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The mouse and ferret models for studying the novel avian-origin human influenza A (H7N9) virus.

Xu L, Bao L, Deng W, Zhu H, Chen T, Lv Q, Li F, Yuan J, Xiang Z, Gao K, Xu Y, Huang L, Li Y, Liu J, Yao Y, Yu P, Yong W, Wei Q, Zhang L, Qin C - Virol. J. (2013)

Bottom Line: Virus could also be detected in brain, liver, spleen, kidney, and intestine from inoculated mice, and in heart, liver, and olfactory bulb from inoculated ferrets.Leukopenia, significantly reduced lymphocytes but increased neutrophils were also observed in mouse and ferret models.The mouse and ferret model enables detailed studies of the pathogenesis of this illness and lay the foundation for drug or vaccine evaluation.

View Article: PubMed Central - HTML - PubMed

Affiliation: Institute of Laboratory Animal Sciences, Chinese Academy of Medical Sciences (CAMS) & Comptive Medicine Center, Peking Union Medical Collage (PUMC), Key Laboratory of Human Disease Comptive Medicine, Ministry of Health, Beijing, China.

ABSTRACT

Background: The current study was conducted to establish animal models (including mouse and ferret) for the novel avian-origin H7N9 influenza virus.

Findings: A/Anhui/1/2013 (H7N9) virus was administered by intranasal instillation to groups of mice and ferrets, and animals developed typical clinical signs including body weight loss (mice and ferrets), ruffled fur (mice), sneezing (ferrets), and death (mice). Peak virus shedding from respiratory tract was observed on 2 days post inoculation (d.p.i.) for mice and 3-5 d.p.i. for ferrets. Virus could also be detected in brain, liver, spleen, kidney, and intestine from inoculated mice, and in heart, liver, and olfactory bulb from inoculated ferrets. The inoculation of H7N9 could elicit seroconversion titers up to 1280 in ferrets and 160 in mice. Leukopenia, significantly reduced lymphocytes but increased neutrophils were also observed in mouse and ferret models.

Conclusions: The mouse and ferret model enables detailed studies of the pathogenesis of this illness and lay the foundation for drug or vaccine evaluation.

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Clinical signs and gross examination of lung tissues of inoculated BALB/c mice or ferrets with H7N9 virus. (A) Clinical signs (i) and gross examination of the lungs (ii) of inoculated mice. (B) Clinical signs (i &ii), gross examination of the lungs (iii) of inoculated ferrets. (C) Micro-CT scanning of lungs of inoculated ferrets, the lesions were marked by ovals and arrows.
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Figure 2: Clinical signs and gross examination of lung tissues of inoculated BALB/c mice or ferrets with H7N9 virus. (A) Clinical signs (i) and gross examination of the lungs (ii) of inoculated mice. (B) Clinical signs (i &ii), gross examination of the lungs (iii) of inoculated ferrets. (C) Micro-CT scanning of lungs of inoculated ferrets, the lesions were marked by ovals and arrows.

Mentions: Mice do not run fevers or develop easy-to-measure respiratory clinical signs post inoculated with influenza viruses, however, mice display numerous physical signs of illness (including mortality, weight loss, ruffled fur, and lethargy) that can be used as indicator of pathogenicity. Female 6-week-old specific pathogen-free BALB/c mice used in this study were obtained from the Institute of Laboratory Animal Sciences, Beijing, China. Mice were anesthetized and inoculated intranasally with 50 μl of A/Anhui/1/2013 (H7N9) virus. Three groups of ten mice were septely inoculated with 108, 107, or 106 50% tissue culture infectious dose (TCID50) of H7N9 virus, and were observed daily for signs of disease and mortality up to 14 days. The percentages of mice that survived during the observation period were shown in Figure 1A. All of the mice inoculated with 106 TCID50 of virus survived. In contrast, only 80% and 40% of the mice inoculated with 107 or 108 TCID50 of virus survived on 14 d.p.i. For mice inoculated with 106 TCID50 of virus, the loss of body weight was observed from 2 d.p.i. and the peak loss reached 28.9% on 9 d.p.i., after which the mice began to steadily regain their body weight over the remaining observation period (Figure 1B and Table 1). Meanwhile, ruffled fur appeared from 3 d.p.i. and the occurrence rate reached 100% from 4 d.p.i. until 14 d.p.i.(Figure 2A (i) and Table 1). Furthermore, thirty mice were also inoculated with 106 TCID50 of H7N9 virus, and six were selected randomly and euthanized on 1, 2, 3, 5, 7 d.p.i. respectively for virus dissemination and pathology analysis. From 3 to 7 d.p.i., gross examination of the lungs revealed focal to multifocal consolidation in all inoculated mice (Figure 2A (ii)). However, gross examination of the heart, liver, spleen, kidney and brain did not reveal lesions in inoculated mice.


