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首页> 外文期刊>AIDS Research and Human Retroviruses >Neutralization Patterns and Evolution of Sequential HIV Type 1 Envelope Sequences in HIV Type 1 Subtype B-Infected Drug-Naive Individuals
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Neutralization Patterns and Evolution of Sequential HIV Type 1 Envelope Sequences in HIV Type 1 Subtype B-Infected Drug-Naive Individuals

机译：HIV 1型亚型B感染过的单纯药物治疗个体中HIV 1型连续信封序列的中和模式和进化

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To design a vaccine that will remain potent against HIV-1, the immunogenic regions in the viral envelope that tend to change as well as those that remain constant over time must be identified. To determine the neutralization profiles of sequential viruses over time and study whether neutralization patterns correlate with sequence evolution, 12 broadly neutralizing plasmas from HIV-1 subtype B-infected individuals were tested for their ability to neutralize sequential primary HIV-1 subtype B viruses from four individuals. Three patterns of neutralization were observed, including a loss of neutralization sensitivity by viruses over time, an increase in neutralization sensitivity by sequential viruses, or a similarity in the sensitivity of sequential viruses to neutralization. Seven to 11 gp160 clones from each sequential virus sample were sequenced and analyzed to identify mutational patterns. Analysis of the envelope sequences of the sequential viruses revealed changes characteristic of the neutralization patterns. Viruses that evolved to become resistant to neutralizing antibodies also evolved with diverse sequences, with most of the changes being due to nonsynonymous mutations occurring in the V1/V2, as well as in the constant regions (C2, C3, C4), the most changes occurring in the C3. Viruses from the patient that evolved to become more sensitive to neutralization exhibited less sequence diversity with fewer nonsynonymous changes that occurred mainly in the V1/V2 region. The V3 region remained constant over time for all the viruses tested. This study demonstrates that as viruses evolve in their host, they either become sensitive or resistant to neutralization by antibodies in heterologous plasma and mutations in different envelope regions account for these changes in their neutralization profiles
机译：为了设计对HIV-1仍然有效的疫苗，必须确定病毒包膜中易于改变的免疫原性区域以及随时间推移保持不变的免疫原性区域。为了确定连续病毒随时间的中和谱并研究中和模式是否与序列进化相关，测试了来自HIV-1亚型B感染个体的12种广泛中和血浆的中和能力。个人。观察到三种中和模式，包括病毒随着时间的推移中和敏感性的下降，连续病毒对中和敏感性的增加或连续病毒对中和敏感性的相似性。对来自每个连续病毒样品的7至11个gp160克隆进行测序和分析，以鉴定突变模式。对顺序病毒的包膜序列的分析揭示了中和模式的变化特征。进化为对中和抗体具有抗性的病毒也进化出多种序列，其中大部分变化是由于V1 / V2以及恒定区（C2，C3，C4）中发生的非同义突变所致发生在C3中来自患者的对中和变得更加敏感的病毒表现出较少的序列多样性，较少的非同义变化主要发生在V1 / V2区域。对于所有测试的病毒，V3区域随时间保持不变。这项研究表明，随着病毒在宿主中的进化，它们变得对异源血浆中的抗体敏感或对中和具有抗性，并且不同包膜区域的突变解释了它们中和谱的这些变化

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