Bhadra Sanchita, Lozano Mary M, Payne Shelley M, Dudley Jaquelin P
Section of Molecular Genetics and Microbiology and Institute for Cellular and Molecular Biology, University of Texas at Austin, Austin, Texas, United States of America.
PLoS Pathog. 2006 Dec;2(12):e128. doi: 10.1371/journal.ppat.0020128.
Most inbred mice carry germline proviruses of the retrovirus, mouse mammary tumor virus (MMTV) (called Mtvs), which have multiple replication defects. A BALB/c congenic mouse strain lacking all endogenous Mtvs (Mtv-null) was resistant to MMTV oral and intraperitoneal infection and tumorigenesis compared to wild-type BALB/c mice. Infection of Mtv-null mice with an MMTV-related retrovirus, type B leukemogenic virus, also resulted in severely reduced viral loads and failure to induce T-cell lymphomas, indicating that resistance is not dependent on expression of a superantigen (Sag) encoded by exogenous MMTV. Resistance to MMTV in Mtv-null animals was not due to neutralizing antibodies. Further, Mtv-null mice were resistant to rapid mortality induced by intragastric inoculation of the Gram-negative bacterium, Vibrio cholerae, but susceptibility to Salmonella typhimurium was not significantly different from BALB/c mice. Susceptibility to both MMTV and V. cholerae was reconstituted by the presence of any one of three endogenous Mtvs located on different chromosomes and was associated with increased pathogen load. One of these endogenous proviruses is known to encode only Sag. Therefore, Mtv-encoded Sag appears to provide a unique genetic susceptibility to specific viruses and bacteria. Since human endogenous retroviruses also encode Sags, these studies have broad implications for pathogen-induced responses in mice and humans.
大多数近交系小鼠携带逆转录病毒小鼠乳腺肿瘤病毒（MMTV）的种系前病毒（称为Mtv），这些前病毒存在多种复制缺陷。与野生型BALB/c小鼠相比，一种缺乏所有内源性Mtv（Mtv缺失）的BALB/c同源近交系小鼠对MMTV经口和腹腔感染及肿瘤发生具有抗性。用一种与MMTV相关的逆转录病毒B型白血病病毒感染Mtv缺失小鼠，也会导致病毒载量严重降低且无法诱导T细胞淋巴瘤，这表明抗性并不依赖于外源性MMTV编码的超抗原（Sag）的表达。Mtv缺失动物对MMTV的抗性并非由于中和抗体。此外，Mtv缺失小鼠对经胃内接种革兰氏阴性菌霍乱弧菌诱导的快速死亡具有抗性，但对鼠伤寒沙门氏菌的易感性与BALB/c小鼠无显著差异。位于不同染色体上的三种内源性Mtv中的任何一种的存在都可恢复对MMTV和霍乱弧菌的易感性，且与病原体载量增加有关。已知其中一种内源性前病毒仅编码Sag。因此，Mtv编码的Sag似乎赋予了对特定病毒和细菌独特的遗传易感性。由于人类内源性逆转录病毒也编码Sag，这些研究对小鼠和人类中病原体诱导的反应具有广泛的意义。
