Takeuchi Y, Porter C D, Strahan K M, Preece A F, Gustafsson K, Cosset F L, Weiss R A, Collins M K
Chester Beatty Laboratories, Institute of Cancer Research, London, UK.
Nature. 1996 Jan 4;379(6560):85-8. doi: 10.1038/379085a0.
Mammalian C-type retroviruses are inactivated by human serum, following triggering of the classical complement cascade. This may have inhibited transmission to humans of C-type oncoviruses from other mammals. Indeed, the retroviruses human immunodeficiency virus and human T-cell leukaemia virus are resistant to human complement. Antibody-independent activation of human C1q, the first component of the classical pathway, by retroviral envelope proteins has been described. However, retroviruses produced from human cells are resistant to inactivation by human complement and human serum is known to contain antibodies directed against carbohydrates on retroviral envelopes. Gal(alpha 1-3)Gal terminal carbohydrates are expressed by most mammals but are absent in humans, which lack a functional (alpha 1-3)galactosyltransferase gene. Here, we demonstrate that anti-Gal(alpha 1-3)Gal antibodies in human serum inactivate retroviruses produced from animal cells. Expression of porcine (alpha 1-3)galactosyltransferase in human cells renders the cells and the retroviruses they produce sensitive to human serum.
在经典补体级联反应被触发后，哺乳动物C型逆转录病毒会被人血清灭活。这可能抑制了C型肿瘤病毒从其他哺乳动物向人类的传播。事实上，逆转录病毒人类免疫缺陷病毒和人类T细胞白血病病毒对人补体具有抗性。已经有关于逆转录病毒包膜蛋白独立于抗体激活经典途径的第一成分人C1q的描述。然而，从人细胞产生的逆转录病毒对人补体的灭活具有抗性，并且已知人血清中含有针对逆转录病毒包膜上碳水化合物的抗体。大多数哺乳动物表达Gal(α1-3)Gal末端碳水化合物，但人类缺乏功能性的(α1-3)半乳糖基转移酶基因，因此不存在这种碳水化合物。在这里，我们证明人血清中的抗Gal(α1-3)Gal抗体可灭活从动物细胞产生的逆转录病毒。猪(α1-3)半乳糖基转移酶在人细胞中的表达使细胞及其产生的逆转录病毒对人血清敏感。
