Getah virus triggers ROS-mediated autophagy in mouse Leydig cells

IntroductionGetah virus (GETV) is a zoonotic virus transmitted via a mosquito-vertebrate cycle. While previous studies have explored the epidemiology and pathogenicity of GETV in various species, its molecular mechanisms remain largely unexplored.MethodsThis study investigated the impact of GETV inf...

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Main Authors: Fengqin Li, Lishuang Deng, Tong Xu, Lei Xu, Zhiwen Xu, Siyuan Lai, Yanru Ai, Yanqun Wang, Guangwen Yan, Ling Zhu
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-01-01
Series:Frontiers in Microbiology
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Online Access:https://www.frontiersin.org/articles/10.3389/fmicb.2024.1519694/full
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author Fengqin Li
Fengqin Li
Fengqin Li
Lishuang Deng
Tong Xu
Lei Xu
Zhiwen Xu
Zhiwen Xu
Siyuan Lai
Siyuan Lai
Yanru Ai
Yanru Ai
Yanqun Wang
Yanqun Wang
Guangwen Yan
Guangwen Yan
Ling Zhu
Ling Zhu
author_facet Fengqin Li
Fengqin Li
Fengqin Li
Lishuang Deng
Tong Xu
Lei Xu
Zhiwen Xu
Zhiwen Xu
Siyuan Lai
Siyuan Lai
Yanru Ai
Yanru Ai
Yanqun Wang
Yanqun Wang
Guangwen Yan
Guangwen Yan
Ling Zhu
Ling Zhu
author_sort Fengqin Li
collection DOAJ
description IntroductionGetah virus (GETV) is a zoonotic virus transmitted via a mosquito-vertebrate cycle. While previous studies have explored the epidemiology and pathogenicity of GETV in various species, its molecular mechanisms remain largely unexplored.MethodsThis study investigated the impact of GETV infection and associated molecular mechanisms on reactive oxygen species (ROS) and autophagy levels in mouse Leydig cells both in vivo and in vitro. The male mice and TM3 cells were treatment with N-acetylcysteine (NAC) to reduce cellular ROS levels. Rapamycin (Rapa) and 3-Methyladenine (3- MA) were used to change autophagy in both infected and uninfected TM3 cells.Results and DiscussionThe findings revealed that GETV infection in mouse testes speciffcally targeted Leydig cells and induced oxidative stress while enhancing autophagy in testicular tissue. Using TM3 cells as an in vitro model, the study confirmed GETV replication in this cell line, triggering increased ROS and autophagy levels. Treatment with N-acetylcysteine (NAC) to reduce cellular ROS levels markedly reduced autophagy in testicular tissue and TM3 cells infected with GETV. Interestingly, the use of rapamycin (Rapa) and 3-Methyladenine (3- MA) led to autophagy change in both infected and uninfected TM3 cells, with no signiffcant alterations in cellular ROS levels. These results indicate that GETV infection elevates ROS levels, subsequently inducing autophagy in mouse Leydig cells. We also found that autophagy plays an important role in GETV replication. When autophagy levels were reduced using NAC and 3-MA, a corresponding decrease in TCID50 was observed. Conversely, upregulation of autophagy using Rapa resulted in an increase in TCID50 of GETV. Therefore, we speculate that GETV may exploit the autophagy pathway to facilitate its replication. These ffndings illuminate the interplay between GETV and host cells, providing valuable insights for therapeutic strategies targeting autophagy in GETV infections.
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issn 1664-302X
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publisher Frontiers Media S.A.
