DBA/2 mouse as an animal model for anti-influenza drug efficacy evaluation

Kim, Sang Hyun; Park, Sehee; Lee, Sang Moo; Lee, Ilseob; Heo, Jun; Hwang, Miriam; Bae, Jin‐Young; Kim, Dong Hwan; Jang, Seok Il; Park, Mee Sook; Park, Man Seong

doi:10.1007/s12275-013-3428-7

Cited by 15 publications

(9 citation statements)

References 43 publications

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“…This observation has also been made by others (Dengler et al, 2012; Pica et al, 2011). DBA.2 mice offer the additional advantage of being susceptible to influenza viruses that have not been mouse-adapted (Boon et al, 2010; Kim et al, 2013). Therefore, several investigators have proposed the use of DBA.2 mice as a suitable small animal model to study influenza virus pathogenicity and for the evaluation of anti-influenza drug efficacies.…”

Section: Discussionmentioning

confidence: 99%

Serum amyloid A (SAA) is an early biomarker of influenza virus disease in BALB/c, C57BL/2, Swiss-Webster, and DBA.2 mice

2016

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Assessment of influenza virus disease progression and efficacy of antiviral therapy in the widely used mouse models relies mostly on body weight loss and lung virus titers as markers of disease. However, both parameters have their shortcomings. Therefore, the aim of our study was to find non-invasive markers in the murine model of severe influenza that could detect disease early and predict disease outcome. BALB/c mice were lethally infected with influenza A(H1N1)pdm09 virus and serum samples were collected at various time points. Enzyme-linked immunosorbent assays were performed to quantify amounts of serum amyloid A (SAA), C-reactive protein, complement 3, transferrin, corticosterone, prostaglandin E2, H2O2, and alpha-2,6-sialyltransferase. We found that SAA was the most promising candidate with levels acutely and temporarily elevated by several hundred-fold 3 days post virus inoculation. Upon treatment with oseltamivir phosphate, levels of SAA were significantly decreased. High levels of SAA were associated with poor disease prognosis, whereas body weight loss was not as a reliable predictor of disease outcome. SAA levels were also transiently increased in BALB/c mice infected with influenza A(H3N2) and influenza B virus, as well as in C57BL/2, Swiss-Webster, and DBA.2 mice infected with influenza A(H1N1)pdm09 virus. High levels of SAA often, but not always, were associated with disease outcome in these other influenza virus mouse models. Therefore, SAA represents a valid biomarker for influenza disease detection in all tested mouse strains but its prognostic value is limited to BALB/c mice infected with influenza A(H1N1)pdm09 virus.

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Section: Discussionmentioning

confidence: 99%

Serum amyloid A (SAA) is an early biomarker of influenza virus disease in BALB/c, C57BL/2, Swiss-Webster, and DBA.2 mice

2016

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“…In the present study, we investigated the combination efficacy of peramivir and favipiravir against oseltamivir-resistant 2009 pandemic H1N1 virus infection in a DBA/2 mouse model, which was recently validated for the influenza antiviral screening study [31]. To compare with monotherapy, the mice were treated with the various combination sets of chemotherapy.…”

Section: Introductionmentioning

confidence: 99%

Combination Effects of Peramivir and Favipiravir against Oseltamivir-Resistant 2009 Pandemic Influenza A(H1N1) Infection in Mice

et al. 2014

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Antiviral drugs are being used for therapeutic purposes against influenza illness in humans. However, antiviral-resistant variants often nullify the effectiveness of antivirals. Combined medications, as seen in the treatment of cancers and other infectious diseases, have been suggested as an option for the control of antiviral-resistant influenza viruses. Here, we evaluated the therapeutic value of combination therapy against oseltamivir-resistant 2009 pandemic influenza H1N1 virus infection in DBA/2 mice. Mice were treated for five days with favipiravir and peramivir starting 4 hours after lethal challenge. Compared with either monotherapy, combination therapy saved more mice from viral lethality and resulted in increased antiviral efficacy in the lungs of infected mice. Furthermore, the synergism between the two antivirals, which was consistent with the survival outcomes of combination therapy, indicated that favipiravir could serve as a critical agent of combination therapy for the control of oseltamivir-resistant strains. Our results provide new insight into the feasibility of favipiravir in combination therapy against oseltamivir-resistant influenza virus infection.

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“…Additionally, the DBA mouse has been found to have much higher susceptibility to influenza infection than either C56BL/6 or BALB/c mice (5,6). A variety of influenza viruses, including H5N1 and influenza B viruses, have been shown to be lethal to DBA mice without prior adaptation (7,8).…”

mentioning

confidence: 99%

A broadly neutralizing human monoclonal antibody is effective against H7N9

Tharakaraman

Subramanian

Viswanathan

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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Emerging strains of influenza represent a significant public health threat with potential pandemic consequences. Of particular concern are the recently emerged H7N9 strains which cause pneumonia with acute respiratory distress syndrome. Estimates are that nearly 80% of hospitalized patients with H7N9 have received intensive care unit support. VIS410, a human antibody, targets a unique conserved epitope on influenza A. We evaluated the efficacy of VIS410 for neutralization of group 2 influenza strains, including H3N2 and H7N9 strains in vitro and in vivo. VIS410, administered at 50 mg/kg, protected DBA mice infected with A/Anhui/2013 (H7N9), resulting in significant survival benefit upon single-dose (−24 h) or double-dose (−12 h, +48 h) administration (P < 0.001). A single dose of VIS410 at 50 mg/kg (−12 h) combined with oseltamivir at 50 mg/kg (−12 h, twice daily for 7 d) in C57BL/6 mice infected with A/Shanghai 2/2013 (H7N9) resulted in significant decreased lung viral load (P = 0.002) and decreased lung cytokine responses for nine of the 11 cytokines measured. Based on these results, we find that VIS410 may be effective either as monotherapy or combined with antivirals in treating H7N9 disease, as well as disease from other influenza strains.

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DBA/2 mouse as an animal model for anti-influenza drug efficacy evaluation

Cited by 15 publications

References 43 publications

Serum amyloid A (SAA) is an early biomarker of influenza virus disease in BALB/c, C57BL/2, Swiss-Webster, and DBA.2 mice

Serum amyloid A (SAA) is an early biomarker of influenza virus disease in BALB/c, C57BL/2, Swiss-Webster, and DBA.2 mice

Combination Effects of Peramivir and Favipiravir against Oseltamivir-Resistant 2009 Pandemic Influenza A(H1N1) Infection in Mice

A broadly neutralizing human monoclonal antibody is effective against H7N9

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