Tri-Institutional Training Program in Laboratory Animal Medicine and Science, Memorial Sloan Kettering Cancer Center, Weill Cornell Medicine, and The Rockefeller University; Current affiliation: Institute of Comparative Medicine, Columbia University ; ;
Tri-Institutional Training Program in Laboratory Animal Medicine and Science, Memorial Sloan Kettering Cancer Center, Weill Cornell Medicine, and The Rockefeller University; Center for Comparative Medicine and Pathology, Memorial Sloan Kettering Cancer Center and Weill Cornell Medicine, New York.
Comp Med. 2022 Dec 1;72(6):376-385. doi: 10.30802/AALAS-CM-22-000066.
Mouse kidney parvovirus (MKPV), the etiology of murine inclusion body nephropathy, has been identified globally in mice used for research, with an estimated prevalence of 10% in academic colonies. In immunodeficient strains, MKPV causes significant morbidity and mortality, and severe renal pathology. In contrast, in immunocompetent mice, the infection is subclinical and causes minimal pathology. We investigated viral infectivity and shedding in inbred C57BL/6NCrl (B6), outbred Crl:CD1(ICR) (CD1), and highly immunocompromised NOD. Cg /SzJ (NSG) mice. Four doses, ranging from 1.16 × 10 3 to 1.16 × 10 6 viral copies per microliter, of an MKPV inoculum were administered oronasally to 3 mice per dose per mouse type. All 3 types (B6, CD1, and NSG) had persistent infection with prolonged shedding in urine and feces. Viral copy number in the urine generally increased over time, while shedding in the feces was more variable. Among the 3 populations, CD1 mice developed viral shedding in urine earliest (4 wk after inoculation) and at higher levels (greater than 1 × 10 7 viral copies per microliter). B6 mice become viruric later (7 wk after inoculation), with lesser virus shed (1 × 10 6 viral copies per microliter or less). In CD1 and B6 mice, peak urine shedding occurred at 11 to 14 wk after inoculation, after which levels gradually declined until 35 wk after inoculation (study endpoint). In contrast, NSG mice did not become viruric until 10 wk after inoculation and continued to shed large amounts of virus (greater than 1 × 10 viral copies per microliter) in urine until the study endpoint. Two commercial immunofluorescent serologic assays failed to detect serum antibodies to MKPV nonstructural protein 1 as late as 58 wk after inoculation, whereas immunohistochemistry of infected renal tissue successfully detected anti-MKPV serum antibodies. These results increase our knowledge of the biology of MKPV and have practical application for development of effective screening programs for this pathogen.
鼠肾细小病毒(MKPV)是导致鼠包涵体肾病的病因,已在用于研究的小鼠中在全球范围内被鉴定出来,在学术群体中的流行率估计为 10%。在免疫缺陷品系中,MKPV 会导致严重的发病率和死亡率,并引起严重的肾脏病理变化。相比之下,在免疫功能正常的小鼠中,感染是亚临床的,仅引起最小的病理变化。我们研究了传染性和脱落的同基因 C57BL/6NCrl(B6)、远交 Crl:CD1(ICR)(CD1)和高度免疫缺陷的 NOD.Cg /SzJ(NSG)小鼠中的病毒感染性和脱落。将 1.16×103 至 1.16×106 个病毒拷贝/微升的 MKPV 接种物的 4 个剂量分别给予每只小鼠 3 只小鼠,每只小鼠 3 个剂量。所有 3 种类型(B6、CD1 和 NSG)均持续感染,尿液和粪便中的脱落时间延长。尿液中的病毒数量通常随时间增加,而粪便中的脱落则更为多变。在这 3 个群体中,CD1 小鼠最早开始在尿液中排出病毒(接种后 4 周),并且水平更高(超过 1×107 个病毒拷贝/微升)。B6 小鼠随后出现病毒血症(接种后 7 周),排出的病毒较少(1×106 个病毒拷贝/微升或更少)。在 CD1 和 B6 小鼠中,接种后 11 至 14 周达到尿液脱落高峰,此后水平逐渐下降,直到接种后 35 周(研究终点)。相比之下,NSG 小鼠直到接种后 10 周才出现病毒血症,并继续在尿液中大量排出病毒(超过 1×107 个病毒拷贝/微升),直到研究终点。两种商业免疫荧光血清学检测均未能检测到接种后长达 58 周的血清抗体对 MKPV 非结构蛋白 1 的反应,而感染肾组织的免疫组化成功检测到抗-MKPV 血清抗体。这些结果增加了我们对 MKPV 生物学的认识,并且对这种病原体的有效筛选计划的发展具有实际应用价值。