Abstract:
UNLABELLED:Infection of the lower respiratory tract by influenza A viruses results in increases in inflammation and immune cell infiltration in the lung. The dynamic relationships among the lung microenvironments, the lung, and systemic host responses during infection remain poorly understood. Here we used extensive systematic histological analysis coupled with live imaging to gain access to these relationships in ferrets infected with the 2009 H1N1 pandemic influenza A virus (H1N1pdm virus). Neutrophil levels rose in the lungs of H1N1pdm virus-infected ferrets 6 h postinfection and became concentrated at areas of the H1N1pdm virus-infected bronchiolar epithelium by 1 day postinfection (dpi). In addition, neutrophil levels were increased throughout the alveolar spaces during the first 3 dpi and returned to baseline by 6 dpi. Histochemical staining revealed that neutrophil infiltration in the lungs occurred in two waves, at 1 and 3 dpi, and gene expression within microenvironments suggested two types of neutrophils. Specifically, CCL3 levels, but not CXCL8/interleukin 8 (IL-8) levels, were higher within discrete lung microenvironments and coincided with increased infiltration of neutrophils into the lung. We used live imaging of ferrets to monitor host responses within the lung over time with [(18)F]fluorodeoxyglucose (FDG). Sites in the H1N1pdm virus-infected ferret lung with high FDG uptake had high levels of proliferative epithelium. In summary, neutrophils invaded the H1N1pdm virus-infected ferret lung globally and focally at sites of infection. Increased neutrophil levels in microenvironments did not correlate with increased FDG uptake; hence, FDG uptake may reflect prior infection and inflammation of lungs that have experienced damage, as evidenced by bronchial regeneration of tissues in the lungs at sites with high FDG levels. IMPORTANCE:Severe influenza disease is characterized by an acute infection of the lower airways that may progress rapidly to organ failure and death. Well-developed animal models that mimic human disease are essential to understanding the complex relationships of the microenvironment, organ, and system in controlling virus replication, inflammation, and disease progression. Employing the ferret model of H1N1pdm virus infection, we used live imaging and comprehensive histological analyses to address specific hypotheses regarding spatial and temporal relationships that occur during the progression of infection and inflammation. We show the general invasion of neutrophils at the organ level (lung) but also a distinct pattern of localized accumulation within the microenvironment at the site of infection. Moreover, we show that these responses were biphasic within the lung. Finally, live imaging revealed an early and sustained host metabolic response at sites of infection that may reflect damage and repair of tissues in the lungs.
journal_name
J Viroljournal_title
Journal of virologyauthors
Camp JV,Bagci U,Chu YK,Squier B,Fraig M,Uriarte SM,Guo H,Mollura DJ,Jonsson CBdoi
10.1128/JVI.00817-15subject
Has Abstractpub_date
2015-09-01 00:00:00pages
8733-48issue
17eissn
0022-538Xissn
1098-5514pii
JVI.00817-15journal_volume
89pub_type
杂志文章abstract::The unique short (Us) region of the pseudorabies virus (PRV) genome, which displays high transcriptional activity during the late phase of infection and has been found to code for glycoproteins, is partially deleted in the genomes of three vaccine strains (A57, Norden, and NIA-4). This deletion is located in the SalI ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.56.1.307-311.1985
更新日期:1985-10-01 00:00:00
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pub_type: 杂志文章
doi:10.1128/JVI.70.1.663-666.1996
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.62.3.1055-1056.1988
更新日期:1988-03-01 00:00:00
abstract::The use of adenovirus vectors for human gene therapy is limited by potent inflammatory responses that result in significant morbidity. In kidney-derived epithelial cells (REC), activation of extracellular signal-regulated kinase 1/2 (ERK) and p38 kinase (p38) pathways occurred within 20 min of transduction with the se...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/jvi.76.4.1559-1568.2002
更新日期:2002-02-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.71.8.6155-6167.1997
更新日期:1997-08-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.01154-16
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.1.5.912-919.1967
更新日期:1967-10-01 00:00:00
abstract::Crimean-Congo hemorrhagic fever virus (CCHFV), a member of the genus Nairovirus of the family Bunyaviridae, causes severe disease with high rates of mortality in humans. The CCHFV M RNA segment encodes the virus glycoproteins G(N) and G(C). To understand the processing and intracellular localization of the CCHFV glyco...
