Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2020 May 29;12(6):590.
doi: 10.3390/v12060590.

Non-Mouse-Adapted H1N1pdm09 Virus as a Model for Influenza Research

Irina Kiseleva  1 , Andrey Rekstin  1 , Mohammad Al Farroukh  1 , Ekaterina Bazhenova  1 , Anastasia Katelnikova  2 , Ludmila Puchkova  1 , Larisa Rudenko  1
Affiliations

Non-Mouse-Adapted H1N1pdm09 Virus as a Model for Influenza Research

Irina Kiseleva et al. Viruses. .

Abstract

The number of lung-adapted influenza viruses is limited. Most of them are not antigenically related to current circulating viruses. Viruses similar to recent strains are required for screening modern antiviral compounds and studying new vaccine candidates against novel influenza viruses. The process by which an influenza virus adapts to a new host is rather difficult. The aim of this study was to select a non-adapted current virus whose major biological properties correspond to those of classical lab-adapted viruses. Mice were inoculated intranasally with non-lung-adapted influenza viruses of subtype H1N1pdm09. They were monitored closely for body weight loss, mortality outcomes and gross pathology for 14 days following inoculation, as well as viral replication in lung tissue. Lung-adapted PR8 virus was used as a control. The tested viruses multiplied equally well in the lower respiratory tract of mice without prior adaptation but dramatically differed in lethality; the differences in their toxicity and pathogenicity in mice were established. A/South Africa/3626/2013 (H1N1)pdm09 virus was found to be an appropriate candidate to replace PR8 as a model virus for influenza research. No prior adaptation to the animal model is needed to reach the pathogenicity level of the classical mouse-adapted PR8 virus.

Keywords: animal model; influenza infection; influenza virus; viral pathogenesis; viral toxicity.

PubMed Disclaimer

Conflict of interest statement

The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.

Figures

Figure 1
Figure 1
Weight loss and lethality of the influenza viruses for BALB/c mice. Weight loss, %, p < 0.05 (a,c,e), and survival, % (b,d,f), were monitored daily for 14 days. Mice were inoculated intranasally with 8.5 log10 EID50 (a,b), 7.5 log10 EID50 (c,d) or 5.0 log10 EID50 (1–10 LD50) (e,f).
Figure 2
Figure 2
Gross examination of the lungs of mice infected with A/South Africa/3626/2013 (H1N1)pdm09 influenza virus: (a) hemorrhagic pulmonary edema (8.2 log10 EID50/mouse, D4); (b) primary viral pneumonia (1 PnD50/mouse = 5.0 log10 EID50/mouse, D14); (c) normal lungs of a control mouse inoculated with phosphate-buffered saline (PBS) (D14).
Figure 3
Figure 3
Lethality of the influenza viruses for the BALB/c mice. The mice were inoculated with a massive dose of influenza virus (8.0–9.0 log10 EID50/mL).
Figure 4
Figure 4
Nasal symptoms and gross examination of the lungs of the ferrets infected with A/South Africa/3626/2013 (H1N1)pdm09 influenza virus. (a,b) The ferrets were inoculated with 6.0 log10 EID50. (a) Severe lung lesions were registered on day 4 post infection. (b) On D3 post infection, the animals displayed sneezing, nasal discharge on the external nares (red arrow) and mouth breathing. (c) In contrast, the lungs of the ferrets inoculated with PBS were normal.
Figure 5
Figure 5
Virus replication in the lungs and upper respiratory tract of the ferrets as measured by titration in embryonated chicken eggs (mean ± SD).
Figure 6
Figure 6
Body temperature of the ferrets after infection with the SA influenza virus: (a) variation in the body temperature until 4 days post infection (raw data). The temporary decreases in temperature were the result of sedation during the collection of nasal washes. The body temperature was recorded by temperature loggers every 10 min; (b) the difference between the infected group and the control group, represented by the mean ± SD, p < 0.05.
Figure 7
Figure 7
Phylogenetic trees of hemagglutinin (upper panel) and neuraminidase (lower panel) of the H1N1pdm09 influenza viruses. The website https://nextstrain.org/ [21] was used to construct the figure. Black cross: A/California/07/2009; black circle: A/South Africa/3626/2013.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Barnard D.L. Animal models for the study of influenza pathogenesis and therapy. Antivir. Res. 2009;82:A110–A122. doi: 10.1016/j.antiviral.2008.12.014. - DOI - PMC - PubMed
    1. Bouvier N.M., Lowen A.C. Animal Models for Influenza Virus Pathogenesis and Transmission. Viruses. 2010;2:1530–1563. doi: 10.3390/v20801530. - DOI - PMC - PubMed
    1. Enkirch T., von Messling V. Ferret models of viral pathogenesis. Virology. 2015;479–480:259–270. doi: 10.1016/j.virol.2015.03.017. - DOI - PMC - PubMed
    1. Matsuoka Y., Lamirande E.W., Subbarao K. The mouse model for influenza. Curr. Protoc. Microbiol. 2009;15:15G3.1–15G.3.30. doi: 10.1002/9780471729259.mc15g03s13. - DOI - PubMed
    1. Thangavel R.R., Bouvier N.M. Animal models for influenza virus pathogenesis, transmission, and immunology. J. Immunol. Methods. 2014;410:60–79. doi: 10.1016/j.jim.2014.03.023. - DOI - PMC - PubMed

Publication types

LinkOut - more resources