Abstract:
:We have generated hexon-modified adenovirus serotype 5 (Ad5) vectors that are not neutralized by Ad5-specific neutralizing antibodies in mice. These vectors are attractive for the advancement of vaccine products because of their potential for inducing robust antigen-specific immune responses in people with prior exposure to Ad5. However, hexon-modified Ad5 vectors displayed an approximate 10-fold growth defect in complementing cells, making potential vaccine costs unacceptably high. Replacing hypervariable regions (HVRs) 1, 2, 4, and 5 with the equivalent HVRs from Ad43 was sufficient to avoid Ad5 preexisting immunity and retain full vaccine potential. However, the resulting vector displayed the same growth defect as the hexon-modified vector carrying all 9 HVRs from Ad43. The growth defect is likely due to a defect in capsid assembly, since DNA replication and late protein accumulation were normal in these vectors. We determined that the hexon-modified vectors have a 32°C cold-sensitive phenotype and selected revertants that restored vector productivity. Genome sequencing identified a single base change resulting in a threonine-to-methionine amino acid substitution at the position equivalent to residue 342 of the wild-type protein. This mutation has a suppressor phenotype (SP), since cloning it into our Ad5 vector containing all nine hypervariable regions from Ad43, Ad5.H(43m-43), increased yields over the version without the SP mutation. This growth improvement was also shown for an Ad5-based hexon-modified vector that carried the hexon hypervariable regions of Ad48, indicating that the SP mutation may have broad applicability for improving the productivity of different hexon-modified vectors.
journal_name
J Viroljournal_title
Journal of virologyauthors
Bruder JT,Chen P,Semenova E,Thomas CA,Konovalova S,Ekberg G,Ettyreddy D,McVey D,Gall JG,King CR,Brough DEdoi
10.1128/JVI.00462-13subject
Has Abstractpub_date
2013-09-01 00:00:00pages
9661-71issue
17eissn
0022-538Xissn
1098-5514pii
JVI.00462-13journal_volume
87pub_type
杂志文章abstract::Arenaviruses are negative-strand RNA viruses that cause human diseases such as lymphocytic choriomeningitis, Bolivian hemorrhagic fever, and Lassa hemorrhagic fever. No licensed vaccines exist, and current treatment is limited to ribavirin. The prototypic arenavirus, lymphocytic choriomeningitis virus (LCMV), is a mod...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.02081-10
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abstract::The herpes simplex virus type 1 (HSV-1) UL25 gene contains a 580-amino-acid open reading frame that codes for an essential protein. Previous studies have shown that the UL25 gene product is a virion component (M. A. Ali et al., Virology 216:278-283, 1996) involved in virus penetration and capsid assembly (C. Addison e...
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pub_type: 杂志文章
doi:10.1128/JVI.72.2.1060-1070.1998
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abstract::Nuclei of cells infected with Moloney murine leukemia virus (MoMuLV) were examined for the presence of gag proteins. This analysis was performed in conjunction with other studies suggesting a possible role for gag proteins in regulating nuclear events relating to processing and/or transport of viral genomic RNA. We de...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.67.3.1350-1356.1993
更新日期:1993-03-01 00:00:00
abstract::Proliferation responses of naïve CD4(+) T cells to T-cell receptor and interleukin-7 (IL-7) stimulation were evaluated by using cells from human immunodeficiency virus-positive (HIV(+)) donors. IL-7 enhanced responses to T-cell receptor stimulation, and the magnitude of this enhancement was similar in cells from healt...
journal_title:Journal of virology
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doi:10.1128/JVI.00476-07
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journal_title:Journal of virology
pub_type: 临床试验,杂志文章,多中心研究
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.72.2.1577-1585.1998
更新日期:1998-02-01 00:00:00
abstract::The ICP18.5 gene (UL28) of herpes simplex virus type 1 is a member of a well-conserved gene family among herpesviruses and is thought to play a role in localization of viral glycoproteins. We have cloned, sequenced, and expressed the entire pseudorabies virus (PRV) ICP18.5 open reading frame in Escherichia coli as a C...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.65.7.3746-3758.1991
更新日期:1991-07-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.57.3.952-959.1986
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pub_type: 杂志文章
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pub_type: 杂志文章
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更新日期:2001-06-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
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更新日期:2004-07-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
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更新日期:1967-10-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/jvi.74.17.8102-8110.2000
更新日期:2000-09-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.67.2.643-650.1993
更新日期:1993-02-01 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.63.11.4563-4568.1989
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journal_title:Journal of virology
pub_type: 杂志文章
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更新日期:2006-05-01 00:00:00
abstract::Human cytomegalovirus (HCMV) glycoprotein B (gB), encoded by the UL55 open reading frame, is an essential envelope glycoprotein involved in cell attachment and entry. Previously, we identified residue serine 900 (Ser900) as a unique site of reversible casein kinase 2 phosphorylation in the cytoplasmic domain of HCMV g...
journal_title:Journal of virology
pub_type: 杂志文章
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更新日期:2004-01-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.13.5.1134-1142.1974
更新日期:1974-05-01 00:00:00
abstract::Mounting evidence suggests that human immunodeficiency virus type 1 (HIV-1) Gag-specific T helper cells contribute to effective antiviral control, but their functional characteristics and the precise epitopes targeted by this response remain to be defined. In this study, we generated CD4(+) T-cell clones specific for ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.75.20.9771-9779.2001
更新日期:2001-10-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.67.1.548-552.1993
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abstract::At a low pH, the influenza virus hemagglutinin (HA) undergoes conformational changes that promote membrane fusion. While the critical role of fusion peptide release from the trimer interface has been demonstrated previously, the role of globular head dissociation in the overall fusion mechanism remains unclear. To inv...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.66.8.4940-4950.1992
更新日期:1992-08-01 00:00:00