Trivedi P, Meyer K K, Streblow D N, Preuninger B L, Schultz K T, Pauza C D
Department of Pathology and Laboratory Medicine, University of Wisconsin, Madison 53706-1532.
J Virol. 1994 Nov;68(11):7649-53. doi: 10.1128/JVI.68.11.7649-7653.1994.
Animal models for sexual transmission of human immunodeficiency virus can define the influences of virus type, dose, and route of inoculation on infection and clinical outcome. We used an uncloned simian immunodeficiency virus stock (SIVmac) to inoculate cells in vitro and to inoculate rhesus monkeys by intravenous and intrarectal routes. The distribution of virus genotypes present in each of these infection examples was characterized by DNA sequence analysis of viral long terminal repeats (LTRs). Our analysis of LTR sequences from in vitro and in vivo infections revealed three main genotypes: one genotype was observed only for in vitro infection, and two other genotypes were recovered only from infected animals. By comparing animals inoculated with high intrarectal doses of SIVmac and those inoculated with low doses, we demonstrated that unique subsets of the stock were selected after intrarectal infection. Our findings indicate that minor genotypes present in the stock cross the rectal mucosa and are amplified selectively to become prominent in peripheral blood mononuclear cells from acutely infected animals. Studies with a molecular recombinant of SIV and human immunodeficiency virus type 1 sequences, SHIV, showed that viral LTR sequences do not undergo especially rapid sequence variation or rearrangement after intrarectal inoculation. The mucosal barrier exerts a significant influence on infection and disease progression by reducing the efficiency of SIVmac infection and by permitting distinct, pathogenic genotypes to become established in the host.
人类免疫缺陷病毒性传播的动物模型可以确定病毒类型、剂量和接种途径对感染及临床结果的影响。我们使用未克隆的猿猴免疫缺陷病毒毒株（SIVmac）在体外接种细胞，并通过静脉内和直肠内途径接种恒河猴。通过对病毒长末端重复序列（LTRs）进行DNA序列分析，对这些感染实例中存在的病毒基因型分布进行了表征。我们对体外和体内感染的LTR序列分析揭示了三种主要基因型：一种基因型仅在体外感染中观察到，另外两种基因型仅从受感染动物中分离得到。通过比较直肠内高剂量接种SIVmac的动物和低剂量接种的动物，我们证明直肠内感染后毒株中独特的亚群被选择。我们的研究结果表明，毒株中存在的次要基因型穿过直肠黏膜并被选择性扩增，从而在急性感染动物的外周血单核细胞中变得突出。对SIV与1型人类免疫缺陷病毒序列的分子重组体SHIV的研究表明，直肠内接种后病毒LTR序列不会发生特别快速的序列变异或重排。黏膜屏障通过降低SIVmac感染的效率以及允许不同的致病基因型在宿主体内确立，对感染和疾病进展产生重大影响。
