Complicated Secondary Pneumonia after Swine-Origin Influenza A Virus Infection in an Immunocompetent Patient

Igusa, Ryotaro; Sakakibara, Tomohiro; Shibahara, Taizo; Sakamoto, Kazuhiro; Nishimura, Hidekazu; Ota, Kozo

doi:10.1620/tjem.226.117

Cited by 6 publications

(5 citation statements)

References 7 publications

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“…We observed extreme phenotypes in weight loss and survival among the CC founder strains, similar to that reported in previous studies of mouse genetic regulation of IAV pathogenesis (Ferris et al 2013) and immune cell associations (Phillippi et al 2014) using incipient CC lines. The diversity of phenotypes observed in these studies mimics the diverse clinical symptoms of patients infected with either IAV or SARS-CoV (Pabst et al 2011; Igusa et al 2012; Zaas et al 2009). …”

Section: Discussionmentioning

confidence: 67%

Genomic Profiling of Collaborative Cross Founder Mice Infected with Respiratory Viruses Reveals Novel Transcripts and Infection-Related Strain-Specific Gene and Isoform Expression

Xiong

Morrison

Ferris

et al. 2014

G3 Genes|Genomes|Genetics

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Genetic variation between diverse mouse species is well-characterized, yet existing knowledge of the mouse transcriptome comes largely from one mouse strain (C57BL/6J). As such, it is unlikely to reflect the transcriptional complexity of the mouse species. Gene transcription is dynamic and condition-specific; therefore, to better understand the mouse transcriptional response to respiratory virus infection, we infected the eight founder strains of the Collaborative Cross with either influenza A virus or severe acute respiratory syndrome coronavirus and sequenced lung RNA samples at 2 and 4 days after infection. We found numerous instances of transcripts that were not present in the C57BL/6J reference annotation, indicating that a nontrivial proportion of the mouse genome is transcribed but poorly annotated. Of these novel transcripts, 2150 could be aligned to human or rat genomes, but not to existing mouse genomes, suggesting functionally conserved sequences not yet recorded in mouse genomes. We also found that respiratory virus infection induced differential expression of 4287 splicing junctions, resulting in strain-specific isoform expression. Of these, 59 were influenced by strain-specific mutations within 2 base pairs of key intron–exon boundaries, suggesting cis-regulated expression. Our results reveal the complexity of the transcriptional response to viral infection, previously undocumented genomic elements, and extensive diversity in the response across mouse strains. These findings identify hitherto unexplored transcriptional patterns and undocumented transcripts in genetically diverse mice. Host genetic variation drives the complexity and diversity of the host response by eliciting starkly different transcriptional profiles in response to a viral infection.

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Section: Discussionmentioning

confidence: 67%

Genomic Profiling of Collaborative Cross Founder Mice Infected with Respiratory Viruses Reveals Novel Transcripts and Infection-Related Strain-Specific Gene and Isoform Expression

Xiong

Morrison

Ferris

et al. 2014

G3 Genes|Genomes|Genetics

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“…Animals [8][9][10][11][12][13][14][15][16] week old female animals from the 8 founder strains (A/ J, C57BL/6J, 129S1/SvImJ, NOD/ShiLtJ, NZO/HILtJ, CAST/EiJ, PWK/PhJ, and WSB/EiJ) were derived from the Jackson labs (jax.org), and bred at UNC Chapel Hill under specific pathogen free conditions. 8-12 week old female Pre-CC mice were bred at Oak Ridge National Laboratories under specific pathogen free conditions, and transferred directly into a BSL-3 containment laboratory at UNC Chapel Hill.…”

Section: Ethics Statementmentioning

confidence: 99%

“…Among infected individuals there is significant variation in the clinical disease caused by IAV ranging from an asymptomatic infection to severe and acute respiratory distress syndrome [2][3][4][5][6][7][8]. Population-wide disease variation applies not only to clinical disease, but also to individual immune responses mounted in response to IAV infection [9,10], as well as long-term complicating pathologies and co-infections [2,[11][12][13]. Despite the importance of understanding the underlying mechanisms of IAV-associated disease, the sources of the observed disease variation are unclear.…”

