Institute of Virology, Freie Universität Berlin, Berlin, Germany.
Department of Pathology, University of Cambridge, Cambridge, United Kingdom.
Front Immunol. 2022 May 27;13:908305. doi: 10.3389/fimmu.2022.908305. eCollection 2022.
The major histocompatibility complex (MHC) is crucial for appropriate immune responses against invading pathogens. Chickens possess a single predominantly-expressed class I molecule with strong associations between disease resistance and MHC haplotype. For Marek's disease virus (MDV) infections of chickens, the MHC haplotype is one of the major determinants of genetic resistance and susceptibility. VALO specific pathogen free (SPF) chickens are widely used in biomedical research and vaccine production. While valuable findings originate from MDV infections of VALO SPF chickens, their MHC haplotypes and associated disease resistance remained elusive. In this study, we used several typing systems to show that VALO SPF chickens possess MHC haplotypes that include B9, B9:02, B15, B19 and B21 at various frequencies. Moreover, we associate the MHC haplotypes to MDV-induced disease and lymphoma formation and found that B15 homozygotes had the lowest tumor incidence while B21 homozygotes had the lowest number of organs with tumors. Finally, we found transmission at variable levels to all contact birds except B15/B21 heterozygotes. These data have immediate implications for the use of VALO SPF chickens and eggs in the life sciences and add another piece to the puzzle of the chicken MHC complex and its role in infections with this oncogenic herpesvirus.
主要组织相容性复合体 (MHC) 对于针对入侵病原体的适当免疫反应至关重要。鸡只拥有单一主要表达的 I 类分子,其与疾病抗性和 MHC 单倍型之间存在强烈关联。对于鸡马立克氏病病毒 (MDV) 的感染,MHC 单倍型是遗传抗性和易感性的主要决定因素之一。VALO 特定病原体无特定病原体 (SPF) 鸡被广泛用于生物医学研究和疫苗生产。虽然 VALO SPF 鸡的 MDV 感染产生了有价值的发现,但它们的 MHC 单倍型和相关的疾病抗性仍然难以捉摸。在这项研究中,我们使用了几种分型系统来表明 VALO SPF 鸡具有包括 B9、B9:02、B15、B19 和 B21 在内的各种频率的 MHC 单倍型。此外,我们将 MHC 单倍型与 MDV 诱导的疾病和淋巴瘤形成相关联,发现 B15 纯合子的肿瘤发病率最低,而 B21 纯合子的器官肿瘤数量最少。最后,我们发现除了 B15/B21 杂合子之外,所有接触的鸟类都以不同的水平进行了传播。这些数据立即对 VALO SPF 鸡和鸡蛋在生命科学中的使用产生了影响,并为鸡 MHC 复合体及其在这种致癌疱疹病毒感染中的作用增添了另一个谜题。