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. 2019 Oct 18;11(10):962.
doi: 10.3390/v11100962.

In Vitro and In Vivo Metabolomic Profiling after Infection with Virulent Newcastle Disease Virus

Panrao Liu  1 , Yuncong Yin  2 , Yabin Gong  3 , Xusheng Qiu  4 , Yingjie Sun  5 , Lei Tan  6 , Cuiping Song  7 , Weiwei Liu  8 , Ying Liao  9 , Chunchun Meng  10 , Chan Ding  11   12
Affiliations

In Vitro and In Vivo Metabolomic Profiling after Infection with Virulent Newcastle Disease Virus

Panrao Liu et al. Viruses. .

Abstract

Newcastle disease (ND) is an acute, febrile, highly contagious disease caused by the virulent Newcastle disease virus (vNDV). The disease causes serious economic losses to the poultry industry. However, the metabolic changes caused by vNDV infection remain unclear. The objective of this study was to determine the metabolomic profiling after infection with vNDV. DF-1 cells infected with the vNDV strain Herts/33 and the lungs from Herts/33-infected specific pathogen-free (SPF) chickens were analyzed via ultra-high-performance liquid chromatography/quadrupole time-of-flight tandem mass spectrometry (UHPLC-QTOF-MS) in combination with multivariate statistical analysis. A total of 305 metabolites were found to have changed significantly after Herts/33 infection, and most of them belong to the amino acid and nucleotide metabolic pathway. It is suggested that the increased pools of amino acids and nucleotides may benefit viral protein synthesis and genome amplification to promote NDV infection. Similar results were also confirmed in vivo. Identification of these metabolites will provide information to further understand the mechanism of vNDV replication and pathogenesis.

Keywords: UHPLC-QTOF-MS; in vitro and in vivo; metabolomic analysis; virulent Newcastle disease virus.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Detection of NDV infection in Herts/33-infected DF-1 cells. The cells were infected with NDV Herts/33 at 1 MOI, and samples were collected for detection at 6, 12, 18, and 24 h. (A) The NDV titers were determined using TCID50. (B) The NP protein of NDV was assessed by Western blot.
Figure 2
Figure 2
OPLS-DA model for the mock-infected and Herts/33-infected cells in different time courses. The OPLS-DA model (A,B) was derived from the UHPLC-QTOF-MS metabolomic profiles of the DF-1 cell samples. (A) was derived from POS and (B) from NEG.
Figure 3
Figure 3
Volcano plots for the mock-infected and Herts/33-infected cells in different time courses. (A) was derived from POS and (B) from NEG. Each point in the volcanic map represents a metabolite. Red: Upregulation; blue: Downregulation; gray: Not significant.
Figure 4
Figure 4
Analysis of differentially expressed metabolites in DF-1 cells infected with Herts/33 in different time courses. (A) Numbers of metabolites upregulated (red) and downregulated (blue) in infected cells. Venn diagrams (B,C) provide an overview of the global metabolite features in terms of their similarity and uniqueness for the five sampled groups. (B) was derived from POS and (C) from NEG. (D) Heatmap of hierarchical clustering analysis. Each column represents one sample, and each row represents one differential metabolite. The color of each cell represents the relative level of the differential metabolites. Red: Upregulation; green: Downregulation.
Figure 5
Figure 5
Bubble plots of the metabolic pathway analysis for DF-1 cells infected with Herts/33 in different time courses. (A–D) were derived from POS and (E–H) from NEG. Each bubble represents a metabolic pathway. The x-axis represents a pathway impact value in the topology analysis, and larger bubbles represent higher pathway impact values. The y-axis represents the p-value of the metabolic pathway in the enrichment analysis, and the darker color of the bubble represents higher pathway enrichment.
Figure 6
Figure 6
Schematic representation of altered metabolic pathways in DF-1 cells infected with Herts/33. Metabolomics of Herts/33-infected cells was performed by UHPLC-QTOF-MS, and many metabolites and associated metabolic pathways were significantly altered with the development of Herts/33, including amino acid metabolism, nucleotide metabolism, and urea cycles. Red: Upregulation; green: Downregulation.
Figure 7
Figure 7
Analysis of differentially expressed metabolites in chickens infected with NDV Herts/33. (A) Hematoxylin and eosin staining of cells in a chicken lung (20 times magnification). Black arrows indicate lesions. (B) Numbers of metabolites upregulated (red) and downregulated (blue) in infected cells. (C) Heatmap of hierarchical clustering analysis. Each column represents one sample, and each row represents one differential metabolite. The color of each cell represents the relative level of the differential metabolite. Red: Upregulation; green: Downregulation.
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