PDF(Pubmed)
Abstract：
Differential responses to viral infections are influenced by the genetic makeup of the host. Studies of resistance to retroviruses in human populations are complicated due to the inability to conduct proof-of-principle studies. Inbred mouse lines, which have a range of susceptible phenotypes to retroviruses, are an ideal tool to identify and characterize mechanisms of resistance and define their genetic underpinnings. YBR/Ei mice become infected with Mouse Mammary Tumor Virus, a mucosally transmitted murine retrovirus, but eliminate the virus from their pedigrees. Virus elimination correlates with a lack of virus-specific neonatal oral tolerance, which is a major mechanism for blocking the anti-virus response in susceptible mice. Virus control is unrelated to virus-neutralizing antibodies, cytotoxic CD8+ T cells, NK cells, and NK T cells, which are the best characterized mechanisms of resistance to retroviruses. We identified a single, dominant locus that controls the resistance mechanism, which we provisionally named attenuation of virus titers (Avt) and mapped to the distal region of chromosome 18. IMPORTANCE Elucidation of the mechanism that mediates resistance to retroviruses is of fundamental importance to human health, as it will ultimately lead to knowledge of the genetic differences among individuals in susceptibility to microbial infections.
摘要：
对病毒感染的差异反应受宿主遗传组成的影响。由于无法进行原理验证研究，因此在人群中对逆转录病毒的抗性研究很复杂。近交系小鼠,它们具有一系列对逆转录病毒易感的表型，是鉴定和表征抗性机制并定义其遗传基础的理想工具。YBR/Ei小鼠感染了小鼠乳腺肿瘤病毒，一种粘膜传播的鼠逆转录病毒，但是从他们的家谱中排除病毒.病毒消除与缺乏病毒特异性新生儿口服耐受性相关，这是阻断易感小鼠抗病毒反应的主要机制。病毒控制与病毒中和抗体无关，细胞毒性CD8+T细胞，NK细胞,和NKT细胞，这是抗逆转录病毒的最佳特征机制。我们确定了一个人，控制抗性机制的显性位点，我们暂时将其命名为病毒滴度减毒（Avt），并定位到18号染色体的远端区域。重要性阐明介导逆转录病毒抗性的机制对人类健康至关重要，因为它最终将导致对微生物感染易感性的个体之间的遗传差异的知识。
