Department of Microbiology, University of Chicago , Chicago, Illinois, USA.
Committee on Immunology, University of Chicago , Chicago, Illinois, USA.
J Virol. 2023 Aug 31;97(8):e0068523. doi: 10.1128/jvi.00685-23. Epub 2023 Aug 14.
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 () 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.
宿主的遗传构成会影响对病毒感染的不同反应。由于无法进行原理验证研究，因此研究人类对逆转录病毒的抗性变得复杂。近交系小鼠具有一系列对逆转录病毒易感的表型，是鉴定和描述抗性机制及其遗传基础的理想工具。YBR/Ei 小鼠感染了 Mouse Mammary Tumor Virus，这是一种黏膜传播的鼠类逆转录病毒，但会从其家族中消除该病毒。病毒消除与缺乏病毒特异性新生儿口腔耐受性相关，这是阻止易感小鼠抗病毒反应的主要机制。病毒控制与中和抗体、细胞毒性 CD8 T 细胞、NK 细胞和 NK T 细胞无关，这些是对抗逆转录病毒的最佳特征性抗性机制。我们确定了一个单一的、显性基因座控制着这种抗性机制，我们暂时将其命名为病毒滴度衰减 ()，并将其映射到染色体 18 的远端区域。重要性阐明介导对逆转录病毒的抗性的机制对于人类健康具有根本重要性，因为它最终将导致了解个体对微生物感染易感性的遗传差异。
