Extrapulmonary tissue responses in cynomolgus macaques (Macaca fascicularis) infected with highly pathogenic avian influenza A (H5N1) virus

Tolnay, A.-E.; Baskin, Carole R.; Tumpey, Terrence M.; Sabourin, Patrick J.; Sabourin, Carol L.; Long, James P.; Pyles, John; Albrecht, Randy A.; Garcı́a-Sastre, Adolfo; Katze, Michael G.; Bielefeldt‐Ohmann, Helle

doi:10.1007/s00705-010-0662-8

Cited by 31 publications

(30 citation statements)

References 45 publications

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“…In considering other recent systems approaches to investigating the cellular course of influenza virus infection, we observe functional overlap in the categories of innate and adaptive immunity but quite limited overlap in the specific protein/genes identified in these studies (see Table S7 in the supplemental material) (18,24,27,49,55). The correlation with proteins involved in cell cycle and metabolism may represent infiltrating, activated lymphocytes and neutrophils in the alveolar spaces during viral infection (3,51) and the proliferation of local pneumocytes to repair damaged tissues. Macaque inflammatory response to influenza virus infection.…”

Section: Vol 84 2010 Macaque Response To Influenza Virus 12063mentioning

confidence: 85%

Macaque Proteome Response to Highly Pathogenic Avian Influenza and 1918 Reassortant Influenza Virus Infections

Brown

Palermo

Baskin

et al. 2010

J Virol

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The host proteome response and molecular mechanisms that drive disease in vivo during infection by a human isolate of the highly pathogenic avian influenza virus (HPAI) and 1918 pandemic influenza virus remain poorly understood. This study presents a comprehensive characterization of the proteome response in cynomolgus macaque (Macaca fascicularis) lung tissue over 7 days of infection with HPAI (the most virulent), a reassortant virus containing 1918 hemagglutinin and neuraminidase surface proteins (intermediate virulence), or a human seasonal strain (least virulent). A high-sensitivity two-dimensional liquid chromatographytandem mass spectroscopy strategy and functional network analysis were implemented to gain insight into response pathways activated in macaques during influenza virus infection. A macaque protein database was assembled and used in the identification of 35,239 unique peptide sequences corresponding to approximately 4,259 proteins. Quantitative analysis identified an increase in expression of 400 proteins during viral infection. The abundance levels of a subset of these 400 proteins produced strong correlations with disease progression observed in the macaques, distinguishing a "core" response to viral infection from a "high" response specific to severe disease. Proteome expression profiles revealed distinct temporal response kinetics between viral strains, with HPAI inducing the most rapid response. While proteins involved in the immune response, metabolism, and transport were increased rapidly in the lung by HPAI, the other viruses produced a delayed response, characterized by an increase in proteins involved in oxidative phosphorylation, RNA processing, and translation. Proteomic results were integrated with previous genomic and pathological analysis to characterize the dynamic nature of the influenza virus infection process.

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Section: Vol 84 2010 Macaque Response To Influenza Virus 12063mentioning

confidence: 85%

Macaque Proteome Response to Highly Pathogenic Avian Influenza and 1918 Reassortant Influenza Virus Infections

Brown

Palermo

Baskin

et al. 2010

J Virol

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“…Rabbit anti-GFAP (Dako) and goat anti-Iba1 (Abcam) antibodies were used to assess astrocytic and microglial activation in brain and spinal cord sections, using a previously described protocol (Miura et al, 2008). The degree of viral antigen load and glial cell activation was scored semiquantitatively as described previously (Bielefeldt-Ohmann et al, 2012;Tolnay et al, 2010) by an observer (H. B.-O.)…”

Section: Methodsmentioning

confidence: 99%

End-point disease investigation for virus strains of intermediate virulence as illustrated by flavivirus infections

Suen

Prow

Setoh

et al. 2016

Journal of General Virology

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“…The degree of viral antigen load and glial cell activation was scored semi-quantitatively as previously described [72,256] …”

