Experimental infection of Marmota monax with a novel hepatitis A virus
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To establish an animal model for the newly identified Marmota Himalayana hepatovirus, MHHAV, so as to develop a better understanding of the infection of hepatitis A viruses. Five experimental woodchucks (Marmota monax) were inoculated intravenously with the purified MHHAV from wild woodchuck feces. One animal injected with PBS was defined as a control. Feces and blood were routinely collected. After the animals were subjected to necropsy, different tissues were collected. The presence of viral RNA and negative sense viral RNA was analyzed in all the samples and histopathological and in situ hybridization analysis was performed for the tissues. MHHAV infection caused fever but no severe symptoms or death. Virus was shed in feces beginning at 2 dpi, and MHHAV RNA persisted in feces for ~2 months, with a biphasic increase, and in blood for ~30 days. Viral RNA was detected in all the tissues, with high levels in the liver and spleen. Negative-strand viral RNA was detected only in the liver. Furthermore, the animals showed histological signs of hepatitis at 45 dpi. MHHAV can infect M. monax and is associated with hepatic disease. Therefore, this animal can be used as a model of HAV pathogenesis and to evaluate antiviral and anticancer therapeutics.
Compliance with ethical standards
Conflict of interest
The authors declare that they have no competing interests.
Six healthy male woodchucks (M. monax) (age, 1–3 years; weight, 1.8–2.4 kg) were purchased from the Institute of Laboratory Animal Sciences, Chinese Academy of Medical Science and Peking Union Medical College.
All experiments involving MHHAV-infected animals were performed in biosafety level 2 containment at the Experimental Animal Center of the China CDC, in accordance with institutional guidelines. The animal study protocol was approved by the China CDC Animal Welfare Committee.
- 1.Amado LA, Marchevsky RS, de Paula VS, Hooper C, Freire Mda S, Gaspar AM, Pinto MA (2010) Experimental hepatitis A virus (HAV) infection in cynomolgus monkeys (Macaca fascicularis): evidence of active extrahepatic site of HAV replication. Int J Exp Pathol 91:87–97CrossRefPubMedPubMedCentralGoogle Scholar
- 2.Anthony SJ, St Leger JA, Liang E, Hicks AL, Sanchez-Leon MD, Jain K, Lefkowitch JH, Navarrete-Macias I, Knowles N, Goldstein T, Pugliares K, Ip HS, Rowles T, Lipkin WI (2015) Discovery of a novel hepatovirus (Phopivirus of Seals) related to human hepatitis A virus. MBio 6:e01180CrossRefPubMedPubMedCentralGoogle Scholar
- 8.Drexler JF, Corman VM, Lukashev AN, van den Brand JM, Gmyl AP, Brunink S, Rasche A, Seggewibeta N, Feng H, Leijten LM, Vallo P, Kuiken T, Dotzauer A, Ulrich RG, Lemon SM, Drosten C (2015) Evolutionary origins of hepatitis A virus in small mammals. Proc Natl Acad Sci USA 112:15190–15195CrossRefPubMedPubMedCentralGoogle Scholar
- 13.Hirai-Yuki A, Hensley L, McGivern DR, Gonzalez-Lopez O, Das A, Feng H, Sun L, Wilson JE, Hu F, Feng Z, Lovell W, Misumi I, Ting JP, Montgomery S, Cullen J, Whitmire JK, Lemon SM (2016) MAVS-dependent host species range and pathogenicity of human hepatitis A virus. Science 353:1541–1545CrossRefPubMedPubMedCentralGoogle Scholar
- 17.Lanford RE, Feng Z, Chavez D, Guerra B, Brasky KM, Zhou Y, Yamane D, Perelson AS, Walker CM, Lemon SM (2011) Acute hepatitis A virus infection is associated with a limited type I interferon response and persistence of intrahepatic viral RNA. Proc Natl Acad Sci USA 108:11223–11228CrossRefPubMedPubMedCentralGoogle Scholar
- 23.Munne MS, Canero Velasco MC, Moreiro R, Vladimirsky S, Otegui L, Castro R, Brajterman L, Soto S, Mutti J, Nucifora S, Lara E, Sosa A, Godoy P, Ciocca M, Cuarterolo M, Quarleri JF, Gonzalez JE (2006) Duration of viremia and fecal shedding of the virus in hepatitis A infected children. Acta Gastroenterol Latinoam 36:182–189PubMedGoogle Scholar
- 24.Pinto MA, Marchevsky RS, Baptista ML, de Lima MA, Pelajo-Machado M, Vitral CL, Kubelka CF, Pissurno JW, Franca MS, Schatzmayr HG, Gaspar AM (2002) Experimental hepatitis A virus (HAV) infection in Callithrix jacchus: early detection of HAV antigen and viral fate. Exp Toxicol Pathol 53:413–420CrossRefPubMedGoogle Scholar