Abstract
Flaviviruses are positive-stranded RNA viruses that are a public health problem because of their widespread distribution and their ability to cause a variety of diseases in humans. West Nile virus is a mosquito-borne member of this genus and is the etiologic agent of West Nile encephalitis. Clinical manifestations of West Nile virus infection are diverse, and their pathogenic mechanisms depend on complex virus-cell interactions. In the present work, we used proteomics technology to analyze early Vero cell response to West Nile infection. The differential proteomes were resolved 24 h postinfection using two-dimensional DIGE followed by mass spectrometry identification. Quantitative analysis (at least 2-fold quantitative alteration, p < 0.05) revealed 127 differentially expressed proteins with 68 up-regulated proteins and 59 down-regulated proteins of which 93 were successfully identified. The implication for mammalian cellular responses to this neurotropic flavivirus infection was analyzed and made possible more comprehensive characterization of the virus-host interactions involved in pathogenesis. The present study thus provides large scale protein-related information that should be useful for understanding how the host metabolism is modified by West Nile infection and for identifying new potential targets for antiviral therapy.
Highlights
Flaviviruses are positive-stranded RNA viruses that are a public health problem because of their widespread distribution and their ability to cause a variety of diseases in humans
West Nile virus (WNV)1 is a mosquito-borne flavivirus belonging to the Japanese encephalitis virus (JEV) serocomplex
DNA fragmentation by TUNEL assay was controlled with mock- and WNV-infected Vero cells cultivated for 36 h with a m.o.i. of 1
Summary
Flaviviruses are positive-stranded RNA viruses that are a public health problem because of their widespread distribution and their ability to cause a variety of diseases in humans. Clinical manifestations of West Nile virus infection are diverse, and their pathogenic mechanisms depend on complex virus-cell interactions. We used proteomics technology to analyze early Vero cell response to West Nile infection. The implication for mammalian cellular responses to this neurotropic flavivirus infection was analyzed and made possible more comprehensive characterization of the virus-host interactions involved in pathogenesis. The present study provides large scale protein-related information that should be useful for understanding how the host metabolism is modified by West Nile infection and for identifying new potential targets for antiviral therapy. West Nile virus (WNV) is a mosquito-borne flavivirus belonging to the Japanese encephalitis virus (JEV) serocomplex. Since 1999, WNV from lineage 1 (NY99) has reached North America where, in 2002, it caused the largest arboviral meningoencephalitis outbreak ever recorded in this area [4]. It has been demonstrated that flaviviruses can induce cell death directly through viral replication and the production of proapoptotic proteins (6 –11), but the mechanism of pathogenesis has not been elucidated
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