Abstract:
:Seasonal influenza viruses are a major cause of human disease worldwide. Most neutralizing antibodies (Abs) elicited by influenza viruses target the head domain of the hemagglutinin (HA) protein. Anti-HA head Abs can be highly potent, but they have limited breadth since the HA head is variable. There is great interest in developing new universal immunization strategies that elicit broadly neutralizing Abs against conserved regions of HA, such as the stalk domain. Although HA stalk Abs can provide protection in animal models, it is unknown if they are present at sufficient levels in humans to provide protection against naturally acquired influenza virus infections. Here, we quantified H1N1 HA head- and stalk-specific Abs in 179 adults hospitalized during the 2015-2016 influenza virus season. We found that HA head Abs, as measured by hemagglutinin inhibition (HAI) assays, were associated with protection against naturally acquired H1N1 infection. HA stalk-specific serum total IgG titers were also associated with protection, but this association was attenuated and not statistically significant after adjustment for HA head-specific Ab titers. We found slightly higher titers of HA stalk-specific IgG1 and IgA Abs in sera from uninfected participants than in sera from infected participants; however, we found no difference in serum in vitro antibody-dependent cellular cytotoxicity activity. In passive transfer experiments, sera from participants with high HAI activity efficiently protected mice, while sera with low HAI activity protected mice to a lower extent. Our data suggest that HA head Abs are more efficient at protecting against H1N1 infection than HA stalk Abs.IMPORTANCE Abs targeting the HA head of influenza viruses are often associated with protection from influenza virus infections. These Abs typically have limited breadth, since mutations frequently arise in HA head epitopes. New vaccines targeting the more conserved HA stalk domain are being developed. Abs that target the HA stalk are protective in animal models, but it is unknown if these Abs exist at protective levels in humans. Here, we completed experiments to determine if Abs against the HA head and stalk were associated with protection from naturally acquired human influenza virus infections during the 2015-2016 influenza season.
journal_name
J Viroljournal_title
Journal of virologyauthors
Christensen SR,Toulmin SA,Griesman T,Lamerato LE,Petrie JG,Martin ET,Monto AS,Hensley SEdoi
10.1128/JVI.02134-18subject
Has Abstractpub_date
2019-04-03 00:00:00issue
8eissn
0022-538Xissn
1098-5514pii
JVI.02134-18journal_volume
93pub_type
临床试验,杂志文章,多中心研究abstract::While a diversity of immunogens that elicit qualitatively different cellular immune responses are being assessed in clinical human immunodeficiency virus vaccine trials, the consequences of those varied responses for viral control remain poorly understood. In the present study, we evaluated the induction of virus-spec...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.00204-08
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abstract::YY1 is a zinc finger transcription factor which acts as either a repressor or an activator dependent on the promoter context. YY1 is a potent activator of the genuine human papillomavirus type 18 (HPV-18) upstream regulatory region (URR) in HeLa cells, which are known for high-level expression of the HPV-18 early gene...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.69.1.1-12.1995
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.73.3.2541-2546.1999
更新日期:1999-03-01 00:00:00
abstract::After incubation at 37 C for 2 or more days, Basal Medium Eagle (BME) supplemented with 25% fetal calf serum (FCS) was not able to support adequate growth of EB3 and other lines of Burkitt tumor cells. The medium did, however, increase, by a factor of about 10, the number of cells synthesizing herpes-type virus with w...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.2.3.182-191.1968
更新日期:1968-03-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.00573-16
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.66.2.766-772.1992
更新日期:1992-02-01 00:00:00
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pub_type: 杂志文章
doi:10.1128/jvi.78.6.2808-2818.2004
更新日期:2004-03-01 00:00:00
abstract::The human herpesvirus entry mediator C (HveC), also known as the poliovirus receptor-related protein 1 (PRR1) and as nectin-1, allows the entry of herpes simplex virus type 1 (HSV-1) and HSV-2 into mammalian cells. The interaction of virus envelope glycoprotein D (gD) with such a receptor is an essential step in the p...
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更新日期:2000-12-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.66.2.906-913.1992
更新日期:1992-02-01 00:00:00
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pub_type: 杂志文章
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abstract::The initiation of human immunodeficiency virus type 1 (HIV-1) reverse transcription occurs at a site in the viral RNA genome which is designated the primer-binding site (PBS). The HIV-1 PBS is an 18-nucleotide sequence that is complementary to the 3'-terminal 18 nucleotides of tRNA(3Lys), which is used as the primer f...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.69.10.6021-6029.1995
更新日期:1995-10-01 00:00:00
abstract:UNLABELLED:Cell culture systems reproducing virus replication can serve as unique models for the discovery of novel bioactive molecules. Here, using a hepatitis C virus (HCV) cell culture system, we identified neoechinulin B (NeoB), a fungus-derived compound, as an inhibitor of the liver X receptor (LXR). NeoB was init...
