Sialidase Activity of Influenza A Virus in an Endocytic Pathway Enhances Viral Replication
| العنوان: | Sialidase Activity of Influenza A Virus in an Endocytic Pathway Enhances Viral Replication |
|---|---|
| المؤلفون: | Yasuo Suzuki, Chao-Tan Guo, Hideo Goto, Tadanobu Takahashi, Takashi Suzuki, Daisei Miyamoto, Yoshihiro Kawaoka, Kazuya I.P.J. Hidari |
| المصدر: | Journal of Virology. 79:11705-11715 |
| بيانات النشر: | American Society for Microbiology, 2005. |
| سنة النشر: | 2005 |
| مصطلحات موضوعية: | Male, viruses, Immunology, Orthomyxoviridae, Neuraminidase, Hemagglutinin (influenza), Biology, Transfection, Virus Replication, medicine.disease_cause, Sialidase, Guanidines, Microbiology, Cell Line, Mice, chemistry.chemical_compound, Dogs, Virology, Enzyme Stability, Influenza, Human, Influenza A virus, medicine, Animals, Humans, Zanamivir, Enzyme Inhibitors, Late endosome, Pyrans, biochemical phenomena, metabolism, and nutrition, Hydrogen-Ion Concentration, biology.organism_classification, Endocytosis, Virus-Cell Interactions, Sialic acid, Mice, Inbred C57BL, Viral replication, chemistry, Insect Science, Sialic Acids, biology.protein |
| الوصف: | N2 neuraminidase (NA) genes of the 1957 and 1968 pandemic influenza virus strains possessed avian-like low-pH stability of sialidase activity, unlike most epidemic strains. We generated four reverse-genetics viruses from a genetic background of A/WSN/33 (H1N1) that included parental N2 NAs of 1968 pandemic (H3N2) and epidemic (H2N2) strains or their counterpart N2 NAs in which the low-pH stability of the sialidase activity was changed by substitutions of one or two amino acid residues. We found that the transfectant viruses bearing low-pH-stable sialidase (WSN/Stable-NAs) showed 25- to 80-times-greater ability to replicate in Madin-Darby canine kidney (MDCK) cells than did the transfectant viruses bearing low-pH-unstable sialidase (WSN/Unstable-NAs). Enzymatic activities of WSN/Stable-NAs were detected in endosomes of MDCK cells after 90 min of virus internalization by in situ fluorescent detection with 5-bromo-4-chloro-indole-3-yl-α- N -acetylneuraminic acid and Fast Red Violet LB. Inhibition of sialidase activity of WSN/Stable-NAs on the endocytic pathway by pretreatment with 4-guanidino-2,4-dideoxy- N -acetylneuraminic acid (zanamivir) resulted in a significant decrease in progeny viruses. In contrast, the enzymatic activities of WSN/Unstable-NAs, the replication of which had no effect on pretreatment with zanamivir, were undetectable in cells under the same conditions. Hemadsorption assays of transfectant-virus-infected cells revealed that the low-pH stability of the sialidase had no effect on the process of removal of sialic acid from hemagglutinin in the Golgi regions. Moreover, high titers of viruses were recovered from the lungs of mice infected with WSN/Stable-NAs on day 3 after intranasal inoculation, but WSN/Unstable-NAs were cleared from the lungs of the mice. These results indicate that sialidase activity in late endosome/lysosome traffic enhances influenza A virus replication. |
| تدمد: | 1098-5514 0022-538X |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::0cfbfd13e5cc1519f5c841d834a27d92Test https://doi.org/10.1128/jvi.79.18.11705-11715.2005Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....0cfbfd13e5cc1519f5c841d834a27d92 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 10985514 0022538X |
|---|