Foster R G, Lian J B, Stein G, Robinson H L
Department of Molecular Genetics and Microbiology, University of Massachusetts Medical Center, Worcester 01655.
Virology. 1994 Nov 15;205(1):179-87. doi: 10.1006/viro.1994.1633.
Avian leukosis virus (ALV)-induced osteopetrosis is caused by the abnormal growth and differentiation of osteoblasts. To evaluate the role of infection in osteopetrosis induction, the replication of an osteopetrosis-inducing virus (Br21) has been compared in osteopetrotic bone, calvarial-derived osteoblasts, and chick embryo fibroblasts. Much higher levels of infection occurred in diseased bone than in the cultures. Severe cases of osteopetrosis contained 10 times more viral DNA, 30 times more mature capsid protein, 5 to 10 times more Gag precursor protein, and 2 to 3 times more Env protein than the infected cultures. Virus replication in the cultured osteoblasts was similar to that in fibroblasts except for a distinctive asymmetric localization of Gag proteins. In osteopetrotic chickens, bones became atypically enlarged and sera contained elevated levels of osteoblast differentiation markers (alkaline phosphatase and osteocalcin). In cultures, infections did not affect the growth or differentiation of osteoblasts. Thus, the infected cultures lacked aspects of the bone environment that support both the high levels of infection and the aberrant function of osteoblasts characteristic of ALV-induced osteopetrosis.
禽白血病病毒(ALV)诱导的骨质石化是由成骨细胞的异常生长和分化引起的。为了评估感染在骨质石化诱导中的作用,已经比较了一种诱导骨质石化的病毒(Br21)在骨质石化骨、颅骨来源的成骨细胞和鸡胚成纤维细胞中的复制情况。患病骨骼中的感染水平远高于培养物中的感染水平。严重的骨质石化病例中,病毒DNA含量比感染的培养物多10倍,成熟衣壳蛋白多30倍,Gag前体蛋白多5至10倍,Env蛋白多2至3倍。培养的成骨细胞中的病毒复制与成纤维细胞中的相似,只是Gag蛋白有独特的不对称定位。在患骨质石化的鸡中,骨骼异常增大,血清中骨细胞分化标志物(碱性磷酸酶和骨钙素)水平升高。在培养物中,感染不影响成骨细胞的生长或分化。因此,感染的培养物缺乏支持高水平感染和成骨细胞异常功能(这是ALV诱导的骨质石化的特征)的骨环境因素。