The <i>Lethal(2)-Essential-for-Life</i> [<i>L(2)EFL</i>] Gene Family Modulates Dengue Virus Infection in <i>Aedes aegypti</i>

• Main Authors: Lucky R. Runtuwene, Shuichi Kawashima, Victor D. Pijoh, Josef S. B. Tuda, Kyoko Hayashida, Junya Yamagishi, Chihiro Sugimoto, Shoko Nishiyama, Michihito Sasaki, Yasuko Orba, Hirofumi Sawa, Tomohiko Takasaki, Anthony A. James, Takashi Kobayashi, Yuki Eshita
• Format: Article
• Language: English
• Published: MDPI AG 2020-10-01
• Series: International Journal of Molecular Sciences
• Subjects: lethal(2)-essential-for-life; dengue; <i>Aedes aegypti</i>
• Online Access: https://www.mdpi.com/1422-0067/21/20/7520
• ISSN: 1661-6596; 1422-0067

Efforts to determine the mosquito genes that affect dengue virus replication have identified a number of candidates that positively or negatively modify amplification in the invertebrate host. We used deep sequencing to compare the differential transcript abundances in <i>Aedes aegypti</i> 14 days post dengue infection to those of uninfected <i>Ae. aegypti</i>. The gene <i>lethal(2)-essential-for-life</i> [<i>l(2)efl</i>], which encodes a member of the heat shock 20 protein (HSP20) family, was upregulated following dengue virus type 2 (DENV-2) infection in vivo. The transcripts of this gene did not exhibit differential accumulation in mosquitoes exposed to insecticides or pollutants. The induction and overexpression of <i>l(2)efl</i> gene products using poly(I:C) resulted in decreased DENV-2 replication in the cell line. In contrast, the RNAi-mediated suppression of <i>l(2)efl</i> gene products resulted in enhanced DENV-2 replication, but this enhancement occurred only if multiple <i>l(2)efl</i> genes were suppressed. <i>l(2)efl</i> homologs induce the phosphorylation of eukaryotic initiation factor 2α (eIF2α) in the fruit fly <i>Drosophila melanogaster</i>, and we confirmed this finding in the cell line. However, the mechanism by which <i>l(2)efl</i> phosphorylates eIF2α remains unclear. We conclude that <i>l(2)efl</i> encodes a potential anti-dengue protein in the vector mosquito.