ADAPTATION TO PERSISTENT GROWTH IN THE H9 CELL-LINE RENDERS A PRIMARY ISOLATE OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 SENSITIVE TO NEUTRALIZATION BY VACCINE SERA
ADAPTATION TO PERSISTENT GROWTH IN THE H9 CELL-LINE RENDERS A PRIMARY ISOLATE OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 SENSITIVE TO NEUTRALIZATION BY VACCINE SERA
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DOI：
10.1128/jvi.69.1.39-48.1995
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发表时间：
1995-01-01
影响因子：
5.4
通讯作者：
NUNBERG, JH
中科院分区：
文献类型：
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作者：
WRIN, T;LOH, TP;NUNBERG, JH
对7株不同的HIV-1原代分离株进行了检测，发现其不能被HIV-1 MN的重组gp 120（rgp 120）蛋白抗血清中和。这与某些实验室适应性病毒所表现出的敏感性形成鲜明对比。为了了解原代病毒和实验室适应病毒之间的差异，我们使原代病毒ACH 168.10适应在FDA/H9细胞系中生长。选择ACH 168.10是因为gp 120的V3区与MN的V3区紧密匹配。4周后，感染变得明显。病毒（168 A）在FDA/H9细胞中复制，具有广泛的细胞病变效应，但对抗体介导的中和的敏感性不变。因此，细胞系中的生长不足以使原代病毒对中和敏感。但168 A病毒对CD 4免疫粘附素（CD 4-IG）部分敏感。继续适应以产生持续感染的FDA/H9培养物，其显示最小的细胞病变效应。该病毒（168 C）现在对MN rgp 120疫苗血清和MN特异性单克隆抗体的中和敏感，并显示对HIVIG和CD 4-IG的敏感性增加。168 C编码gp 120中的三个氨基酸变化，包括V3环内的一个（I-166-->R，I-282-->N，G-318-->R）。MN特异性单克隆抗体同样结合到感染有中和抗性或敏感性病毒的细胞表面。中和敏感性变化与细胞嗜性和细胞病变效应变化的一致性表明了通过整个包膜蛋白复合物起作用的共同潜在机制。
Seven diverse primary isolates of human immunodeficiency virus type 1 (HIV-1) mere examined and found to be refractory to neutralization by antisera to recombinant gp120 (rgp120) protein from HIV-1 MN. This stands in marked contrast to the sensitivity exhibited by certain laboratory-adapted viruses. To understand the difference between primary and laboratory-adapted viruses, we adapted the primary virus ACH 168.10 to growth in the FDA/H9 cell line. ACH 168.10 was chosen because the V3 region of gp120 closely matches that of MN. After 4 weeks, infection became evident. The virus (168A) replicated in FDA/H9 cells with extensive cytopathic effect but was unchanged in sensitivity to antibody-mediated neutralization. Thus, growth in cell lines is not sufficient to render primary virus sensitive to neutralization. The 168A virus was, however, partially sensitive to CD4 immunoadhesin (CD4-Ig). Adaptation was continued to produce a persistently infected FDA/H9 culture that displayed minimal cytopathic effect. The virus (168C) was now sensitive to neutralization by MN rgp120 vaccine sera and by MN-specific monoclonal antibodies and showed increased sensitivity to HIVIG and CD4-Ig. 168C encoded three amino acid changes in gp120), including one within the V3 loop (I-166-->R, I-282-->N, G-318-->R). MN-specific monoclonal antibodies bound equally lo the surface of cells infected with either neutralization-resistant or -sensitive virus. The coincidence of changes in neutralization sensitivity with changes in cell tropism and cytopathic effect suggests a common underlying mechanism(s) acting through the whole of the envelope protein complex.