Kintner R L, Allan R W, Brandt C R
Department of Medical Microbiology, University of Wisconsin-Madison Medical School, USA.
Arch Virol. 1995;140(2):231-44. doi: 10.1007/BF01309859.
Mixed infections with different strains of herpes simplex virus type 1 (HSV-1) may result in more severe disease than infection with either strain alone. This phenomenon is important because it may facilitate the identification of virulence genes through the transfer of virulence determinants between complementing strains, and it may pose a problem in the use of attenuated HSV strains for vaccines and gene delivery vectors. In this study, we have compared the percentage of recombinants present after mixed infection with HSV-1 strains OD4 and 994 in vitro and in vivo. After corneal inoculation, we found that 74% of randomly picked isolates from the trigeminal ganglia were recombinants, compared with 59% from the cornea. Twenty-six percent of randomly picked isolates were recombinant following mixed infection of Vero cells in vitro. Seventeen recombinant strains isolated from the in vivo mixed infections were assayed for ocular virulence, and they were found to exhibit a wide range of virulence phenotypes. The presence of virulent recombinants suggests that recombination plays a role in the increased disease observed in this mixed infection, and the broad range of virulence indicates that there may be multiple genetic factors involved in the increased virulence observed after mixed infection with these two strains. The recombinants were also tested for their ability to grow in NIH 3T3 fibroblasts, and though some correlation was observed between growth in vitro and ability to cause ocular disease, improved growth in murine cells does not sufficiently explain the increased virulence observed in some recombinants.
单纯疱疹病毒1型（HSV-1）不同毒株的混合感染可能导致比单独感染任何一种毒株更严重的疾病。这一现象很重要，因为它可能通过互补毒株之间毒力决定因素的转移来促进毒力基因的鉴定，并且在使用减毒HSV毒株作为疫苗和基因递送载体时可能会带来问题。在本研究中，我们比较了HSV-1毒株OD4和994在体外和体内混合感染后重组体出现的百分比。角膜接种后，我们发现从三叉神经节随机挑选的分离株中有74%是重组体，而角膜分离株中这一比例为59%。体外Vero细胞混合感染后，随机挑选的分离株中有26%是重组体。对从体内混合感染中分离出的17株重组毒株进行了眼毒力测定，发现它们表现出广泛的毒力表型。强毒重组体的存在表明重组在这种混合感染中观察到的疾病加重中起作用，毒力范围广泛表明在这两种毒株混合感染后观察到的毒力增加可能涉及多个遗传因素。还测试了重组体在NIH 3T3成纤维细胞中的生长能力，尽管在体外生长与引起眼部疾病的能力之间观察到了一些相关性，但在鼠细胞中生长的改善并不能充分解释在一些重组体中观察到的毒力增加。
