Mosquito cellular factors and functions in mediating the infectious entry of chikungunya virus.
Chikungunya virus (CHIKV) is an arthropod-borne virus responsible for recent epidemics in the Asia Pacific regions. A customized gene expression microarray of 18,760 transcripts known to target Aedes mosquito genome was used to identify host genes that are differentially regulated during the infecti...
Published in: | PLoS Neglected Tropical Diseases |
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ftdoajarticles:oai:doaj.org/article:dc5475e9afd047609fe4e783129565be 2023-05-15T15:12:52+02:00 Mosquito cellular factors and functions in mediating the infectious entry of chikungunya virus. Regina Ching Hua Lee Hapuarachchige Chanditha Hapuarachchi Karen Caiyun Chen Khairunnisa' Mohamed Hussain Huixin Chen Swee Ling Low Lee Ching Ng Raymond Lin Mary Mah-Lee Ng Justin Jang Hann Chu 2013-01-01T00:00:00Z https://doi.org/10.1371/journal.pntd.0002050 https://doaj.org/article/dc5475e9afd047609fe4e783129565be EN eng Public Library of Science (PLoS) http://europepmc.org/articles/PMC3567007?pdf=render https://doaj.org/toc/1935-2735 1935-2735 doi:10.1371/journal.pntd.0002050 https://doaj.org/article/dc5475e9afd047609fe4e783129565be PLoS Neglected Tropical Diseases, Vol 7, Iss 2, p e2050 (2013) Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 article 2013 ftdoajarticles https://doi.org/10.1371/journal.pntd.0002050 2022-12-31T13:20:55Z Chikungunya virus (CHIKV) is an arthropod-borne virus responsible for recent epidemics in the Asia Pacific regions. A customized gene expression microarray of 18,760 transcripts known to target Aedes mosquito genome was used to identify host genes that are differentially regulated during the infectious entry process of CHIKV infection on C6/36 mosquito cells. Several genes such as epsin I (EPN1), epidermal growth factor receptor pathway substrate 15 (EPS15) and Huntingtin interacting protein I (HIP1) were identified to be differentially expressed during CHIKV infection and known to be involved in clathrin-mediated endocytosis (CME). Transmission electron microscopy analyses further revealed the presence of CHIKV particles within invaginations of the plasma membrane, resembling clathrin-coated pits. Characterization of vesicles involved in the endocytic trafficking processes of CHIKV revealed the translocation of the virus particles to the early endosomes and subsequently to the late endosomes and lysosomes. Treatment with receptor-mediated endocytosis inhibitor, monodansylcadaverine and clathrin-associated drug inhibitors, chlorpromazine and dynasore inhibited CHIKV entry, whereas no inhibition was observed with caveolin-related drug inhibitors. Inhibition of CHIKV entry upon treatment with low-endosomal pH inhibitors indicated that low pH is essential for viral entry processes. CHIKV entry by clathrin-mediated endocytosis was validated via overexpression of a dominant-negative mutant of Eps15, in which infectious entry was reduced, while siRNA-based knockdown of genes associated with CME, low endosomal pH and RAB trafficking proteins exhibited significant levels of CHIKV inhibition. This study revealed, for the first time, that the infectious entry of CHIKV into mosquito cells is mediated by the clathrin-dependent endocytic pathway. Article in Journal/Newspaper Arctic Directory of Open Access Journals: DOAJ Articles Arctic Pacific PLoS Neglected Tropical Diseases 7 2 e2050 |
institution |
Open Polar |
collection |
Directory of Open Access Journals: DOAJ Articles |
op_collection_id |
ftdoajarticles |
language |
English |
topic |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
spellingShingle |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 Regina Ching Hua Lee Hapuarachchige Chanditha Hapuarachchi Karen Caiyun Chen Khairunnisa' Mohamed Hussain Huixin Chen Swee Ling Low Lee Ching Ng Raymond Lin Mary Mah-Lee Ng Justin Jang Hann Chu Mosquito cellular factors and functions in mediating the infectious entry of chikungunya virus. |
