EMERGENCE OF VIRUSES RESISTANT TO NEUTRALIZATION BY V3-SPECIFIC ANTIBODIES IN EXPERIMENTAL HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1-IIIB INFECTION OF CHIMPANZEES
EMERGENCE OF VIRUSES RESISTANT TO NEUTRALIZATION BY V3-SPECIFIC ANTIBODIES IN EXPERIMENTAL HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1-IIIB INFECTION OF CHIMPANZEES
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DOI：
10.1128/jvi.64.8.3779-3791.1990
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发表时间：
1990-08-01
影响因子：
5.4
通讯作者：
GOUDSMIT, J
中科院分区：
文献类型：
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作者：
NARA, PL;SMIT, L;GOUDSMIT, J
出现在两个黑猩猩的人类免疫缺陷病毒1型（HIV-1）IIIB变种耐中和预先存在的抗体。从HIV-1 IIIB gp 120免疫和攻击动物分离的病毒比从幼稚感染动物分离的病毒对黑猩猩自身血清的中和更具抗性，表明免疫压力是选择性机制。然而，所有再分离的病毒比接种病毒对结合HIV-1外包膜第三可变结构域（V3）的抗体的中和抗性高16至256倍。早期黑猩猩血清样品，中和接种株，但不是重新分离的病毒被发现结合HIV-1 IIIB常见的九肽（IQRGPGRAF）来自gp 120分离特异性V3域显示诱导分离特异性中和在其他动物。通过聚合酶链反应扩增V3编码序列，随后对从体内感染的动物获得的中和抗性变体进行序列分析，表明对HIV-1 IIIB单克隆抗体（0.5 β）中和的早期抗性。由选择性中和抗体的直接结合位点以外的变化赋予。经生物学和序列分析证实，重新分离的耐中和分离株由HIV-1 IIIB贮备液的低复制能力病毒亚群组成。在体外通过黑猩猩和人类外周血单核细胞培养的HIV-1 IIIB股票无效的HIV特异性抗体导致在原始病毒股票中预先存在的更复制能力的亚群的同源扩增，这表明免疫系统在抑制更多的复制能力的病毒的作用。
Emergence in two chimpanzees of human immunodeficiency virus type 1 (HIV-1) IIIB variants resistant to neutralization by the preexisting antibody is described. Viruses isolated from the HIV-1 IIIB gp 120-vaccinated and -challenged animal were more resistant to neutralization by the chimpanzee''s own serum than viruses isolated from the naive infected animal, indicating immune pressure as the selective mechanism. However, all reisolated viruses were 16- to 256-fold more neutralization resistant than the inoculum virus to antibodies binding to the third variable domain (V3) of the HIV-1 external envelope. Early chimpanzee serum samples that neutralized the inoculum strain but not the reisolated viruses were found to bind an HIV-1 IIIB common nonapeptide (IQRGPGRAF) derived from the gp120 isolate-specific V3 domain shown to induce isolate-specific neutralization in other animals. Amplification of the V3 coding sequence by polymerase chain reaction and subsequent sequence analysis of the neutralization-resistant variants obtained from in vivo-infected animals indicated that early resistance to neutralization by an HIV-1 IIIB monoclonal antibody (0.5 .beta.) was conferred by changes outside the direct binding site for the selective neutralizing antibody. The reisolated neutralization-resistant isolates consisted of the lower-replication-competent virus subpopulation of the HIV-1 IIIB stock, as confirmed by biological and sequence analyses. In vitro passage of the HIV-1 IIIB stock through chimpanzee and human peripheral blood mononuclear cell cultures void of HIV-specific antibody resulted in homogenic amplification of the more-replication-competent subpopulation preexisting in the original viral stock, suggesting a role for the immune system in suppressig the more-replication-competent viruses.