ABSTRACT
The G1 cytoplasmic tail of Hantaan virus (HTNV) harbors a highly conserved region, which is homologous to immunoreceptor tyrosine-based activation motifs (ITAM) and is termed the ITAM-like sequence. To demonstrate the potential signal-transducing activity of G1 ITAM-like sequence resembling the canonical ITAM within immune and endothelial cells, a series of experiments were performed to define its interaction with cellular kinases. The synthesized G1 ITAM-like peptide was shown to coprecipitate with cellular phosphoprotein complexes by an immune-complex kinase assay. Mutational analyses showed that this ITAM-like sequence was a substrate for the Src family kinase Fyn, and two conserved tyrosine residues were required for coprecipitating Lyn, Syk, and ZAP-70 kinases. These findings demonstrated that HTNV envelope glycoprotein G1 contains a functional ITAM-like sequence in its cytoplasmic tail, which can bind critical cellular kinases that regulate immune and endothelial cell functions.
Subject(s)
Humans , Amino Acid Sequence , Cells, Cultured , Hantaan virus , Chemistry , Physiology , Intracellular Signaling Peptides and Proteins , Physiology , Molecular Sequence Data , Phosphorylation , Protein-Tyrosine Kinases , Physiology , Proto-Oncogene Proteins c-fyn , Physiology , Signal Transduction , Syk Kinase , Viral Envelope Proteins , Chemistry , PhysiologyABSTRACT
<p><b>OBJECTIVE</b>To investigate the role of neuronal apoptosis in organophosphorus poisoning-induced delayed neuropathy (OPIDN) and its dynamic pathological changes.</p><p><b>METHODS</b>To establish OPIDN animal model, triorthocresyl phosphate (TOCP)was given to hens with a single dose (1 000 mg/kg, im). Changes of neuropathology, number of neurons and apoptotic cells in the third lumbar spinal cord were observed by HE, Nissl and TUNEL methods 3, 5, 7, 10, 14, 18 days after injection.</p><p><b>RESULTS</b>The hens showed OPIDN typical signs (progressive ataxia and hypotonia) about 9 days after TOCP exposure. HE staining revealed dark red nucleus in neurons of anterior horn of lumbar spinal cord 5 days after exposure, but this phenomenon disappeared 18 days later. Nissl method showed that the number of neurons in anterior horn of spinal cord decreased [from (82 +/- 4) cell/mm(2) to (66 +/- 6) cell/mm(2)]. TUNEL positive cells began to appear [(22 +/- 2) cell/mm(2)] 5 days after TOCP exposure, and reached the peak [(27 +/- 3) cell/mm(2)] 7 days later, and disappeared 18 days later.</p><p><b>CONCLUSION</b>Neuronal apoptosis in anterior horn of spinal cord of hens appeared in OPIDN, suggesting that cellular apoptosis may play an important role in the pathogenesis of OPIDN.</p>