Hyporeactivity of Alveolar Macrophages and Higher Respiratory Cell Permissivity Characterize DBA/2J Mice Infected by Influenza A Virus

Casanova, Tomás; Paar, Els Van de; Desmecht, Daniël; Garigliany, Mutien-Marie

doi:10.1089/jir.2014.0237

Cited by 14 publications

(17 citation statements)

References 35 publications

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“…However, this phenotype was not associated with a higher viral load; in fact, the HA190 mutant and the double mutant showed the lowest virus titers in mouse lungs. This effect may be explained by an enhanced inflammatory response that impairs virus replication and, in the case of the HA190ϩHA212 mutant, results in increased pathogenicity (52)(53)(54). The murine airway epithelium is known to contain predominantly ␣2,3-linked sialic acids (55).…”

Section: Discussionmentioning

confidence: 99%

Mutations during the Adaptation of H9N2 Avian Influenza Virus to the Respiratory Epithelium of Pigs Enhance Sialic Acid Binding Activity and Virulence in Mice

Yang

Punyadarsaniya

Lambertz

et al. 2017

J Virol

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The natural reservoir for influenza viruses is waterfowl, and from there they succeeded in crossing the barrier to different mammalian species. We analyzed the adaptation of avian influenza viruses to a mammalian host by passaging an H9N2 strain three times in differentiated swine airway epithelial cells. Using precisioncut slices from the porcine lung to passage the parental virus, isolates from each of the three passages (P1 to P3) were characterized by assessing growth curves and ciliostatic effects. The only difference noted was an increased growth kinetics of the P3 virus. Sequence analysis revealed four mutations: one each in the PB2 and NS1 proteins and two in the HA protein. The HA mutations, A190V and T212I, were characterized by generating recombinant viruses containing either one or both amino acid exchanges. Whereas the parental virus recognized ␣2,3-linked sialic acids preferentially, the HA190 mutant bound to a broad spectrum of glycans with ␣2,6/8/9-linked sialic acids. The HA212 mutant alone differed only slightly from the parental virus; however, the combination of both mutations (HA190ϩHA212) increased the binding affinity to those glycans recognized by the HA190 mutant. Remarkably, only the HA double mutant showed a significantly increased pathogenicity in mice. In contrast, none of those mutations affected the ciliary activity of the epithelial cells which is characteristic for virulent swine influenza viruses. Taken together, our results indicate that shifts in the HA receptor affinity are just an early adaptation step of avian H9N2 strains; further mutational changes may be required to become virulent for pigs.IMPORTANCE Swine play an important role in the interspecies transmission of influenza viruses. Avian influenza A viruses (IAV) of the H9N2 subtype have successfully infected hosts from different species but have not established a stable lineage. We have analyzed the adaptation of IAV-H9N2 virus to target cells of a new host by passaging the virus three times in differentiated porcine respiratory epithelial cells. Among the four mutations detected, the two HA mutations were analyzed by generating recombinant viruses. Depending on the infection system used, the mutations differed in their phenotypic expression, e.g., sialic acid binding activity, replication kinetics, plaque size, and pathogenicity in inbred mice. However, none of the mutations affected the ciliary activity which serves as a virulence marker. Thus, early

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Section: Discussionmentioning

confidence: 99%

Mutations during the Adaptation of H9N2 Avian Influenza Virus to the Respiratory Epithelium of Pigs Enhance Sialic Acid Binding Activity and Virulence in Mice

Yang

Punyadarsaniya

Lambertz

et al. 2017

J Virol

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“…In the alveolar space, the virus is picked up by alveolar macrophages and, together with intense phagocytic activity, it generates a swift inflammatory response. 2,12 Through immunohistochemical staining, experimental infections in mice and pigs have shown that viral antigens are mainly detected in the epithelium of the airways and in alveolar macrophages, which have presented systematically higher immunoreactivity. [12][13][14] Through IHC, we detected positivity towards infection by SIV in a natural presentation of a field virus, by using this technique as a rapid tool with in situ precision and reduced costs for the detection of this disease.…”

Section: Discussionmentioning

confidence: 99%

“…2,12 Through immunohistochemical staining, experimental infections in mice and pigs have shown that viral antigens are mainly detected in the epithelium of the airways and in alveolar macrophages, which have presented systematically higher immunoreactivity. [12][13][14] Through IHC, we detected positivity towards infection by SIV in a natural presentation of a field virus, by using this technique as a rapid tool with in situ precision and reduced costs for the detection of this disease. Additionally, Capuccio 15 evidenced differences between the intensity and distribution of the viral antigen in the lungs depending on which SIV strain was present and on the stage of infection, suggesting a new approach for greater precision in the etiological diagnosis of SIV that would complement molecular techniques with IHC.…”

