Greenlee J E, Phelps R C, Stroop W G
Neurology and Research Services, Veterans Administration Medical Center, Salt Lake City, Utah.
Microb Pathog. 1991 Oct;11(4):237-47. doi: 10.1016/0882-4010(91)90028-9.
K virus, a murine papovavirus, produces a lethal pneumonia in newborn mice. Animals surviving acute illness develop a persistent infection which reactivates under conditions of immunosuppression. The present study was conducted to identify the cell populations which support persistent K virus infection and to determine the cell populations in which this persistent infection is reactivated during immunosuppression. Mice inoculated by the oral route with 100 50% newborn mouse lethal doses (LD50) of K virus at 14 days of age were followed over a period of 7 months. The distribution of infection was studied by virus assay, immunohistochemistry, and in situ nucleic acid hybridization methods. Viral replication during the acute phase of infection was confined to pulmonary and systemic vascular endothelial cells, as well as to scattered, apparently lymphoid cells within spleens. Beginning 2 months after inoculation, however, specific hybridization for K virus nucleic acids was detected in rare renal tubular epithelial cells, and by 6 months after inoculation renal tubular epithelial cells represented the major site of viral persistence. Positive cells were frequently present in groups of two or more, and a minority of positive cells also expressed viral capsid (V) antigen. Immunosuppression with cyclophosphamide resulted in reactivation of infection, with highest titers of virus being detected in kidneys and with increased numbers of renal tubular epithelial cells expressing viral capsid antigen. Capsid antigen was also detected in rare endothelial cells in kidneys, livers and lungs of these immunosuppressed mice. Although K virus behaves as an endotheliotrope during acute infection, the major site of K virus persistence and reactivation, the renal tubular epithelial cell, is similar to that involved during persistent infection by polyoma virus in mice, SV40 virus in monkeys, and BK and JC viruses in man. The observation that persistently infected renal tubular epithelial cells occur in groups of two or more and occasionally express capsid antigen suggests that virus may persist as a productive infection which is confined by antiviral antibody but maintains itself by cell-to-cell-spread. The present study represents the first instance in which the cell populations which support infection by a member of the polyomavirus subgroup in its natural host have been defined during acute, persistent, and reactivated infection.
K病毒是一种鼠乳头瘤病毒，可在新生小鼠中引发致死性肺炎。急性疾病幸存者会发展为持续性感染，并在免疫抑制条件下重新激活。本研究旨在确定支持K病毒持续性感染的细胞群体，并确定在免疫抑制期间这种持续性感染被重新激活的细胞群体。对14日龄经口接种100个50%新生小鼠致死剂量（LD50）K病毒的小鼠进行了7个月的跟踪观察。通过病毒检测、免疫组织化学和原位核酸杂交方法研究感染的分布情况。感染急性期的病毒复制局限于肺和全身血管内皮细胞，以及脾脏内散在的、明显为淋巴细胞的细胞。然而，接种后2个月开始，在罕见的肾小管上皮细胞中检测到K病毒核酸的特异性杂交，接种后6个月时，肾小管上皮细胞成为病毒持续性感染的主要部位。阳性细胞常以两个或更多细胞的群体形式存在，少数阳性细胞还表达病毒衣壳（V）抗原。用环磷酰胺进行免疫抑制导致感染重新激活，在肾脏中检测到最高滴度的病毒，且表达病毒衣壳抗原的肾小管上皮细胞数量增加。在这些免疫抑制小鼠的肾脏、肝脏和肺的罕见内皮细胞中也检测到了衣壳抗原。尽管K病毒在急性感染期间表现为嗜内皮性，但K病毒持续性感染和重新激活的主要部位——肾小管上皮细胞，与小鼠中多瘤病毒、猴中SV40病毒以及人类中BK和JC病毒持续性感染所涉及的部位相似。持续性感染的肾小管上皮细胞以两个或更多细胞群体形式出现且偶尔表达衣壳抗原这一观察结果表明，病毒可能以生产性感染的形式持续存在，这种感染受到抗病毒抗体的限制，但通过细胞间传播维持自身。本研究首次明确了在自然宿主中支持多瘤病毒亚组成员感染的细胞群体在急性、持续性和重新激活感染期间的情况。