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pub_type: 杂志文章
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更新日期:2005-05-01 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.02215-20
更新日期:2020-12-02 00:00:00
abstract:UNLABELLED:Airway epithelium is the primary target of many respiratory viruses. However, virus induction and antagonism of host responses by human airway epithelium remains poorly understood. To address this, we developed a model of respiratory syncytial virus (RSV) infection based on well-differentiated pediatric prim...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.02119-15
更新日期:2015-12-01 00:00:00
abstract::A member of the family Circoviridae, porcine circovirus type 2 (PCV2), is associated with postweaning multisystemic wasting syndrome (PMWS), a recent emerging disease worldwide. PCV2 is also found in clinically asymptomatic animals. This paradoxical finding makes the syndrome etiology challenging. We developed new ass...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.05156-11
更新日期:2011-11-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.00844-17
更新日期:2017-09-12 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.63.9.3974-3982.1989
更新日期:1989-09-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.00342-11
更新日期:2011-06-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.00406-07
更新日期:2007-07-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.02433-10
更新日期:2011-07-01 00:00:00
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pub_type: 杂志文章
doi:10.1128/JVI.19.2.490-494.1976
更新日期:1976-08-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
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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.76.17.8702-8709.2002
更新日期:2002-09-01 00:00:00
abstract::H9N2 influenza viruses are panzootic in domestic poultry in Eurasia and since 1999 have caused transient infections in humans and pigs. To investigate the zoonotic potential of H9N2 viruses, we studied the evolution of the viruses in live-poultry markets in Hong Kong in 2003. H9N2 was the most prevalent influenza viru...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.78.16.8609-8614.2004
更新日期:2004-08-01 00:00:00
abstract::Polyacrylamide gel electrophoresis and tryptic peptide fingerprint analysis of the proteins made in a cell-free system derived from L-cells and immunoprecipitated with simian virus 40 (SV40) anti-T serum demonstrated that both SV40 large-T and small-T antigens are synthesized in vitro in response to mRNA isolated from...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.28.1.154-170.1978
更新日期:1978-10-01 00:00:00
abstract::Ebola virus (EBOV) causes severe hemorrhagic fever, for which therapeutic options are not available. Preventing the entry of EBOV into host cells is an attractive antiviral strategy, which has been validated for HIV by the FDA approval of the anti-HIV drug enfuvirtide. To identify inhibitors of EBOV entry, the EBOV en...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.01456-10
更新日期:2011-04-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.03239-12
更新日期:2013-04-01 00:00:00
abstract::Several domains of CD4 have been suggested to play a critical role in events that follow its binding to the human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein (gp120-gp41). It has been reported previously that cells expressing a chimeric molecule consisting of the first 177 residues of human CD4 attache...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.67.11.6469-6475.1993
更新日期:1993-11-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.80.6.3009-3020.2006
更新日期:2006-03-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.37.1.156-160.1981
更新日期:1981-01-01 00:00:00
abstract::To study the expression of the Autographa californica nuclear polyhedrosis virus (AcNPV) genome, intracellular virus-specific proteins and mRNAs were pulsed-labeled, extracted, and analyzed at 6-h intervals during the replicative cycle. Most RNAs were detected between 12 and 24 h postinfection (p.i.), but many continu...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.50.3.739-747.1984
更新日期:1984-06-01 00:00:00
abstract::The present study used the cottontail rabbit papillomavirus DNA-rabbit system to evaluate whether the regulatory genes E1 and E2 and the transforming gene E6 are required for papilloma formation. Frameshift mutations were generated in the individual genes in the context of a full-length cottontail rabbit papillomaviru...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.68.9.6097-6102.1994
更新日期:1994-09-01 00:00:00