Section: Introductionmentioning

confidence: 99%

Modeling Host Genetic Regulation of Influenza Pathogenesis in the Collaborative Cross

et al. 2013

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Genetic variation contributes to host responses and outcomes following infection by influenza A virus or other viral infections. Yet narrow windows of disease symptoms and confounding environmental factors have made it difficult to identify polymorphic genes that contribute to differential disease outcomes in human populations. Therefore, to control for these confounding environmental variables in a system that models the levels of genetic diversity found in outbred populations such as humans, we used incipient lines of the highly genetically diverse Collaborative Cross (CC) recombinant inbred (RI) panel (the pre-CC population) to study how genetic variation impacts influenza associated disease across a genetically diverse population. A wide range of variation in influenza disease related phenotypes including virus replication, virus-induced inflammation, and weight loss was observed. Many of the disease associated phenotypes were correlated, with viral replication and virus-induced inflammation being predictors of virus-induced weight loss. Despite these correlations, pre-CC mice with unique and novel disease phenotype combinations were observed. We also identified sets of transcripts (modules) that were correlated with aspects of disease. In order to identify how host genetic polymorphisms contribute to the observed variation in disease, we conducted quantitative trait loci (QTL) mapping. We identified several QTL contributing to specific aspects of the host response including virus-induced weight loss, titer, pulmonary edema, neutrophil recruitment to the airways, and transcriptional expression. Existing whole-genome sequence data was applied to identify high priority candidate genes within QTL regions. A key host response QTL was located at the site of the known anti-influenza Mx1 gene. We sequenced the coding regions of Mx1 in the eight CC founder strains, and identified a novel Mx1 allele that showed reduced ability to inhibit viral replication, while maintaining protection from weight loss.

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“…Type II pneumocytes were considered the main target of influenza A/H1N1 infection [ 5 ]. A limited number of observations described in vivo samples, such as bronchoalveolar lavage (BAL) [ 6 – 8 ]. BAL may be useful for cytological analysis in influenza virus pneumonias.…”

Section: Introductionmentioning

confidence: 99%

Influenza A/H1N1 Severe Pneumonia: Novel Morphocytological Findings in Bronchoalveolar Lavage

Faverio

Aliberti

Ezekiel

et al. 2014

Interdisciplinary Perspectives on Infectious Diseases

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We present the results of bronchoalveolar lavage (BAL) performed in three patients with severe influenza A/H1N1 pneumonia complicated by acute respiratory distress syndrome (ARDS). Light microscopy analysis of BAL cytocentrifugates showed the presence of characteristic large, mononuclear, plasmoblastic/plasmocytoid-like cells never described before. Via transmission electron microscopy, these cells were classified as atypical type II pneumocytes and some of them showed cytoplasmic vesicles and inclusions. We concluded that plasmoblastic/plasmocytoid-like type II pneumocytes might represent a morphologic marker of A/H1N1 influenza virus infection as well as reparative cellular activation after diffuse alveolar damage.

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Complicated Secondary Pneumonia after Swine-Origin Influenza A Virus Infection in an Immunocompetent Patient

Cited by 6 publications

References 7 publications

Genomic Profiling of Collaborative Cross Founder Mice Infected with Respiratory Viruses Reveals Novel Transcripts and Infection-Related Strain-Specific Gene and Isoform Expression

Genomic Profiling of Collaborative Cross Founder Mice Infected with Respiratory Viruses Reveals Novel Transcripts and Infection-Related Strain-Specific Gene and Isoform Expression

Modeling Host Genetic Regulation of Influenza Pathogenesis in the Collaborative Cross

Influenza A/H1N1 Severe Pneumonia: Novel Morphocytological Findings in Bronchoalveolar Lavage

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