Role of Itk signalling in the interaction between influenza A virus and T-cells.
Although the T-cell-mediated immune response to influenza virus has been studied extensively, little information is available on the direct interaction between influenza virus and T-cells that pertains to severe diseases in humans and animals. To address these issues, we utilized the BALB/c mouse model combined with primary T-cells infected with A/WSN/33 influenza virus to investigate whether influenza virus has an affinity for T-cells in vivo. We observed that small proportions of CD4(+) T-cells and CD8(+) T-cells in spleen and thymus expressed viral proteins in infected mice. A significant proportion of mouse primary T-cells displayed expression of α-2,6 sialic acid-linked influenza virus receptor and were infected directly by influenza A virus. These experiments reveal that there exists a population of T-cells that is susceptible to influenza A virus infection. Furthermore, we employed human Jurkat T-cells to investigate the virus-T-cell interaction, with particular emphasis on understanding whether Itk (interleukin-2-inducible T-cell kinase), a Tec family tyrosine kinase that regulates T-cell activation, is involved in virus infection of T-cells. Interestingly, influenza virus infection resulted in an increased recruitment of Itk to the plasma membrane and an increased level of phospholipase C-γ1 (PLC-γ1) phosphorylation, suggesting that Itk/PLC-γ1 signalling is activated by the virus infection. We demonstrated that depletion of Itk inhibited the replication of influenza A virus, whereas overexpression of Itk increased virus replication. These results indicate that Itk is required for efficient replication of influenza virus in infected T-cells.
College of Life Sciences, Fujian Agriculture and Forestry University, Fuzhou, PR China.|CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences (CAS), Beijing, PR China.
Kewei
K
Fan
College of Animal Science and Technology, Southwest University, Chongqing, PR China.|CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences (CAS), Beijing, PR China.
Yinping
Y
Jia
CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences (CAS), Beijing, PR China.
Song
S
Wang
CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences (CAS), Beijing, PR China.
Hua
H
Li
College of Life Sciences, Fujian Agriculture and Forestry University, Fuzhou, PR China.
Defeng
D
Wu
Gene Therapy Program, Department of Medicine and Genetics, Louisiana State University Health Sciences Center, New Orleans, LA, USA.
Guoshun
G
Wang
CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences (CAS), Beijing, PR China.
Ji-Long
JL
Chen
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000821:virology*; D018414:CD8-Positive T-Lymphocytes / Q000821:virology*; D002462:Cell Membrane / Q000737:chemistry; D002478:Cells, Cultured; D054884:Host-Pathogen Interactions; D006801:Humans; D009980:Influenza A virus / Q000472:pathogenicity*; D051379:Mice; D008807:Mice, Inbred BALB C; D051966:Phospholipase C gamma / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D015398:Signal Transduction; D013154:Spleen / Q000276:immunology / Q000821:virology; D013950:Thymus Gland / Q000276:immunology / Q000821:virology; D014779:Virus Replication
D011505:Protein-Tyrosine Kinases; C080813:emt protein-tyrosine kinase; D051966:Phospholipase C gamma