus , biology , dengue fever , outbreak , aedes aegypti , virus , aedes albopictus , virulence , transmissibility (structural dynamics) , vector (molecular biology) , transmission (telecommunications) , gene , genetics , physics , engineering , vibration isolation , quantum mechanics , larva , electrical engineering , vibration , recombinant dna , botany
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.