Mice as Small Animal Model for <i>Human Norovirus</i> Infection


  • Warda E. Rusdi Doctoral Program of Medical Science, Faculty of Medicine, Universitas Airlangga, Surabaya, Indonesia
  • Soetjipto Department of Medical Biochemistry, Faculty of Medicine, Universitas Airlangga, Surabaya, Indonesia
  • Marie I. Lusida Department of Microbiology, Faculty of Medicine, Universitas Airlangga, Surabaya, Indonesia
  • Zayyin Dinana Institute of Tropical Disease, Universitas Airlangga, Surabaya, Indonesia
  • Aussie T. Maharani Institute of Tropical Disease, Universitas Airlangga, Surabaya, Indonesia
  • Irmawan Farindra Department of Anatomy and Histology, Faculty of Medicine, Universitas Nahdlatul Ulama Surabaya, Surabaya, Indonesia
  • Nailul Huda Faculty of Medicine, Universitas Nahdlatul Ulama Surabaya, Surabaya, Indonesia
  • Radia R. Maharani Faculty of Medicine, Universitas Nahdlatul Ulama Surabaya, Surabaya, Indonesia
  • Ayu A. A. Hamida Faculty of Medicine, Universitas Nahdlatul Ulama Surabaya, Surabaya, Indonesia




Diarrhea, Mice, Animal Model, Norovirus


Despite being discovered in 1972, the development of vaccines to prevent Human Norovirus (HuNoV) infection in humans remains limited. This limitation is partly due to inadequate knowledge about Norovirus infection in non-human hosts and its pathogenic process. This research was performed to assess the efficacy of HuNoV infection in mice as an animal model by using both different infection routes and virus titers. In this research, 20 BALB/c Mus musculus were used as the test animals which were randomly divided into 4 groups. Intraperitoneal and oral infection methods were employed using different viral titers. The mice were euthanized on the fifth day to obtain fecal samples from the colon organ. Afterwards, Quantitative Polymerase Chain Reaction (qPCR) was administered to evaluate these samples. Most of the mice did not show symptom, except one mouse that experienced diarrhea. The HuNoV virus replication in the mice was measured using qPCR analysis. Three of the twenty mice showed elevated virus titers after being infected with HuNoV. In conclusion, BALB/c strain mice remained resistant to HuNoV infection when exposed to the virus through the oral route. Conversely, the use of high viral titers for intraperitoneal infection indicated the presence of viral replication.

Author Biography

Warda E. Rusdi, Doctoral Program of Medical Science, Faculty of Medicine, Universitas Airlangga, Surabaya, Indonesia

Department of Public Health, Faculty of Medicine, Universitas Nahdlatul Ulama Surabaya, Surabaya, Indonesia


Utsumi T, Lusida MI, Dinana Z, Wahyuni RM, Soegijanto S, Soetjipto, Athiyyah AF, Sudarmo SM, Ranuh RG, Darma A, Juniastuti, Yamani LN, Doan YH, Shimizu H, Ishii K, Matsui C, Deng L, Abe T, Katayama K, Shoji I. Molecular epidemiology and genetic diversity of norovirus infection in children hospitalized with acute gastroenteritis in East Java, Indonesia in 2015–2019. Infection, Genetics and Evolution. 2021; 1;88.

Khamrin P, Kumthip K, Yodmeeklin A, Supadej K, Ukarapol N, Thongprachum A, Okitsu S, Hayakawa S, Ushijima H, Maneekarn N. Molecular characterization of norovirus GII.17 detected in healthy adult, intussusception patient, and acute gastroenteritis children in Thailand. Infection, Genetics and Evolution. 2016; 44:330–3.

Ahmed SM, Hall AJ, Robinson AE, Verhoef L, Premkumar P, Parashar UD, Koopmans M, Lopman BA. Global prevalence of norovirus in cases of gastroenteritis: a systematic review and meta-analysis. Lancet Infect Dis [Internet]. 2014 [cited 2023 Jul 26];14(8):725–30. Available from: https://pubmed.ncbi.nlm.nih.gov/24981041/

Hikal WM, Ahl HAHSA, Tkachenko KG, Mahmoud AA, Bratovcic A, Hodžić S, Atanassova M. An Overview of Pomegranate Peel: A Waste Treasure for Antiviral Activity. Trop J Nat Prod Res. 2022 Feb 3;6(1):15–9.