The mouse and ferret models for studying the novel avian-origin human influenza A (H7N9) virus.

Xu L, Bao L, Deng W, Zhu H, Chen T, Lv Q, Li F, Yuan J, Xiang Z, Gao K, Xu Y, Huang L, Li Y, Liu J, Yao Y, Yu P, Yong W, Wei Q, Zhang L, Qin C - Virol. J. (2013)

Clinical signs and gross examination of lung tissues of inoculated BALB/c mice or ferrets with H7N9 virus. (A) Clinical signs (i) and gross examination of the lungs (ii) of inoculated mice. (B) Clinical signs (i &ii), gross examination of the lungs (iii) of inoculated ferrets. (C) Micro-CT scanning of lungs of inoculated ferrets, the lesions were marked by ovals and arrows.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3750532&req=5

Figure 2: Clinical signs and gross examination of lung tissues of inoculated BALB/c mice or ferrets with H7N9 virus. (A) Clinical signs (i) and gross examination of the lungs (ii) of inoculated mice. (B) Clinical signs (i &ii), gross examination of the lungs (iii) of inoculated ferrets. (C) Micro-CT scanning of lungs of inoculated ferrets, the lesions were marked by ovals and arrows.
Mentions: Mice do not run fevers or develop easy-to-measure respiratory clinical signs post inoculated with influenza viruses, however, mice display numerous physical signs of illness (including mortality, weight loss, ruffled fur, and lethargy) that can be used as indicator of pathogenicity. Female 6-week-old specific pathogen-free BALB/c mice used in this study were obtained from the Institute of Laboratory Animal Sciences, Beijing, China. Mice were anesthetized and inoculated intranasally with 50 μl of A/Anhui/1/2013 (H7N9) virus. Three groups of ten mice were septely inoculated with 108, 107, or 106 50% tissue culture infectious dose (TCID50) of H7N9 virus, and were observed daily for signs of disease and mortality up to 14 days. The percentages of mice that survived during the observation period were shown in Figure 1A. All of the mice inoculated with 106 TCID50 of virus survived. In contrast, only 80% and 40% of the mice inoculated with 107 or 108 TCID50 of virus survived on 14 d.p.i. For mice inoculated with 106 TCID50 of virus, the loss of body weight was observed from 2 d.p.i. and the peak loss reached 28.9% on 9 d.p.i., after which the mice began to steadily regain their body weight over the remaining observation period (Figure 1B and Table 1). Meanwhile, ruffled fur appeared from 3 d.p.i. and the occurrence rate reached 100% from 4 d.p.i. until 14 d.p.i.(Figure 2A (i) and Table 1). Furthermore, thirty mice were also inoculated with 106 TCID50 of H7N9 virus, and six were selected randomly and euthanized on 1, 2, 3, 5, 7 d.p.i. respectively for virus dissemination and pathology analysis. From 3 to 7 d.p.i., gross examination of the lungs revealed focal to multifocal consolidation in all inoculated mice (Figure 2A (ii)). However, gross examination of the heart, liver, spleen, kidney and brain did not reveal lesions in inoculated mice.

Bottom Line: Virus could also be detected in brain, liver, spleen, kidney, and intestine from inoculated mice, and in heart, liver, and olfactory bulb from inoculated ferrets.Leukopenia, significantly reduced lymphocytes but increased neutrophils were also observed in mouse and ferret models.The mouse and ferret model enables detailed studies of the pathogenesis of this illness and lay the foundation for drug or vaccine evaluation.

View Article: PubMed Central - HTML - PubMed

Affiliation: Institute of Laboratory Animal Sciences, Chinese Academy of Medical Sciences (CAMS) & Comptive Medicine Center, Peking Union Medical Collage (PUMC), Key Laboratory of Human Disease Comptive Medicine, Ministry of Health, Beijing, China.

ABSTRACT

Background: The current study was conducted to establish animal models (including mouse and ferret) for the novel avian-origin H7N9 influenza virus.

Findings: A/Anhui/1/2013 (H7N9) virus was administered by intranasal instillation to groups of mice and ferrets, and animals developed typical clinical signs including body weight loss (mice and ferrets), ruffled fur (mice), sneezing (ferrets), and death (mice). Peak virus shedding from respiratory tract was observed on 2 days post inoculation (d.p.i.) for mice and 3-5 d.p.i. for ferrets. Virus could also be detected in brain, liver, spleen, kidney, and intestine from inoculated mice, and in heart, liver, and olfactory bulb from inoculated ferrets. The inoculation of H7N9 could elicit seroconversion titers up to 1280 in ferrets and 160 in mice. Leukopenia, significantly reduced lymphocytes but increased neutrophils were also observed in mouse and ferret models.

Conclusions: The mouse and ferret model enables detailed studies of the pathogenesis of this illness and lay the foundation for drug or vaccine evaluation.

Show MeSH
Related in: MedlinePlus