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series Frontiers in Microbiology
spelling doaj-art-532d417489c04daa8ccc2b476bcaef122025-01-13T15:01:09ZengFrontiers Media S.A.Frontiers in Microbiology1664-302X2025-01-011510.3389/fmicb.2024.15196941519694Getah virus triggers ROS-mediated autophagy in mouse Leydig cellsFengqin Li0Fengqin Li1Fengqin Li2Lishuang Deng3Tong Xu4Lei Xu5Zhiwen Xu6Zhiwen Xu7Siyuan Lai8Siyuan Lai9Yanru Ai10Yanru Ai11Yanqun Wang12Yanqun Wang13Guangwen Yan14Guangwen Yan15Ling Zhu16Ling Zhu17College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, ChinaCollege of Animal Science, Xichang University, Xichang, ChinaKey Laboratory of Animal Disease Detection and Prevention in Panxi District, Xichang University, Xichang, ChinaCollege of Veterinary Medicine, Sichuan Agricultural University, Chengdu, ChinaCollege of Veterinary Medicine, Sichuan Agricultural University, Chengdu, ChinaCollege of Veterinary Medicine, Sichuan Agricultural University, Chengdu, ChinaCollege of Veterinary Medicine, Sichuan Agricultural University, Chengdu, ChinaKey Laboratory of Animal Diseases and Human Health of Sichuan Province, Sichuan Agricultural University, Chengdu, ChinaCollege of Veterinary Medicine, Sichuan Agricultural University, Chengdu, ChinaKey Laboratory of Animal Diseases and Human Health of Sichuan Province, Sichuan Agricultural University, Chengdu, ChinaCollege of Veterinary Medicine, Sichuan Agricultural University, Chengdu, ChinaKey Laboratory of Animal Diseases and Human Health of Sichuan Province, Sichuan Agricultural University, Chengdu, ChinaCollege of Animal Science, Xichang University, Xichang, ChinaKey Laboratory of Animal Disease Detection and Prevention in Panxi District, Xichang University, Xichang, ChinaCollege of Animal Science, Xichang University, Xichang, ChinaKey Laboratory of Animal Disease Detection and Prevention in Panxi District, Xichang University, Xichang, ChinaCollege of Veterinary Medicine, Sichuan Agricultural University, Chengdu, ChinaKey Laboratory of Animal Diseases and Human Health of Sichuan Province, Sichuan Agricultural University, Chengdu, ChinaIntroductionGetah virus (GETV) is a zoonotic virus transmitted via a mosquito-vertebrate cycle. While previous studies have explored the epidemiology and pathogenicity of GETV in various species, its molecular mechanisms remain largely unexplored.MethodsThis study investigated the impact of GETV infection and associated molecular mechanisms on reactive oxygen species (ROS) and autophagy levels in mouse Leydig cells both in vivo and in vitro. The male mice and TM3 cells were treatment with N-acetylcysteine (NAC) to reduce cellular ROS levels. Rapamycin (Rapa) and 3-Methyladenine (3- MA) were used to change autophagy in both infected and uninfected TM3 cells.Results and DiscussionThe findings revealed that GETV infection in mouse testes speciffcally targeted Leydig cells and induced oxidative stress while enhancing autophagy in testicular tissue. Using TM3 cells as an in vitro model, the study confirmed GETV replication in this cell line, triggering increased ROS and autophagy levels. Treatment with N-acetylcysteine (NAC) to reduce cellular ROS levels markedly reduced autophagy in testicular tissue and TM3 cells infected with GETV. Interestingly, the use of rapamycin (Rapa) and 3-Methyladenine (3- MA) led to autophagy change in both infected and uninfected TM3 cells, with no signiffcant alterations in cellular ROS levels. These results indicate that GETV infection elevates ROS levels, subsequently inducing autophagy in mouse Leydig cells. We also found that autophagy plays an important role in GETV replication. When autophagy levels were reduced using NAC and 3-MA, a corresponding decrease in TCID50 was observed. Conversely, upregulation of autophagy using Rapa resulted in an increase in TCID50 of GETV. Therefore, we speculate that GETV may exploit the autophagy pathway to facilitate its replication. These ffndings illuminate the interplay between GETV and host cells, providing valuable insights for therapeutic strategies targeting autophagy in GETV infections.https://www.frontiersin.org/articles/10.3389/fmicb.2024.1519694/fullGetah virusROSautophagymouseLeydig cells
spellingShingle Fengqin Li
Fengqin Li
Fengqin Li
Lishuang Deng
Tong Xu
Lei Xu
Zhiwen Xu
Zhiwen Xu
Siyuan Lai
Siyuan Lai
Yanru Ai
Yanru Ai
Yanqun Wang
Yanqun Wang
Guangwen Yan
Guangwen Yan
Ling Zhu
Ling Zhu
Getah virus triggers ROS-mediated autophagy in mouse Leydig cells
Frontiers in Microbiology
Getah virus
ROS
autophagy
mouse
Leydig cells
title Getah virus triggers ROS-mediated autophagy in mouse Leydig cells
title_full Getah virus triggers ROS-mediated autophagy in mouse Leydig cells
title_fullStr Getah virus triggers ROS-mediated autophagy in mouse Leydig cells
title_full_unstemmed Getah virus triggers ROS-mediated autophagy in mouse Leydig cells
title_short Getah virus triggers ROS-mediated autophagy in mouse Leydig cells
title_sort getah virus triggers ros mediated autophagy in mouse leydig cells
topic Getah virus
ROS
autophagy
mouse
Leydig cells
url https://www.frontiersin.org/articles/10.3389/fmicb.2024.1519694/full
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