MDPV和GPV在基因组水平上具有很高同源性，但在感染谱上却差异明显。MDPV仅感染雏番鸭而不感染雏鹅，GPV不仅感染雏鹅也能感染雏番鸭，而且对后者致病力还要强于MDPV，这一致病性差异的机理一直未予阐明。先前研究中，我们构建了GPV 强毒株LH的感染性质粒pLH，本研究中，拟进一步构建MDPV 强毒株NY的感染性质粒pNY。在对MDPV和GPV基因组序列比对基础上，拟在pNY和pLH质粒之间互换差异DNA片段，从而获得一系列嵌合对方DNA片段的重组质粒，通过绒毛尿囊膜途径转染番鸭胚或鹅胚来拯救嵌合病毒，并在雏番鸭或雏鹅上进行毒力试验来评估嵌合病毒的致病性，据此可以精确定位哪些DNA区域与MDPV和GPV的致病性差异相关联。在此基础上，拟对关键氨基酸或碱基予以定点突变并验证这些位点在致病性差异中的作用。阐明MDPV和GPV致病性差异的分子基础对深入揭示水禽细小病毒的致病机理将发挥指引作用。

Muscovy duck parvovirus (MDPV) and Goose parvovirus (GPV) are classified in the Dependovirus genus of the Parvoviridae family. Both viruses cause serious loss in geese and ducks industry. The goose parvoviral disease is often called “Derzsy’s disease” or “Gosling plaque” in China, and the muscovy parvoviral disease is also named “three-week disease”, which imply the infection often occur in 3-week-old muscovy ducklings. In case of B strain of GPV and FM strain of MDPV, they share 82% homologies at the genome level. Comparisons of the coding proteins between MDPV and GPV show that the Rep protein and the VP1 protein display 90.6% and 87.7% identities at the amino acid level, respectively. Irrespective of the high similarity between GPV and MDPV, two viruses have different host ranges. MDPV infects muscovy ducklings only, while GPV is infectious for both goslings and muscovy ducklings, what’s more, infection of GPV in muscovy ducklings generally produce the higher morbidity and mortality than infection of MDPV. Undoubtedly, the differential pathogenicity exhibited in muscovy ducklings and goslings caused by MDPV and GPV results from the genome differences between two viruses, but which genome regions actually contribute the differential pathogenicity for the two intimate waterfowl parvoviruses are not understood clearly..In a preliminary study, the recombinant plasmid containing the entire genome of the virulent strain LH of GPV was constructed, and the infectious virus carrying the genetic marker was rescued successfully by transfection of the pLH plasmid in embryonated goose eggs via the chorioallantic membrane route. In this study, we plan to further construct the infectious plasmid pNY that contain the complete genome of the virulent strain NY of MDPV, and perform the rescue in embryonated muscovy duck eggs. The whole genome of strain NY will be sequenced and compared with that of strain LH. The highly variable regions distributed in the genomes that may play the key roles in differential pathogenicity between NY and LH will be identified for further analysis. The variable DNA regions will be swapped between the plasmid pNY and pLH, resulting in a series of chimeric plasmids. After transfection of the chimeric plasmids in embryonated muscovy ducks or goose eggs, the recombinant chimeric viruses will be rescued. Animal challenge experiments will be performed on 1-day-old muscovy ducklings or goslings to evaluate the pathogenicity of the chimeric viruses, and the experimental results will allow us to map the DNA regions correlated with the differential pathogenicity of MDPV and GPV. Based on the obtained data and analysis, we will continue to implement mutations on key amino acids or nucleotides sites, and testify their roles in the pathogenicity. Elucidation of the molecular basis of the differential pathogenicity of MDPV and GPV will lay a solid foundation for us to further explore the pathogenesis of waterfowl parvoviruses.