Department of Veterinary Diagnostic and Production Animal Medicine, College of Veterinary Medicine, Iowa State University, 1600 S. 16th Street, Ames, IA, 50011, USA.
Vet Res Commun. 2012 Sep;36(3):187-93. doi: 10.1007/s11259-012-9524-z. Epub 2012 Mar 3.
Xenotransplantation of tissues from transgenic pigs with desired genetic modifications such as CD46 expression help minimize xenograft rejections. However, CD46 is a known receptor for some viruses. In this study, pigs transgenic for human CD46 (CD46-TG) and appropriate non-transgenic (non-TG) control pigs were utilized to determine possible differences in the level of replication and shedding of porcine circovirus type 2 (PCV2). Non-TG and CD46-TG were blocked by transgenic status and randomly divided into three groups: Non-TG negative controls (n = 3), non-TG-PCV2 (n = 10; PCV2a = 5, PCV2b = 5), and CD46-TG-PCV2 (n = 6; PCV2a = 3, PCV2b = 3). Blood, oral, nasal and fecal swabs were collected at regular intervals from the day of arrival until 70 days post inoculation (DPI). All samples were tested by quantitative real-time PCR for the presence of PCV2 DNA and serum was tested for presence of PCV2 antibodies by ELISA. Overall, the main effects "transgenic status" and "PCV2 subtype" had no influence on degree of PCV2 viremia and shedding or the anti-PCV2 humoral immune response in CD46-TG-PCV2 pigs compared to non-TG-PCV2 pigs. Differences in PCV2 concentrations between non-TG-PCV2 and CD46-TG-PCV2 pigs were minimal and limited to DPI 35 in sera, DPI 7 in fecal swabs and DPI 5 in nasal swabs when CD46-TG-PCV2 pigs had significantly higher concentrations of PCV2 DNA. At DPI 1, CD46-TG-PCV2 pigs had significantly lower concentrations of PCV2 DNA in oral swabs. Under the study conditions, the presence of human CD46 in transgenic pigs had no effect on PCV2 infection in otherwise healthy pigs capable of a normal immune response.
转染具有所需遗传修饰(如 CD46 表达)的组织的异种移植有助于最大限度地减少异种移植物排斥。然而,CD46 是一些病毒的已知受体。在这项研究中,转染人 CD46 的猪(CD46-TG)和适当的非转基因(非-TG)对照猪被用于确定猪圆环病毒 2 (PCV2)的复制和脱落水平可能存在的差异。非-TG 和 CD46-TG 因转基因状态而被阻断,并随机分为三组:非-TG 阴性对照(n = 3)、非-TG-PCV2(n = 10;PCV2a = 5,PCV2b = 5)和 CD46-TG-PCV2(n = 6;PCV2a = 3,PCV2b = 3)。从接种之日起至接种后 70 天(DPI),定期采集血液、口腔、鼻腔和粪便拭子。所有样本均通过定量实时 PCR 检测 PCV2 DNA 的存在,通过 ELISA 检测血清中 PCV2 抗体的存在。总体而言,与非-TG-PCV2 猪相比,“转基因状态”和“PCV2 亚型”的主要影响因素对 CD46-TG-PCV2 猪的 PCV2 血症和脱落程度或抗 PCV2 体液免疫反应没有影响。非-TG-PCV2 和 CD46-TG-PCV2 猪之间的 PCV2 浓度差异最小,仅限于血清 DPI 35、粪便拭子 DPI 7 和鼻腔拭子 DPI 5,当 CD46-TG-PCV2 猪的 PCV2 DNA 浓度显著更高时。在 DPI 1 时,CD46-TG-PCV2 猪口腔拭子中的 PCV2 DNA 浓度显著较低。在研究条件下,在能够正常免疫反应的健康猪中,转染猪的人 CD46 的存在对 PCV2 感染没有影响。