Freitas Natalia, Lukash Tetyana, Dudek Megan, Litwin Sam, Menne Stephan, Gudima Severin O
Department of Microbiology, Molecular Genetics and Immunology, University of Kansas Medical Center, 3901 Rainbow Boulevard, Kansas City, KS 66160, USA.
Biostatistics and Bioinformatics Facility, Fox Chase Cancer Center, 333 Cottman Avenue, Philadelphia, PA 19111, USA.
Virus Res. 2015 Jul 2;205:12-21. doi: 10.1016/j.virusres.2015.05.003. Epub 2015 May 12.
Woodchuck hepatitis virus (WHV) is often used as surrogate to study mechanism of HBV infection. Currently, most infections are conducted using strains WHV7 or WHV8 that have very high sequence identity. This study focused on natural strain WHVNY that is more genetically distant from WHV7. Three naive adult woodchucks inoculated with WHVNY developed productive acute infection with long lasting viremia. However, only one of two woodchucks infected with WHV7 at the same multiplicity demonstrated productive liver infection. Quantification of intracellular WHV RNA and DNA replication intermediates; percentages of core antigen-positive hepatocytes; and serum relaxed circular DNA showed that strains WHVNY and WHV7 displayed comparable replication levels and capacities to induce acute infection in naive adult woodchucks. Strain WHVNY was therefore validated as valuable reagent to analyze the mechanism of hepadnavirus infection, especially in co- and super-infection settings, which required discrimination between two related virus genomes replicating in the same liver.
土拨鼠肝炎病毒（WHV）常被用作研究乙肝病毒（HBV）感染机制的替代物。目前，大多数感染实验使用的是序列同一性非常高的WHV7或WHV8毒株。本研究聚焦于与WHV7在基因上距离更远的天然毒株WHVNY。三只接种了WHVNY的未感染成年土拨鼠发生了有病毒血症的持续性急性感染。然而，以相同感染复数感染WHV7的两只土拨鼠中，只有一只出现了肝脏感染。对细胞内WHV RNA和DNA复制中间体的定量分析；核心抗原阳性肝细胞的百分比；以及血清松弛环状DNA结果显示，WHVNY和WHV7毒株在未感染成年土拨鼠中诱导急性感染时，表现出相当的复制水平和能力。因此，WHVNY毒株被确认为是分析嗜肝DNA病毒感染机制的有价值试剂，尤其适用于共感染和重叠感染情况，这需要区分在同一肝脏中复制的两个相关病毒基因组。
