Lausch R N, Su Y H, Ritchie M, Oakes J E
University of South Alabama, College of Medicine, Department of Microbiology and Immunology, Mobile 36688.
Curr Eye Res. 1991;10 Suppl:39-45. doi: 10.3109/02713689109020356.
An intertypic recombinant isolated from rabbit kidney cells following co-transfection of HSV-1(17) and HSV-2(186) DNA failed to induce overt ocular pathology when inoculated onto the murine sacrificed cornea at concentrations as high as 10(7) PFU per eye. In contrast, both parents induced corneal disease at a 1000-fold lower dose. The reason(s) for the failure of the intertypic recombinant, designated RO25X, to induce corneal pathology was investigated. It was found that the recombinant was 100-fold more sensitive to the inhibitory effects of interferon (IFN) alpha/beta than the parent strains in corneal button growth studies in vitro. R025X readily grew in cultured mouse corneal fibroblasts at a low multiplicity of infection. However, the peak titer was approximately 8-fold lower than that of strain 17. Addition of rabbit anti-IFN alpha/beta to the culture medium resulted in a 4 to 5-fold increase in infectious titer compared to its growth in the absence of antiserum. Most significantly, when mice were pre-treated in vivo with anti-IFN alpha/beta 24 hours prior to virus corneal infection, 67% of the recipients developed moderate to severe stromal keratitis, whereas none of the controls developed corneal pathology. Blepharitis was also significantly increased in incidence and severity in the antiserum treated hosts. We conclude that the inability of R025X to induce ocular disease was due, at least in part, to the inhibitory effects of interferon produced in response to infection.
在将单纯疱疹病毒1型（17株）和单纯疱疹病毒2型（186株）DNA共转染兔肾细胞后分离得到的一株型间重组体，当以高达每眼10⁷蚀斑形成单位（PFU）的浓度接种到处死的小鼠角膜上时，未能诱发明显的眼部病变。相比之下，两种亲代病毒在剂量低1000倍时就能诱发角膜疾病。对这株名为RO25X的型间重组体未能诱发角膜病变的原因进行了研究。发现在体外角膜植块生长研究中，该重组体对α/β干扰素（IFN）的抑制作用比亲代毒株敏感100倍。R025X在低感染复数下能在培养的小鼠角膜成纤维细胞中顺利生长。然而，其峰值滴度比17株约低8倍。与在无抗血清情况下生长相比，向培养基中添加兔抗α/β干扰素可使感染滴度增加4至5倍。最显著的是，在病毒角膜感染前24小时用抗α/β干扰素对小鼠进行体内预处理，67%的受体出现中度至重度基质性角膜炎，而对照组均未出现角膜病变。在抗血清处理的宿主中，睑缘炎的发生率和严重程度也显著增加。我们得出结论，R025X不能诱发眼部疾病至少部分是由于感染后产生的干扰素的抑制作用。