Lopman B, Armstrong B, Atchison C, Gray JJ. Host, weather and virological factors drive norovirus epidemiology: Time-series analysis of laboratory surveillance data in England and Wales. PLoS One. 2009;4(8): e6671

Matthews JE, Dickey BW, Miller RD, Felzer JR, Dawson BP, Lee AS, Rocks JJ, Kiel J, Montes JS, Moe CL, Eisenberg JN< Leon JS. The Epidemiology of Published Norovirus Outbreaks: A Systematic Review of Risk Factors Associated with Attack Rate and Genogrup. Epidemiol Infect. 2012;140(7):1161–72.

Marshall JA, Bruggink LD. The dynamics of norovirus outbreak epidemics: recent insights. Int J Environ Res Public Health. 2011;8(4):1141–9.

Green KY. Caliciviridae: The Noroviruses. In: Knipe DM, Howley PM, Griffin DE, Greenberg HB, Wyatt RG, editors. Fields Virolgy. 6th ed. Philadelphia: Lippincot Williams & Wilkins; 2007. p. 594.

Green J, Vinje J, Gallimore CI, Koopmans M, Hale A, Brown DW, Clegg JC, Chamberlain J. Capsid Protein Diversity among Norway-like Viruses. Virus Genes. 2000;20(3):227–36.

Wobus CE, Cunha JB, Elftman MD, Kolawole AO. Animal Models of Norovirus Infection. In: Viral Gastroenteritis. Elsevier; 2016. p. 397–422.

Souza M, Azevedo MSP, Jung K, Cheetham S, Saif LJ. Pathogenesis and Immune Responses in Gnotobiotic Calves after Infection with the Genogroup II.4-HS66 Strain of Human Norovirus. J Virol. 2008; 15;82(4):1777–86.

Lou F, Ye M, Ma Y, Li X, DiCaprio E, Chen H, Krakowka S, Hughes J, Kingsley D, Li. A Gnotobiotic Pig Model for Determining Human Norovirus Inactivation by High-Pressure Processing. Appl Environ Microbiol. 2015; 81(19):6679–87.

Souza M, Cheetham SM, Azevedo MSP, Costantini V, Saif LJ. Cytokine and Antibody Responses in Gnotobiotic Pigs after Infection with Human Norovirus Genogroup II.4 (HS66 Strain). J Virol. 2007; 81(17):9183–92.

Takanashi S, Wang Q, Chen N, Shen Q, Jung K, Zhang Z, Yokoyama M, Lindesmith LC, Baric RS, Saif LJ. Characterization of Emerging GII.g/GII.12 Noroviruses from a Gastroenteritis Outbreak in the United States in 2010. J Clin Microbiol. 2011 Sep;49(9):3234–44.

Lei S, Samuel H, Twitchell E, Bui T, Ramesh A, Wen K, Weiss M, Li G, Yang X, Jiang X, Yuan L. Enterobacter cloacae inhibits human norovirus infectivity in gnotobiotic pigs. Sci Rep. 2016 Apr 26;6(1):25017.

Kocher J, Bui T, Giri-Rachman E, Wen K, Li G, Yang X, Liu F, Tan M, Xia M, Zhong W, Jiang Y, Yuan L. Intranasal P Particle Vaccine Provided Partial Cross-Variant Protection against Human GII.4 Norovirus Diarrhea in Gnotobiotic Pigs. J Virol. 2014 Sep;88(17):9728–43.

Cheetham S, Souza M, Meulia T, Grimes S, Han MG, Saif LJ. Pathogenesis of a Genogroup II Human Norovirus in Gnotobiotic Pigs. J Virol. 2006 Nov;80(21):10372–81.

