دورية أكاديمية
Human Parainfluenza Virus Type 1 C Proteins Are Nonessential Proteins That Inhibit the Host Interferon and Apoptotic Responses and Are Required for Efficient Replication in Nonhuman Primates
| العنوان: | Human Parainfluenza Virus Type 1 C Proteins Are Nonessential Proteins That Inhibit the Host Interferon and Apoptotic Responses and Are Required for Efficient Replication in Nonhuman Primates |
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| المؤلفون: | Bartlett, E. J., Cruz, A.-M., Esker, J., Castano, A., Schomacker, H., Surman, S. R., Hennessey, M., Boonyaratanakornkit, J., Pickles, R. J., Collins, P. L., Murphy, B. R., Schmidt, A. C. |
| المصدر: | Journal of Virology, 82(18) |
| سنة النشر: | 2008 |
| المجموعة: | Carolina Digital Repository (UNC - University of North Carolina) |
| مصطلحات موضوعية: | Interferon, Replicación, Paramyxovirus, Réplication, Paramyxoviridae, Interféron, Apoptose, Virology, Parainfluenza virus humain 1, Cytokine, Paramyxovirinae, Mammalia, Proteína C, Mononegavirales, Virologie, Protein C, Replication, Interferón, Virus, Virología, Vertebrata, Citoquina, Human parainfluenza virus 1, Primates, Protéine C, Animal, Apoptosis |
| الوصف: | Recombinant human parainfluenza virus type 1 (rHPIV1) was modified to create rHPIV1-P(C−), a virus in which expression of the C proteins (C′, C, Y1, and Y2) was silenced without affecting the amino acid sequence of the P protein. Infectious rHPIV1-P(C−) was readily recovered from cDNA, indicating that the four C proteins were not essential for virus replication. Early during infection in vitro, rHPIV1-P(C−) replicated as efficiently as wild-type (wt) HPIV1, but its titer subsequently decreased coincident with the onset of an extensive cytopathic effect not observed with wt rHPIV1. rHPIV1-P(C−) infection, but not wt rHPIV1 infection, induced caspase 3 activation and nuclear fragmentation in LLC-MK2 cells, identifying the HPIV1 C proteins as inhibitors of apoptosis. In contrast to wt rHPIV1, rHPIV1-P(C−) and rHPIV1-CF170S, a mutant encoding an F170S substitution in C, induced interferon (IFN) and did not inhibit IFN signaling in vitro. However, only rHPIV1-P(C−) induced apoptosis. Thus, the anti-IFN and antiapoptosis activities of HPIV1 were separable: both activities are disabled in rHPIV1-P(C−), whereas only the anti-IFN activity is disabled in rHPIV1-CF170S. In African green monkeys (AGMs), rHPIV1-P(C−) was considerably more attenuated than rHPIV1-CF170S, suggesting that disabling the anti-IFN and antiapoptotic activities of HPIV1 had additive effects on attenuation in vivo. Although rHPIV1-P(C−) protected against challenge with wt HPIV1, its highly restricted replication in AGMs and in primary human airway epithelial cell cultures suggests that it might be overattenuated for use as a vaccine. Thus, the C proteins of HPIV1 are nonessential but have anti-IFN and antiapoptosis activities required for virulence in primates. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| العلاقة: | https://doi.org/10.17615/vfv2-7258Test; https://cdr.lib.unc.edu/downloads/db78tk580?file=thumbnailTest; https://cdr.lib.unc.edu/downloads/db78tk580Test |
| DOI: | 10.17615/vfv2-7258 |
| الإتاحة: | https://doi.org/10.17615/vfv2-7258Test https://cdr.lib.unc.edu/downloads/db78tk580?file=thumbnailTest https://cdr.lib.unc.edu/downloads/db78tk580Test |
| حقوق: | http://rightsstatements.org/vocab/InC/1.0Test/ |
| رقم الانضمام: | edsbas.22CF256C |
| قاعدة البيانات: | BASE |
| DOI: | 10.17615/vfv2-7258 |
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