topic_facet |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
description |
Chikungunya virus (CHIKV) is an arthropod-borne virus responsible for recent epidemics in the Asia Pacific regions. A customized gene expression microarray of 18,760 transcripts known to target Aedes mosquito genome was used to identify host genes that are differentially regulated during the infectious entry process of CHIKV infection on C6/36 mosquito cells. Several genes such as epsin I (EPN1), epidermal growth factor receptor pathway substrate 15 (EPS15) and Huntingtin interacting protein I (HIP1) were identified to be differentially expressed during CHIKV infection and known to be involved in clathrin-mediated endocytosis (CME). Transmission electron microscopy analyses further revealed the presence of CHIKV particles within invaginations of the plasma membrane, resembling clathrin-coated pits. Characterization of vesicles involved in the endocytic trafficking processes of CHIKV revealed the translocation of the virus particles to the early endosomes and subsequently to the late endosomes and lysosomes. Treatment with receptor-mediated endocytosis inhibitor, monodansylcadaverine and clathrin-associated drug inhibitors, chlorpromazine and dynasore inhibited CHIKV entry, whereas no inhibition was observed with caveolin-related drug inhibitors. Inhibition of CHIKV entry upon treatment with low-endosomal pH inhibitors indicated that low pH is essential for viral entry processes. CHIKV entry by clathrin-mediated endocytosis was validated via overexpression of a dominant-negative mutant of Eps15, in which infectious entry was reduced, while siRNA-based knockdown of genes associated with CME, low endosomal pH and RAB trafficking proteins exhibited significant levels of CHIKV inhibition. This study revealed, for the first time, that the infectious entry of CHIKV into mosquito cells is mediated by the clathrin-dependent endocytic pathway. |
format |
Article in Journal/Newspaper |
author |
Regina Ching Hua Lee Hapuarachchige Chanditha Hapuarachchi Karen Caiyun Chen Khairunnisa' Mohamed Hussain Huixin Chen Swee Ling Low Lee Ching Ng Raymond Lin Mary Mah-Lee Ng Justin Jang Hann Chu |
author_facet |
Regina Ching Hua Lee Hapuarachchige Chanditha Hapuarachchi Karen Caiyun Chen Khairunnisa' Mohamed Hussain Huixin Chen Swee Ling Low Lee Ching Ng Raymond Lin Mary Mah-Lee Ng Justin Jang Hann Chu |
author_sort |
Regina Ching Hua Lee |
title |
Mosquito cellular factors and functions in mediating the infectious entry of chikungunya virus. |
title_short |
Mosquito cellular factors and functions in mediating the infectious entry of chikungunya virus. |
title_full |
Mosquito cellular factors and functions in mediating the infectious entry of chikungunya virus. |
title_fullStr |
Mosquito cellular factors and functions in mediating the infectious entry of chikungunya virus. |
title_full_unstemmed |
Mosquito cellular factors and functions in mediating the infectious entry of chikungunya virus. |
title_sort |
mosquito cellular factors and functions in mediating the infectious entry of chikungunya virus. |
publisher |
Public Library of Science (PLoS) |
publishDate |
2013 |
url |
https://doi.org/10.1371/journal.pntd.0002050 https://doaj.org/article/dc5475e9afd047609fe4e783129565be |
geographic |
Arctic Pacific |
geographic_facet |
Arctic Pacific |
genre |
Arctic |
genre_facet |
Arctic |
op_source |
PLoS Neglected Tropical Diseases, Vol 7, Iss 2, p e2050 (2013) |
op_relation |
http://europepmc.org/articles/PMC3567007?pdf=render https://doaj.org/toc/1935-2735 1935-2735 doi:10.1371/journal.pntd.0002050 https://doaj.org/article/dc5475e9afd047609fe4e783129565be |
op_doi |
https://doi.org/10.1371/journal.pntd.0002050 |
container_title |
PLoS Neglected Tropical Diseases |
container_volume |
7 |
container_issue |
2 |
container_start_page |
e2050 |
_version_ |
1766343499724095488 |