HEV ORF3 downregulatesCD14 and CD64 to impair macrophages phagocytosis through inhibiting JAK/STAT pathway.
Hepatitis E virus (HEV) could induce chronic hepatitis and liver failure with high mortality through unknown mechanisms. The previous study showed that the HEV open reading frames 3 (ORF3) could inhibit macrophages inflammatory response. Impaired macrophages phagocytosis was also found in patients infected with HEV and its nucleic acids could be detected in macrophages. To elucidate the role of HEV ORF3 on phagocytosis, the phagocytosis activation was measured by phagocytosis test, flow cytometry, and phalloidin staining. Meanwhile, the expression of key phagocytic receptors and the activation of transduction pathway were investigated by using reverse transcription real-time quantitative polymerase chain reaction (RT-qPCR) and Western blot analysis. Results of phagocytosis test showed that the HEV ORF3 could significantly impair the absorption capacity of latex beads. Furthermore, results of RT-qPCR and Western blot analysis showed that the expression of CD14 and CD64 decreased. Afterward, the present study showed that the activation of Janus kinase-signal transducer and activator of transcription (JAK/STAT) signaling pathway was inhibited by HEV ORF3 and downregulation of CD14 and CD64 could be reversed by interferon γ, one activator of the JAK1/STAT1 signaling pathway. In conclusion, HEV ORF3 could significantly impair the phagocytosis of macrophage by downregulating expression of CD14 and CD64, which may function by inhibiting the activation of the JAK1/STAT1 signaling pathway.
['Lei|Qingsong|Q|', 'Li|Lin|L|0000-0001-9024-4014', 'Huang|Wenxiang|W|0000-0002-8572-9313', 'Qin|Bo|B|0000-0001-7926-7549', 'Zhang|Shujun|S|0000-0002-9103-7671']
D015536:Down-Regulation D016752:Hepatitis E virus D006801:Humans D053612:Janus Kinases D018950:Lipopolysaccharide Receptors D008264:Macrophages D016366:Open Reading Frames D010587:Phagocytosis D017452:Receptors, IgG D050794:STAT1 Transcription Factor D015398:Signal Transduction D000074084:THP-1 Cells
CD64 phagocytosis hepatitis E virus CD14 Janus kinase-signal transducer and activator of transcription