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pub_type: 杂志文章
doi:10.1128/JVI.00856-16
更新日期:2016-09-29 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.01690-08
更新日期:2009-03-01 00:00:00
abstract::Mice were infected with lymphocytic choriomeningitis virus and injected once 24 h later with a monoclonal antibody directed against gamma interferon. In comparison with controls, the increase of numbers of CD8+ T cells and the generation of virus-specific cytotoxic T lymphocytes in spleens and virus clearance from org...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.70.3.1521-1526.1996
更新日期:1996-03-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.44.3.804-812.1982
更新日期:1982-12-01 00:00:00
abstract::Barley stripe mosaic virus (BSMV) encodes three movement proteins in an overlapping triple gene block (TGB), but little is known about the physical interactions of these proteins. We have characterized a ribonucleoprotein (RNP) complex consisting of the TGB1 protein and plus-sense BSMV RNAs from infected barley plants...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.02586-07
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.61.3.845-850.1987
更新日期:1987-03-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.66.9.5682-5684.1992
更新日期:1992-09-01 00:00:00
abstract::Due to increasing concerns about human infection by various H7 influenza viruses, including recent H7N9 viruses, we evaluated the genetic relationships and cross-protective efficacies of three different Eurasian H7 avian influenza viruses. Phylogenic and molecular analyses revealed that recent Eurasian H7 viruses can ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.02259-16
更新日期:2017-05-12 00:00:00
abstract::The C-terminal domain of human immunodeficiency virus type 1 (HIV-1) integrase (IN) is a dimer that binds to DNA in a nonspecific manner. The structure of the minimal region required for DNA binding (IN220-270) has been solved by nuclear magnetic resonance spectroscopy. The overall fold of the C-terminal domain of HIV...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.72.6.4841-4848.1998
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.64.5.2117-2125.1990
更新日期:1990-05-01 00:00:00
abstract::Apoptosis of virus-infected cells occurs either as a direct response to viral infection or upon recognition of infection by the host immune response. Apoptosis reduces production of new virus from these cells, and therefore viruses have evolved inhibitory mechanisms. We previously showed that laboratory strains of her...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.73.11.8950-8957.1999
更新日期:1999-11-01 00:00:00
abstract::Phosphorylation of viral proteins plays important roles in the influenza A virus (IAV) life cycle. By using mass spectrometry, we identified tyrosine 132 (Y132) as a phosphorylation site of the matrix protein (M1) of the influenza virus A/WSN/1933(H1N1). Phosphorylation at this site is essential to the process of viru...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.03024-12
更新日期:2013-06-01 00:00:00
abstract::AIDS vaccination has a pressing need for more potent vaccination vectors capable of eliciting strong, diversified, and long-lasting cellular immune responses against human immunodeficiency virus (HIV). Lentiviral vectors have demonstrated efficiency not only as gene delivery vehicles for gene therapy applications but ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.01284-09
更新日期:2009-11-01 00:00:00
abstract::Earlier studies have shown that herpes simplex viruses adsorb to but do not penetrate permissive baby hamster kidney clonal cell lines designated the BJ series and constitutively expressing the herpes simplex virus 1 (HSV-1) glycoprotein D (gD). To investigate the mechanism of the restriction, the following steps were...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.64.12.6070-6079.1990
更新日期:1990-12-01 00:00:00
abstract::Caprine arthritis encephalitis virus (CAEV) is a lentivirus closely related to visna virus and more distantly to other lentiviruses, such as human immunodeficiency virus. The genomes of visna virus and CAEV contain a tat gene encoding a protein able to weakly transactivate its own long terminal repeat, suggesting that...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.69.9.5445-5454.1995
更新日期:1995-09-01 00:00:00
abstract::Current human immunodeficiency virus type 1 (HIV-1) envelope vaccine candidates elicit high antibody binding titers with neutralizing activity against T-cell line-adapted but not primary HIV-1 isolates. Serum antibodies from these human vaccine recipients were also found to be preferentially directed to linear epitope...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.71.6.4319-4330.1997
更新日期:1997-06-01 00:00:00
abstract::Virus-specific CD4(+) T-cell function is thought to play a central role in induction and maintenance of effective CD8(+) T-cell responses in experimental animals or humans. However, the reasons that diminished proliferation of human immunodeficiency virus (HIV)-specific CD4(+) T cells is observed in the majority of in...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/jvi.77.20.10900-10909.2003
更新日期:2003-10-01 00:00:00
abstract::Gene therapy is proposed as a novel therapeutic strategy for treating glioblastoma multiforme (GBM), a devastating brain cancer. In the clinic, antivector immune responses pose formidable challenges. Herein we demonstrate that high-capacity adenovirus vectors (HC-Ads) carrying the conditional cytotoxic gene herpes sim...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.00232-08
更新日期:2008-05-01 00:00:00
abstract::Echovirus 1 (EV1) is a human pathogen which belongs to the Picornaviridae family of RNA viruses. We have analyzed the early events of infection after EV1 binding to its receptor alpha 2 beta 1 integrin and elucidated the route by which EV1 gains access to the host cell. EV1 binding onto the cell surface and subsequent...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/jvi.76.4.1856-1865.2002
更新日期:2002-02-01 00:00:00