Lemon S M, Chao S F, Jansen R W, Binn L N, LeDuc J W
J Virol. 1987 Mar;61(3):735-42. doi: 10.1128/JVI.61.3.735-742.1987.
Cloned cDNA probes derived from the P1 and P2 regions of the genome of HM175 virus, a reference strain of human hepatitis A virus (HAV), failed to hybridize under standard stringency criteria with RNA from PA21 and PA33 viruses, two epizootiologically related HAV strains recovered from naturally infected New World owl monkeys. Hybridization of these probes to PA21 RNA was only evident under reduced stringency conditions. However, cDNA representing the 5' nontranslated region of the HM175 genome hybridized equally to HM175 and PA21 RNA under standard stringency conditions, while a probe derived from the 3' 1,400 bases of the genome yielded a reduced hybridization signal with PA21 RNA. In contrast, no differences could be discerned between HM175 virus and three other HAV strains of human origin (GR8, LV374, and MS1) in any region of the genome, unless increased stringency conditions were used. These results suggest that PA21 and PA33 are unique among HAV isolates and may represent a virus native to the owl monkey. Despite extremely poor homology within the P1 region, which encodes capsid polypeptides, monoclonal antibody analysis confirmed that the immunodominant neutralization epitopes of HAV were highly conserved between HM175 and PA21 viruses. Furthermore, experimental challenge of the owl monkey with successive PA33 and HM175 inocula confirmed a high but incomplete degree of cross-protection. Only one of six monkeys previously infected with PA33 developed recurrent hepatitis 28 days after intravenous HM175 challenge, while none of six monkeys previously infected with HM175 had demonstrable hepatitis following PA33 challenge. These data provide molecular evidence for the existence of HAV strains unique to nonhuman primate species and indicate that strict conservation of antigenic function may accompany substantial genetic divergence in HAV.
源自人甲型肝炎病毒（HAV）参考毒株HM175病毒基因组P1和P2区域的克隆cDNA探针，在标准严谨性条件下未能与从自然感染的新大陆猫头鹰猴中分离出的两种流行病学相关的HAV毒株PA21和PA33病毒的RNA杂交。只有在降低严谨性条件下，这些探针与PA21 RNA的杂交才明显。然而，代表HM175基因组5'非翻译区的cDNA在标准严谨性条件下与HM175和PA21 RNA的杂交程度相同，而源自基因组3'端1400个碱基的探针与PA21 RNA的杂交信号减弱。相比之下，除非使用更高的严谨性条件，否则在基因组的任何区域中，都无法区分HM175病毒与其他三种人类来源的HAV毒株（GR8、LV374和MS1）。这些结果表明，PA21和PA33在HAV分离株中是独特的，可能代表一种原产于猫头鹰猴的病毒。尽管在编码衣壳多肽的P1区域内同源性极低，但单克隆抗体分析证实，HAV的免疫显性中和表位在HM175和PA21病毒之间高度保守。此外，用连续的PA33和HM175接种物对猫头鹰猴进行实验性攻击，证实了高度但不完全的交叉保护。在静脉注射HM175攻击28天后，先前感染PA33的六只猴子中只有一只出现复发性肝炎，而先前感染HM175的六只猴子在接受PA33攻击后均未出现可检测到的肝炎。这些数据为非人类灵长类物种特有的HAV毒株的存在提供了分子证据，并表明在HAV中，抗原功能的严格保守可能伴随着大量的基因分歧。
