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

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

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&g...

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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
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spelling doaj-04e3a194f6354f53bab7c65eae097d7e2020-11-25T02:26:16ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672020-10-01217520752010.3390/ijms21207520The <i>Lethal(2)-Essential-for-Life</i> [<i>L(2)EFL</i>] Gene Family Modulates Dengue Virus Infection in <i>Aedes aegypti</i>Lucky R. Runtuwene0Shuichi Kawashima1Victor D. Pijoh2Josef S. B. Tuda3Kyoko Hayashida4Junya Yamagishi5Chihiro Sugimoto6Shoko Nishiyama7Michihito Sasaki8Yasuko Orba9Hirofumi Sawa10Tomohiko Takasaki11Anthony A. James12Takashi Kobayashi13Yuki Eshita14Department of Infectious Disease Control, Faculty of Medicine, Oita University, Oita 879-5593, JapanDatabase Center for Life Science, Joint Support-Center for Data Science Research, Research Organization of Information and Systems, 178-4-4 Wakashiba, Kashiwa, Chiba 277-0871, JapanFaculty of Medicine, Sam Ratulangi University, Kampus Unsrat, Bahu Manado 95-115, IndonesiaFaculty of Medicine, Sam Ratulangi University, Kampus Unsrat, Bahu Manado 95-115, IndonesiaDivision of Collaboration and Education, Research Center for Zoonosis Control, Hokkaido University, North 20, West 10 Kita-ku, Sapporo, Hokkaido 001-0020, JapanDivision of Collaboration and Education, Research Center for Zoonosis Control, Hokkaido University, North 20, West 10 Kita-ku, Sapporo, Hokkaido 001-0020, JapanDivision of Collaboration and Education, Research Center for Zoonosis Control, Hokkaido University, North 20, West 10 Kita-ku, Sapporo, Hokkaido 001-0020, JapanLaboratory of Zoonotic Diseases, Faculty of Applied Biological Sciences, Gifu University, 1-1 Yanagido, Gifu-shi, Gifu 501-1193, JapanDivision of Molecular Pathobiology, Research Center for Zoonosis Control, Hokkaido University, North 20, West 10 Kita-ku, Sapporo, Hokkaido 001-0020, JapanDivision of Molecular Pathobiology, Research Center for Zoonosis Control, Hokkaido University, North 20, West 10 Kita-ku, Sapporo, Hokkaido 001-0020, JapanDivision of Molecular Pathobiology, Research Center for Zoonosis Control, Hokkaido University, North 20, West 10 Kita-ku, Sapporo, Hokkaido 001-0020, JapanNational Institute of Infectious Diseases, Tokyo 162-8640, JapanDepartments of Microbiology & Molecular Genetics and Molecular Biology & Biochemistry, University of California, Irvine, CA 92697, USADepartment of Infectious Disease Control, Faculty of Medicine, Oita University, Oita 879-5593, JapanDepartment of Infectious Disease Control, Faculty of Medicine, Oita University, Oita 879-5593, JapanEfforts 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.https://www.mdpi.com/1422-0067/21/20/7520lethal(2)-essential-for-lifedengue<i>Aedes aegypti</i>
collection DOAJ
language English
format Article
sources DOAJ
author 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
spellingShingle 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
The <i>Lethal(2)-Essential-for-Life</i> [<i>L(2)EFL</i>] Gene Family Modulates Dengue Virus Infection in <i>Aedes aegypti</i>
International Journal of Molecular Sciences
lethal(2)-essential-for-life
dengue
<i>Aedes aegypti</i>
author_facet 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
author_sort Lucky R. Runtuwene
title The <i>Lethal(2)-Essential-for-Life</i> [<i>L(2)EFL</i>] Gene Family Modulates Dengue Virus Infection in <i>Aedes aegypti</i>
title_short The <i>Lethal(2)-Essential-for-Life</i> [<i>L(2)EFL</i>] Gene Family Modulates Dengue Virus Infection in <i>Aedes aegypti</i>
title_full The <i>Lethal(2)-Essential-for-Life</i> [<i>L(2)EFL</i>] Gene Family Modulates Dengue Virus Infection in <i>Aedes aegypti</i>
title_fullStr The <i>Lethal(2)-Essential-for-Life</i> [<i>L(2)EFL</i>] Gene Family Modulates Dengue Virus Infection in <i>Aedes aegypti</i>
title_full_unstemmed The <i>Lethal(2)-Essential-for-Life</i> [<i>L(2)EFL</i>] Gene Family Modulates Dengue Virus Infection in <i>Aedes aegypti</i>
title_sort <i>lethal(2)-essential-for-life</i> [<i>l(2)efl</i>] gene family modulates dengue virus infection in <i>aedes aegypti</i>
publisher MDPI AG
series International Journal of Molecular Sciences
issn 1661-6596
1422-0067
publishDate 2020-10-01
description 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.
topic lethal(2)-essential-for-life
dengue
<i>Aedes aegypti</i>
url https://www.mdpi.com/1422-0067/21/20/7520
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