Voronin Yegor, Overbaugh Julie, Emerman Michael
Division of Human Biology, Mail Stop C2-023, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave. N, Seattle, WA 98109-1024, USA.
J Virol. 2005 Dec;79(24):15091-8. doi: 10.1128/JVI.79.24.15091-15098.2005.
Simian immunodeficiency virus (SIV) has been shown to progress through a number of changes that lead to the emergence of pathogenic viral variants in macaques initially infected with a mildly cytopathic variant, SIVMneCL8. One of these late-stage isolates, SIVMne170, replicates to high levels in vivo and causes a rapid disease course when reintroduced into naïve macaques, resulting in a viral set point up to 3,000-fold higher than the set point of the parental virus, SIVMneCL8. However, in cell culture both viruses replicate with similar kinetics. One major difference between in vivo and in vitro cultures is the life span of the infected cells. Here, we manipulated the life span of infected cells in vitro, and we show that the fitness of SIVMne170 in cultures with a limited cell life span dramatically increased compared to its fitness in cultures with a nonlimited life span of cells. The increase in fitness was at least partially due to the fact that the rapid turnover system eliminates the negative influence of the cytopathic effects associated with replication of SIVMne170. Because the relative fitness of SIVMneCL8 and SIVMne170 observed in the rapid turnover system more accurately reflects their fitness in vivo, the system represents an improved approach to comparing relative fitness of viruses.
猿猴免疫缺陷病毒（SIV）已被证明会经历一系列变化，这些变化导致最初感染轻度细胞病变变体SIVMneCL8的猕猴体内出现致病性病毒变体。其中一种晚期分离株SIVMne170在体内能大量复制，当重新引入未感染的猕猴体内时会导致疾病快速发展，其病毒载量峰值比亲本病毒SIVMneCL8的病毒载量峰值高3000倍。然而，在细胞培养中，两种病毒的复制动力学相似。体内培养和体外培养的一个主要区别在于被感染细胞的寿命。在此，我们在体外操纵被感染细胞的寿命，结果表明，与在细胞寿命无限制的培养物中相比，SIVMne170在细胞寿命有限的培养物中的适应性显著提高。适应性的提高至少部分归因于快速周转系统消除了与SIVMne170复制相关的细胞病变效应的负面影响。由于在快速周转系统中观察到的SIVMneCL8和SIVMne170的相对适应性更准确地反映了它们在体内的适应性，该系统代表了一种比较病毒相对适应性的改进方法。
