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.
The study was supported by the National Natural Science Foundation of China (Grant No. 81702007 and 81290345).
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.
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