Section: Discussionmentioning

confidence: 99%

Immunohistochemistry: A Rapid and Specific Diagnostic Tool for Influenza Virus Infection in Pigs

Casanova¹,

Rojas²,

Baeza³

et al. 2017

JDVAR

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During the 2016 spring, a local outbreak of severe dyspnea, seromucous nasal secretion, anorexia and loss of productive performance was identified in an intensive pig farm in southern Chile. Samples of diseased animals were submitted to the Diagnostic Laboratory of the Faculty of Veterinary Medicine, in Chillan, Chile, for pathological and histopathological study. Macroscopically, lungs appeared to be congested, edematous and "non-collapsed", which could be related to lesions compatible with interstitial pneumonia. Microscopic lesions showed a variable thickening of the septa, epithelial necrosis of the airways, diffuse inflammatory infiltration surrounding bronchial and bronchiolar areas, inflammatory exudate in the alveolar spaces with activate alveolar macrophages and fibrin. All lesions were compatible with Swine Influenza Virus (SIV) infection, and we successfully confirmed through SIV nucleoprotein immuno histochemistry staining of said samples, by utilizing a rapid and specific first-line diagnostic method that allows a rapid decision-making tool to control the spread of the virus. Additionally, the presence of the virus was confirmed by a serological field study.

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“…injection of Ketamine (80 mg/kg) and Xylazine (10 mg/kg). Frozen virus aliquots were thawed, centrifuged for 5 min at 2,500 g, washed and diluted to a non-lethal dose in C57BL6 strain [9 plaque forming unit (pfu)] in sterile DPBS ( 31 ). For infection, 30 μl of H1N1 virus or DPBS were inoculated via i.n.…”

Section: Animals and Methodsmentioning

confidence: 99%

Growth Hormone (GH) Deficient Mice With GHRH Gene Ablation Are Severely Deficient in Vaccine and Immune Responses Against Streptococcus pneumoniae

et al. 2018

Self Cite

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The precise impact of the somatotrope axis upon the immune system is still highly debated. We have previously shown that mice with generalized ablation of growth hormone (GH) releasing hormone (GHRH) gene (Ghrh−/−) have normal thymus and T-cell development, but present a marked spleen atrophy and B-cell lymphopenia. Therefore, in this paper we have investigated vaccinal and anti-infectious responses of Ghrh−/− mice against S. pneumoniae, a pathogen carrying T-independent antigens. Ghrh−/− mice were unable to trigger production of specific IgM after vaccination with either native pneumococcal polysaccharides (PPS, PPV23) or protein-PPS conjugate (PCV13). GH supplementation of Ghrh−/− mice restored IgM response to PPV23 vaccine but not to PCV13 suggesting that GH could exert a specific impact on the spleen marginal zone that is strongly implicated in T-independent response against pneumococcal polysaccharides. As expected, after administration of low dose of S. pneumoniae, wild type (WT) completely cleared bacteria after 24 h. In marked contrast, Ghrh−/− mice exhibited a dramatic susceptibility to S. pneumoniae infection with a time-dependent increase in lung bacterial load and a lethal bacteraemia already after 24 h. Lungs of infected Ghrh−/− mice were massively infiltrated by inflammatory macrophages and neutrophils, while lung B cells were markedly decreased. The inflammatory transcripts signature was significantly elevated in Ghrh−/− mice. In this animal model, the somatotrope GHRH/GH/IGF1 axis plays a vital and unsuspected role in vaccine and immunological defense against S. pneumoniae.

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Hyporeactivity of Alveolar Macrophages and Higher Respiratory Cell Permissivity Characterize DBA/2J Mice Infected by Influenza A Virus

Cited by 14 publications

References 35 publications

Mutations during the Adaptation of H9N2 Avian Influenza Virus to the Respiratory Epithelium of Pigs Enhance Sialic Acid Binding Activity and Virulence in Mice

Mutations during the Adaptation of H9N2 Avian Influenza Virus to the Respiratory Epithelium of Pigs Enhance Sialic Acid Binding Activity and Virulence in Mice

Immunohistochemistry: A Rapid and Specific Diagnostic Tool for Influenza Virus Infection in Pigs

Growth Hormone (GH) Deficient Mice With GHRH Gene Ablation Are Severely Deficient in Vaccine and Immune Responses Against Streptococcus pneumoniae

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