Abstract:
UNLABELLED:Avian metapneumovirus (aMPV), also known as avian pneumovirus or turkey rhinotracheitis virus, is the causative agent of turkey rhinotracheitis and is associated with swollen head syndrome in chickens. Since its discovery in the 1970s, aMPV has been recognized as an economically important pathogen in the poultry industry worldwide. The conserved region VI (CR VI) of the large (L) polymerase proteins of paramyxoviruses catalyzes methyltransferase (MTase) activities that typically methylate viral mRNAs at guanine N-7 (G-N-7) and ribose 2'-O positions. In this study, we generated a panel of recombinant aMPV (raMPV) Colorado strains carrying mutations in the S-adenosyl methionine (SAM) binding site in the CR VI of L protein. These recombinant viruses were specifically defective in ribose 2'-O, but not G-N-7 methylation and were genetically stable and highly attenuated in cell culture and viral replication in the upper and lower respiratory tracts of specific-pathogen-free (SPF) young turkeys. Importantly, turkeys vaccinated with these MTase-defective raMPVs triggered a high level of neutralizing antibody and were completely protected from challenge with homologous aMPV Colorado strain and heterologous aMPV Minnesota strain. Collectively, our results indicate (i) that aMPV lacking 2'-O methylation is highly attenuated in vitro and in vivo and (ii) that inhibition of mRNA cap MTase can serve as a novel target to rationally design live attenuated vaccines for aMPV and perhaps other paramyxoviruses. IMPORTANCE:Paramyxoviruses include many economically and agriculturally important viruses such as avian metapneumovirus (aMPV), and Newcastle disease virus (NDV), human pathogens such as human respiratory syncytial virus, human metapneumovirus, human parainfluenza virus type 3, and measles virus, and highly lethal emerging pathogens such as Nipah virus and Hendra virus. For many of them, there is no effective vaccine or antiviral drug. These viruses share common strategies for viral gene expression and replication. During transcription, paramyxoviruses produce capped, methylated, and polyadenylated mRNAs. Using aMPV as a model, we found that viral ribose 2'-O methyltransferase (MTase) is a novel approach to rationally attenuate the virus for vaccine purpose. Recombinant aMPV (raMPV) lacking 2'-O MTase were not only highly attenuated in turkeys but also provided complete protection against the challenge of homologous and heterologous aMPV strains. This novel approach can be applicable to other animal and human paramyxoviruses for rationally designing live attenuated vaccines.
journal_name
J Viroljournal_title
Journal of virologyauthors
Sun J,Wei Y,Rauf A,Zhang Y,Ma Y,Zhang X,Shilo K,Yu Q,Saif YM,Lu X,Yu L,Li Jdoi
10.1128/JVI.01095-14subject
Has Abstractpub_date
2014-11-01 00:00:00pages
12348-63issue
21eissn
0022-538Xissn
1098-5514pii
JVI.01095-14journal_volume
88pub_type
杂志文章abstract::In varicella-zoster virus (VZV)-infected primary human brain vascular adventitial fibroblasts (BRAFs), levels of beta interferon (IFN-β,) STAT1, and STAT2 transcripts as well as STAT1 and STAT2 protein were decreased. IFN-α transcript levels were increased but not secreted IFN-α protein levels. Compared to IFN-α-treat...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.01945-14
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doi:10.1128/JVI.49.2.591-593.1984
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doi:10.1128/JVI.00704-09
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pub_type: 杂志文章
doi:10.1128/JVI.71.1.34-41.1997
更新日期:1997-01-01 00:00:00
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journal_title:Journal of virology
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pub_type: 杂志文章
doi:10.1128/JVI.66.3.1641-1648.1992
更新日期:1992-03-01 00:00:00
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pub_type: 杂志文章
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.66.4.2251-2260.1992
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pub_type: 杂志文章
doi:10.1128/JVI.6.6.865-876.1970
更新日期:1970-12-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.70.3.1695-1705.1996
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pub_type: 杂志文章
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更新日期:2005-09-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.00914-07
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.69.11.6705-6711.1995
更新日期:1995-11-01 00:00:00
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pub_type: 杂志文章
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.73.10.8898-8901.1999
更新日期:1999-10-01 00:00:00
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pub_type: 杂志文章
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.62.3.1093-1096.1988
更新日期:1988-03-01 00:00:00
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更新日期:1986-10-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/jvi.76.22.11710-11714.2002
更新日期:2002-11-01 00:00:00
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pub_type: 杂志文章
doi:10.1128/JVI.63.4.1800-1802.1989
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.75.8.3605-3612.2001
更新日期:2001-04-01 00:00:00
abstract::Purified avian myeloblastosis virus was iodinated by the lactoperoxidase method. Disruption of the labeled virions and chromatography of the viral proteins showed that radioiodine was associated only with the glycoproteins of the viral envelope. Reaction of the radiolabeled virus with antiviral antibody followed by mi...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.13.1.42-45.1974
更新日期:1974-01-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.64.3.1402-1406.1990
更新日期:1990-03-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.01495-20
更新日期:2020-12-09 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.75.4.1620-1631.2001
更新日期:2001-02-01 00:00:00