Park BJ, Jung ST, Choi C, Myoung J, Ahn HS, Han SH, Kim YH, Go HJ, Lee JB, Park SY, Song CS, Lee SW, Choi IS. Pathogenesis of Human Norovirus Genogroup II Genotype 4 in Post-Weaning Gnotobiotic Pigs. J Microbiol Biotechnol [Internet]. 2018 Dec 28 [cited 2023 Oct 3];28(12):2133–40. Available from: https://pubmed.ncbi.nlm.nih.gov/30661347/

He Z, Liu B, Tao Y, Li C, Xia M, Zhong W, Jiang X, Liu H, Tan M. Norovirus GII.17 natural infections in Rhesus monkeys, China. Emerg Infect Dis. 2017 Feb 1;23(2):316–9.

Sestak K, Feely S, Fey B, Dufour J, Hargitt E, Alvarez X, Pahar B, Gregoricus N, Vinjé J, Farkas T. Experimental Inoculation of Juvenile Rhesus Macaques with Primate Enteric Caliciviruses. PLoS One. 2012 May 30;7(5):e37973.

Rockx BHG, Bogers WMJM, Heeney JL, van Amerongen G, Koopmans MPG. Experimental norovirus infections in non-human primates. J Med Virol. 2005 Feb;75(2):313–20.

Bok K, Parra GI, Mitra T, Abente E, Shaver CK, Boon D, Engle R, Yu C, Kapikian AZ, Sosnovtsev SV, Purcell RH, Green KY. Chimpanzees as an animal model for human norovirus infection and vaccine development. Proceedings of the National Academy of Sciences. 2011 Jan 4;108(1):325–30.

Wulandari PS, Juniastuti, Wahyuni RM, Amin M, Yamani LN, Matondang MQY, Dinana Z, Soetjipto, Utsumi T, Shoji I, Lusida MI. Predominance of norovirus GI.4 from children with acute gastroenteritis in Jambi, Indonesia, 2019. J Med Virol [Internet]. 2020 Dec 1 [cited 2024 Apr 2];92(12):3165–72. Available from: https://pubmed.ncbi.nlm.nih.gov/32445492/

Thangjui S, Sripirom N, Titichoatrattana S, Mekmullica J. Accuracy and Cross-Reactivity of Rapid Diagnostic Tests for Norovirus and Rotavirus in a Real Clinical Setting. Infect Chemother. 2020;52(3):360.

Subekti DS, Tjaniadi P, Lesmana M, McArdle J, Iskandriati D, Budiarsa IN, Walujo P, Suparto IH, Winoto I, Campbell JR, Porter KR, Sajuthi D, Ansari AA, Oyofo BA. Experimental infection ofMacaca nemestrina with a Toronto Norwalk-like virus of epidemic viral gastroenteritis. J Med Virol. 2002 Mar;66(3):400–6.

Taube S, Kolawole AO, Höhne M, Wilkinson JE, Handley SA, Perry JW, Thackray LB, Akkina R, Wobus CE. A Mouse Model for Human Norovirus. mBio. 2013 30;4(4).

Lucero Y, Lagomarcino AJ, Espinoza M, Kawakami N, Mamani N, Huerta N, Del Canto F, Farfán M, Sawaguchi Y, George S, O’Ryan M. Norovirus compared to other relevant etiologies of acute gastroenteritis among families from a semirural county in Chile. International Journal of Infectious Diseases. 2020;101:353–60.

Bryda EC. The Mighty Mouse: The Impact of Rodents on Advances in Biomedical Research. Mo Med [Internet]. 2013 [cited 2024 Mar 14];110(3):207. Available from: /pmc/articles/PMC3987984/




How to Cite

Rusdi, W. E., Soetjipto, Lusida, M. I., Dinana, Z., Maharani, A. T., Farindra, I., … Hamida, A. A. A. (2024). Mice as Small Animal Model for <i>Human Norovirus</i> Infection. Tropical Journal of Natural Product Research (TJNPR), 8(5), 7089–7092. https://doi.org/10.26538/tjnpr/v8i5.6