Ghiasi H, Perng G C, Hofman F M, Cai S, Nesburn A B, Wechsler S L
Ophthalmology Research, Cedars-Sinai Burn and Allen Research Institute, CSMC-Davis Building, Room 5072, 8700 Beverly Boulevard, Los Angeles, California, 90048, USA.
Virology. 1999 Jun 5;258(2):208-16. doi: 10.1006/viro.1999.9710.
Ocular herpes simplex virus type 1 (HSV-1) infection of MHC-II-deficient mice (AO/Obeta mice) or their parental C57BL/6J wild-type mice resulted in the establishment of typical HSV-1 latent infections in the trigeminal ganglia (TG) of the surviving mice by day 28 postinfection. Latency was characterized by the complete absence of infectious virus in TG extracts, the ability to recover latent virus only following prolonged tissue culture cultivation of explanted TG, and the presence of HSV-1 DNA in TG extracts. When mice were vaccinated prior to ocular HSV-1 challenge, latency appeared unaltered in the C57BL/6J wild-type mice. However, in AO/Obeta mice, clearance of virus from the TG appeared to be seriously impaired, resulting in a chronic productive infection, rather than a latent infection. Infectious virus was readily detected in TG extracts of vaccinated AO/Obeta mice until at least 63 days postinfection. Glycoprotein B mRNA was also readily detected, confirming continued viral transcription. These chronic infections occurred regardless of whether the AO/Obeta mice were vaccinated with HSV-1-specific antigens (i.e., live HSV-1 strain KOS, recombinantly expressed HSV-1 glycoprotein D plus Freund's adjuvant, or a mixture of seven recombinantly expressed HSV-1 glycoproteins plus adjuvant) or non-HSV-1-specific antigens (i.e., tissue culture medium plus 5% fetal bovine serum, the expression vector plus adjuvant, or adjuvant alone). Passive transfer of HSV-1 neutralizing antibody to vaccinated AO/Obeta mice between days 0 and 28 post-ocular challenge did not clear infectious virus from the TG. Passive transfer of anti-HSV-1 antibody or purified naive mouse serum to unvaccinated AO/Obeta mice on days 3 or 6 post-HSV-1 ocular challenge also resulted in chronic, rather than latent, infection of the TG. Passive transfer of naive sera from B-cell-deficient mice or injection of keyhole limpet hemocyanin or purified IgG, but not PBS or dextran, 3 days after HSV-1 challenge also resulted in chronic infection of the TG.
将1型单纯疱疹病毒（HSV-1）感染MHC-II缺陷小鼠（AO/Obeta小鼠）或其亲代C57BL/6J野生型小鼠，在感染后第28天，存活小鼠的三叉神经节（TG）中会建立典型的HSV-1潜伏感染。潜伏感染的特征为：TG提取物中完全没有传染性病毒；只有在对取出的TG进行长时间组织培养后才能恢复潜伏病毒；TG提取物中存在HSV-1 DNA。当小鼠在眼部受到HSV-1攻击之前接种疫苗时，C57BL/6J野生型小鼠的潜伏感染情况似乎未发生改变。然而，在AO/Obeta小鼠中，病毒从TG的清除似乎受到严重损害，导致慢性增殖性感染，而非潜伏感染。在接种疫苗的AO/Obeta小鼠的TG提取物中，至少在感染后63天仍能轻易检测到传染性病毒。还能轻易检测到糖蛋白B mRNA，证实病毒在持续转录。无论AO/Obeta小鼠是用HSV-1特异性抗原（即活HSV-1毒株KOS、重组表达的HSV-1糖蛋白D加弗氏佐剂，或七种重组表达的HSV-1糖蛋白加佐剂的混合物）还是非HSV-1特异性抗原（即组织培养基加5%胎牛血清、表达载体加佐剂或单独的佐剂）进行接种，都会发生这些慢性感染。在眼部攻击后第0天至第28天，将HSV-1中和抗体被动转移到接种疫苗的AO/Obeta小鼠体内，并不能清除TG中的传染性病毒。在HSV-1眼部攻击后第3天或第6天，将抗HSV-1抗体或纯化的未免疫小鼠血清被动转移到未接种疫苗的AO/Obeta小鼠体内，也会导致TG的慢性感染，而非潜伏感染。在HSV-1攻击后3天，将B细胞缺陷小鼠的未免疫血清进行被动转移，或注射匙孔血蓝蛋白或纯化的IgG（而非PBS或右旋糖酐），也会导致TG的慢性感染。
