Dataset Information

The tree shrew is a promising model for the study of influenza B virus infection.

ABSTRACT:

Background

Influenza B virus is a main causative pathogen of annual influenza epidemics, however, research on influenza B virus in general lags behind that on influenza A viruses, one of the important reasons is studies on influenza B viruses in animal models are limited. Here we investigated the tree shrew as a potential model for influenza B virus studies.

Methods

Tree shrews and ferrets were inoculated with either a Yamagata or Victoria lineage influenza B virus. Symptoms including nasal discharge and weight loss were observed. Nasal wash and respiratory tissues were collected at 2, 4 and 6 days post inoculation (DPI). Viral titers were measured in nasal washes and tissues were used for pathological examination and extraction of mRNA for measurement of cytokine expression.

Results

Clinical signs and pathological changes were also evident in the respiratory tracts of tree shrews and ferrets. Although nasal symptoms including sneezing and rhinorrhea were evident in ferrets infected with influenza B virus, tree shrews showed no significant respiratory symptoms, only milder nasal secretions appeared. Weight loss was observed in tree shrews but not ferrets. V0215 and Y12 replicated in all three animal (ferrets, tree shrews and mice) models with peak titers evident on 2DPI. There were no significant differences in peak viral titers in ferrets and tree shrews inoculated with Y12 at 2 and 4DPI, but viral titers were detected at 6DPI in tree shrews. Tree shrews infected with influenza B virus showed similar seroconversion and respiratory tract pathology to ferrets. Elevated levels of cytokines were detected in the tissues isolated from the respiratory tract after infection with either V0215 or Y12 compared to the levels in the uninfected control in both animals. Overall, the tree shrew was sensitive to infection and disease by influenza B virus.

Conclusion

The tree shrew to be a promising model for influenza B virus research.

SUBMITTER: Yuan B

PROVIDER: S-EPMC6555921 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundThe influenza pandemics have resulted in significant morbidity and mortality worldwide. Animal models are useful in the study of influenza virus pathogenesis. Because of various limitations in current laboratory animal models, it is essential to develop new alternative animal models for influenza virus research aimed at understanding the viral and host factors that contribute to virus infection in human.MethodWe investigated the replicative efficiency of influenza H1N1 virus (classic strain (Influenza A/PR/8/34), seasonal influenza isolate (A/Guangzhou/GIRD/02/09) and swine-origin human influenza virus (A/Guangzhou/GIRD/07/09)) at Day1,2,4,6 and 9 p.i. using TCID50 and qPCR assay in tree shrew model. Body temperature was monitored in the morning and evening for 3 days before infection and for 14 days. Seroconversion was detected by determining the neutralizing antibody titers against the challenge viruses in the pre- and exposure serum samples collected before infection and at 14 days p.i., respectively. Lungs and tracheas of tree shews were collected at day 14 post p.i. for histopathological analysis. Lectinhistochemistry analysis was conducted to identify the distribution of SAα2,3 Gal and SAα2,6 Gal receptors in the lung and trachea.ResultsThe infected tree shrew displayed mild or moderate systemic and respiratory symptoms and pathological changes in respiratory tracts. The human H1N1 influenza virus may replicate in the upper respiratory tract of tree shrews. Analysis of the receptors distribution in the respiratory tract of tree shrews by lectinhistochemistry showed that sialic acid (SA)α2,6-Gal receptors were widely distributed in the trachea and nasal mucosa, whereas (SA)α2,3-Gal receptor was the main receptor in the lung tissue.ConclusionsBased on these findings, tree shrew seemed to mimic well influenza virus infection in humans. We propose that tree shrews could be a useful alternative mammalian model to study pathogenesis of influenza H1N1 virus.

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