Function of Small Hydrophobic Proteins of Paramyxovirus
| Autor: | Alicia Klatt, Andrew J. Henderson, Rebecca L. Wilson, Ping Wang, Erica C. Taddeo, Biao He, Sandra Fuentes |
|---|---|
| Rok vydání: | 2006 |
| Předmět: |
Paramyxoviridae
viruses Retroviridae Proteins Oncogenic Immunology Apoptosis Viral Plaque Assay Models Biological Microbiology Cell Line law.invention Mice Viral Proteins Tissue culture Cytopathogenic Effect Viral law Virology Chlorocebus aethiops Animals Humans Rubulavirus Gene Recombination Genetic Reporter gene biology Tumor Necrosis Factor-alpha biology.organism_classification Molecular biology Virus-Cell Interactions Open reading frame Mumps virus Membrane protein Insect Science Parainfluenza Virus 5 Recombinant DNA Cattle |
| Zdroj: | Journal of Virology. 80:1700-1709 |
| ISSN: | 1098-5514 0022-538X |
| DOI: | 10.1128/jvi.80.4.1700-1709.2006 |
| Popis: | Mumps virus (MuV), a rubulavirus of the paramyxovirus family, causes acute infections in humans. MuV has seven genes including a small hydrophobic (SH) gene, which encodes a type I membrane protein of 57 amino acid residues. The function of the SH protein is not clear, although its expression is not necessary for growth of MuV in tissue culture cells. It is speculated that MuV SH plays a role in viral pathogenesis. Simian virus 5 (SV5), a closely related rubulavirus, encodes a 44-amino-acid-residue SH protein. Recombinant SV5 lacking the SH gene (rSV5ΔSH) is viable and has no growth defect in tissue culture cells. However, rSV5ΔSH induces apoptosis in tissue culture cells and is attenuated in vivo. Neutralizing antibodies against tumor necrosis factor alpha (TNF-α) and TNF-α receptor 1 block rSV5ΔSH-induced apoptosis, suggesting that SV5 SH plays an essential role in blocking the TNF-α-mediated apoptosis pathway. Because MuV is closely related to SV5, we hypothesize that the SH protein of MuV has a function similar to that of SV5, even though there is no sequence homology between them. To test this hypothesis and to study the function of MuV SH, we have replaced the open reading frame (ORF) of SV5 SH with the ORF of MuV SH in a SV5 genome background. The recombinant SV5 (rSV5ΔSH+MuV-SH) was analyzed in comparison with SV5. It was found that rSV5ΔSH+MuV-SH was viable and behaved like wild-type SV5, suggesting that MuV SH has a function similar to that of SV5 SH. Furthermore, both ectopically expressed SV5 SH and MuV SH blocked activation of NF-κB by TNF-α in a reporter gene assay, suggesting that both SH proteins can inhibit TNF-α signaling. |
| Databáze: | OpenAIRE |
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