Section: Immunohistochemistrymentioning

confidence: 99%

“…Immunophenotyping of rabbit T lymphocytes and histiocytes in inflammatory aggregates was achieved using cross-reactive anti-human CD3 (CD3 clone F7.2.38, Dako) and anti-human myeloid/histiocytic antigen (Clone MAC387, Dako) mouse monoclonal antibodies, respectively, using previously described protocols [256]. For each IHC batch, a positive and negative antigen control was included.…”

Section: Immunohistochemistry (Ihc)mentioning

confidence: 99%

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Investigation of neuropathogenesis and control of an equine-pathogenic Australian West Nile virus isolate in an established CD1 Swiss white mouse and a novel rabbit model

Suen¹

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West Nile virus (WNV) is a globally significant mosquito-borne neurotropic virus. In 2011, a large-scale arboviral encephalitis outbreak occurred in Australia, involving close to 1000 horses. A virulent WNV strain, WNV NSW2011 , was isolated from the brain of an encephalitic horse during this outbreak. Preliminary assessment showed that this strain is intermediate in virulence and belongs in the same lineage as the highly virulent North American strains. However, the pathogenesis of WNV in general, let alone this novel Australian strain, remains largely unclear.The first part of the project aimed to investigate the pathogenesis of lethal WNV NSW2011 infection in the established young adult Swiss white (CD1) mouse model, since previous survival challenge experiments demonstrated high lethality (~70%) of WNV NSW2011 in this animal model. I conducted a pilot time-course experiment, which demonstrated only benign pathological and virological outcomes in sacrificed mice on day 3 and 7 post-infection (pi), despite the relatively high lethality seen in previous survival trials. In a subsequent experiment, I characterised the disease phenotype in moribund/dead and surviving mice after WNV NSW2011 infection. Notably, I detected a high degree of intra-group variability in the neuropathology, neural infection and glial cell activation. Even cases with neuroinvasion are typically not fatal, unless underlying co-morbidities or immunosuppressive disease exist.I chose rabbits as a candidate for a novel animal model, due to the ease of performing intra-vital sampling and monitoring, as well as the possibility for tissue sharing in different assays, given the larger size of rabbits than mice. Rabbits are also hind-gut fermenters, and thus may be a better representation of a horse than a mouse. New Zealand White (NZWRs; Oryctolagus cuniculus) and iii North American cottontail rabbits (CTRs; Sylvilagus sp.) were challenged with WNV strains of different virulence (WNV NSW2011 and WNV TX8667 ), and the prototype Murray Valley encephalitis virus strain (MVE 1-51 ), by the footpad route. The rabbits were consistently resistant to developing severe disease after virulent WNV and MVEV infection, regardless of age, gender and species, despite productive virus replication in the draining popliteal lymph node (PLN). The resultant viraemia for all rabbits was also of low magnitude and transient. Furthermore, establishment of virus infection in the brain was not a feature of the disease, despite mild to moderate neuropathology in a subset of rabbits. This capacity to control flavivirus infection may be explained by the rapid antiviral innate immune response detectable by day 3 pi, as well as a fast anti-WNV neutralising antibody response detectable from day 7 pi.Comparisons of the tissue-specific transcriptional profile of important cytokine and chemokine genes suggested that virus control in rabbits was achieved differently depending on the virus, as well as the rabbit species. However, common transcriptional upregulation of IFNγ in...

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Extrapulmonary tissue responses in cynomolgus macaques (Macaca fascicularis) infected with highly pathogenic avian influenza A (H5N1) virus

Cited by 31 publications

References 45 publications

Macaque Proteome Response to Highly Pathogenic Avian Influenza and 1918 Reassortant Influenza Virus Infections

Macaque Proteome Response to Highly Pathogenic Avian Influenza and 1918 Reassortant Influenza Virus Infections

End-point disease investigation for virus strains of intermediate virulence as illustrated by flavivirus infections

Investigation of neuropathogenesis and control of an equine-pathogenic Australian West Nile virus isolate in an established CD1 Swiss white mouse and a novel rabbit model

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