Klein R J, Friedman-Kien A E, DeStefano E
Infect Immun. 1981 Dec;34(3):693-701. doi: 10.1128/iai.34.3.693-701.1981.
The comparative analysis of the pathogenicity of a parental herpes simplex virus type 1 strain and its phosphonoacetic acid (PAA)-resistant and acyclovir (ACV)-resistant mutants showed marked differences among them. After orofacial skin inoculation of hairless mice the parental and PAA-resistant viruses were detected during the first 4 days after infection at high and increasing titers in the trigeminal ganglia; the ACV-resistant mutant was present at low and decreasing titers in the ganglia. Severe and slow-healing skin lesions were produced by the parental and PAA-resistant viruses; mild and rapidly healing lesions were produced by the ACV-resistant mutant. Virus titers in ganglia and the intensity of skin lesions were related to the virus dose used in the primary infection. Latent infections became established in trigeminal ganglia of mice inoculated with 10(6.0) plaque-forming units of the parental or PAA-resistant virus; no latent infections were detected in ganglia of mice inoculated with 10(7.0) plaque-forming units of the ACV-resistant mutant. Serum antibody titers attained similar values 4 weeks after primary infection with both mutants and the parental virus. Mice infected with the ACV-resistant mutant were reinfected with the parental and PAA-resistant viruses; the degree of protection against development of skin lesions, mortality, and latency was related to the dose of ACV-resistant virus used in the primary infection. Mortality was prevented by a dose of 10(6.0) plaque-forming units, skin lesions were prevented by a dose of 10(6.5) plaque-forming units, and latency was prevented by a dose of 10(7.0) plaque-forming units of the ACV-resistant mutant. Protection against reinfection with the PAA-resistant mutant was achieved with lower doses than protection against the parental virus. Serum antibody titers showed a 4- to 15-fold increase after reinfection. The results suggest that the ACV-resistant, latency-negative mutant has many attributes of a live attenuated herpes simplex virus vaccine.
对单纯疱疹病毒1型亲本毒株及其膦甲酸（PAA）抗性和阿昔洛韦（ACV）抗性突变株的致病性进行比较分析，结果显示它们之间存在显著差异。在无毛小鼠经口面部皮肤接种后，亲本病毒和PAA抗性病毒在感染后的前4天内在三叉神经节中被检测到，滴度高且不断上升；ACV抗性突变株在神经节中的滴度低且不断下降。亲本病毒和PAA抗性病毒产生严重且愈合缓慢的皮肤病变；ACV抗性突变株产生轻微且愈合迅速的病变。神经节中的病毒滴度和皮肤病变的严重程度与初次感染时使用的病毒剂量有关。接种10(6.0) 个空斑形成单位的亲本或PAA抗性病毒的小鼠三叉神经节中建立了潜伏感染；接种10(7.0) 个空斑形成单位的ACV抗性突变株的小鼠神经节中未检测到潜伏感染。两种突变株和亲本病毒初次感染4周后血清抗体滴度达到相似值。感染ACV抗性突变株的小鼠再次感染亲本病毒和PAA抗性病毒；对皮肤病变发展、死亡率和潜伏感染的保护程度与初次感染时使用的ACV抗性病毒剂量有关。10(6.0) 个空斑形成单位的剂量可预防死亡率，10(6.5) 个空斑形成单位的剂量可预防皮肤病变，10(7.0) 个空斑形成单位的ACV抗性突变株剂量可预防潜伏感染。预防再次感染PAA抗性突变株所需的剂量低于预防亲本病毒所需的剂量。再次感染后血清抗体滴度增加了4至15倍。结果表明，ACV抗性、潜伏阴性突变株具有减毒活单纯疱疹病毒疫苗的许多特性。
