Low Oxygen Tension Enhances Hepatitis C Virus Replication

被引:47
作者
Vassilaki, N. [1 ]
Kalliampakou, K. I. [1 ]
Kotta-Loizou, I. [1 ]
Befani, C. [2 ]
Liakos, P. [2 ]
Simos, G. [2 ]
Mentis, A. F. [3 ]
Kalliaropoulos, A. [3 ]
Doumba, P. P. [4 ]
Smirlis, D. [1 ]
Foka, P. [1 ]
Bauhofer, O. [5 ]
Poenisch, M. [5 ]
Windisch, M. P. [6 ]
Lee, M. E. [6 ]
Koskinas, J. [6 ]
Bartenschlager, R. [5 ]
Mavromara, P. [1 ]
机构
[1] HPI, Athens, Greece
[2] Univ Thessaly, Biochem Lab, Sch Med, Larisa, Greece
[3] HPI, Lab Med Microbiol, Athens, Greece
[4] Hippokrateion Hosp, Dept Internal Med 2, Med Sch Athens, Athens, Greece
[5] Heidelberg Univ, Dept Infect Dis, Heidelberg, Germany
[6] Inst Pasteur Korea, Songnam, South Korea
关键词
OPEN READING FRAME; INDUCIBLE FACTOR-I; CREATINE-KINASE; PYRUVATE-KINASE; RNA TRANSLATION; GENE-EXPRESSION; HEPATOMA-CELLS; HYPOXIA; CANCER; INDUCTION;
D O I
10.1128/JVI.02534-12
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
Low oxygen tension exerts a significant effect on the replication of several DNA and RNA viruses in cultured cells. In vitro propagation of hepatitis C virus (HCV) has thus far been studied under atmospheric oxygen levels despite the fact that the liver tissue microenvironment is hypoxic. In this study, we investigated the efficiency of HCV production in actively dividing or differentiating human hepatoma cells cultured under low or atmospheric oxygen tensions. By using both HCV replicons and infection-based assays, low oxygen was found to enhance HCV RNA replication whereas virus entry and RNA translation were not affected. Hypoxia signaling pathway-focused DNA microarray and real-time quantitative reverse transcription-PCR (qRT-PCR) analyses revealed an upregulation of genes related to hypoxic stress, glycolytic metabolism, cell growth, and proliferation when cells were kept under low (3% [vol/vol]) oxygen tension, likely reflecting cell adaptation to anaerobic conditions. Interestingly, hypoxia-mediated enhancement of HCV replication correlated directly with the increase in anaerobic glycolysis and creatine kinase B (CKB) activity that leads to elevated ATP production. Surprisingly, activation of hypoxia-inducible factor alpha (HIF-alpha) was not involved in the elevation of HCV replication. Instead, a number of oncogenes known to be associated with glycolysis were upregulated and evidence that these oncogenes contribute to hypoxia-mediated enhancement of HCV replication was obtained. Finally, in liver biopsy specimens of HCV-infected patients, the levels of hypoxia and anaerobic metabolism markers correlated with HCV RNA levels. These results provide new insights into the impact of oxygen tension on the intricate HCV-host cell interaction.
引用
收藏
页码:2935 / 2948
页数:14
相关论文
共 50 条
  • [31] Modulation of hepatitis C virus replication by iron and hepcidin in Huh7 hepatocytes
    Bartolomei, Giody
    Cevik, Recep Emrah
    Marcello, Alessandro
    JOURNAL OF GENERAL VIROLOGY, 2011, 92 : 2072 - 2081
  • [32] Interference with ERK and STAT signaling pathways and inhibition of hepatitis C virus replication by ribavirin
    Zhao, Lan-Juan
    Wang, Wen
    Liu, Yuan
    Ren, Hao
    Qi, Zhong-Tian
    ANTIVIRAL RESEARCH, 2012, 96 (02) : 260 - 268
  • [33] Downregulation of hepatitis C virus replication by miR-196a using lentiviral vectors
    Shafaati, Maryam
    Jamalidoust, Marzieh
    Kargar, Mohammad
    Arefian, Ehsan
    Kafilzadeh, Farshid
    MICROBIOLOGY AND IMMUNOLOGY, 2021, 65 (04) : 161 - 170
  • [34] Molecular biology and replication of hepatitis E virus
    Cao, Dianjun
    Meng, Xiang-Jin
    EMERGING MICROBES & INFECTIONS, 2012, 1
  • [35] Circadian control of hepatitis B virus replication
    Zhuang, Xiaodong
    Forde, Donall
    Tsukuda, Senko
    D'Arienzo, Valentina
    Mailly, Laurent
    Harris, James M.
    Wing, Peter A. C.
    Borrmann, Helene
    Schilling, Mirjam
    Magri, Andrea
    Rubio, Claudia Orbegozo
    Maidstone, Robert J.
    Iqbal, Mudassar
    Garzon, Miguel
    Minisini, Rosalba
    Pirisi, Mario
    Butterworth, Sam
    Balfe, Peter
    Ray, David W.
    Watashi, Koichi
    Baumert, Thomas F.
    McKeating, Jane A.
    NATURE COMMUNICATIONS, 2021, 12 (01)
  • [36] The regulation of HBx in hepatitis B virus replication
    Guo, Yandan
    Wang, Jingwen
    Yuan, Sen
    Guo, Shuting
    Liu, Dan
    Sun, Guihong
    CHINESE SCIENCE BULLETIN-CHINESE, 2019, 64 (30): : 3101 - 3108
  • [37] LncRNA PCNAP1 modulates hepatitis B virus replication and enhances tumor growth of liver cancer
    Feng, Jinyan
    Yang, Guang
    Liu, Yunxia
    Gao, Yuen
    Zhao, Man
    Bu, Yanan
    Yuan, Hongfeng
    Yuan, Ying
    Yun, Haolin
    Sun, Mingming
    Gao, Hongwei
    Zhang, Shuqin
    Liu, Zixian
    Yin, Ming
    Song, Xijun
    Miao, Zhenchuan
    Lin, Zhongqing
    Zhang, Xiaodong
    THERANOSTICS, 2019, 9 (18): : 5227 - 5245
  • [38] Hypoxia Enhances the Replication of Oncolytic Herpes Simplex Virus
    Aghi, Manish K.
    Liu, Ta-Chiang
    Rabkin, Samuel
    Martuza, Robert L.
    MOLECULAR THERAPY, 2009, 17 (01) : 51 - 56
  • [39] Low Oxygen Tension Enhances Proliferation and Maintains Stemness of Adipose Tissue-Derived Stromal Cells
    Yamamoto, Yoritsuna
    Fujita, Masanori
    Tanaka, Yuji
    Kojima, Itaru
    Kanatani, Yasuhiro
    Ishihara, Masayuki
    Tachibana, Shoichi
    BIORESEARCH OPEN ACCESS, 2013, 2 (03): : 199 - 205
  • [40] Low oxygen tension increases mitochondrial membrane potential and enhances expression of antioxidant genes and implantation protein of mouse blastocyst cultured in vitro
    Ma, Yun-Yi
    Chen, Huei-Wen
    Tzeng, Chii-Ruey
    JOURNAL OF OVARIAN RESEARCH, 2017, 10