Contrasting antibody responses to intrasubtype superinfection with CRF02_AG.
Contrasting antibody responses to intrasubtype superinfection with CRF02_AG.
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DOI：
10.1371/journal.pone.0173705
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发表时间：
2017
期刊：
影响因子：
3.7
通讯作者：
Dürr R
中科院分区：
文献类型：
--
作者：
Courtney CR;Mayr L;Nanfack AJ;Banin AN;Tuen M;Pan R;Jiang X;Kong XP;Kirkpatrick AR;Bruno D;Martens CA;Sykora L;Porcella SF;Redd AD;Quinn TC;Nyambi PN;Dürr R
HIV重叠感染是指一个人连续感染两种或两种以上不相关的HIV病毒株。亚型间重叠感染已被证明会导致更广泛和更有效的异源中和抗体反应相比，单一感染的控制，但亚型内重叠感染的影响仍然存在争议。使用下一代测序和包膜克隆对纵向样品的pol和env区域进行遗传学分析。评估了CRF02_AG亚型内重复感染对异源中和和抗体结合应答的影响。我们比较了两例CRF02_AG亚型内重复感染，发现通过重复感染具有重组迹象的CRF02_AG变异体完全替代了初始病毒。在较早时间点成为超感染的NYU 6564与NYU 6501相比，在超感染后表现出更大的抗体结合谱变化，并产生更有效的中和抗体应答。相比之下，在NYU 6501中，重复感染发生在较晚的时间点，其中菌株具有显著更长的V1 V2区域，中和模式没有观察到变化。在这里，我们表明，CRF02_AG intrasubtype重叠感染可以诱导交叉亚型中和抗体反应，我们的数据表明，时间和/或重叠感染的病毒包膜特征作为影响因素。这些结果突出了亚型内重叠感染的不同结局，并首次深入了解了CRF02_AG病例，CRF02_AG是全球第四大流行的HIV-1毒株。
HIV superinfection describes the sequential infection of an individual with two or more unrelated HIV strains. Intersubtype superinfection has been shown to cause a broader and more potent heterologous neutralizing antibody response when compared to singly infected controls, yet the effects of intrasubtype superinfection remain controversial. Longitudinal samples were analyzed phylogenetically for pol and env regions using Next-Generation Sequencing and envelope cloning. The impact of CRF02_AG intrasubtype superinfection was assessed for heterologous neutralization and antibody binding responses. We compared two cases of CRF02_AG intrasubtype superinfection that revealed complete replacement of the initial virus by superinfecting CRF02_AG variants with signs of recombination. NYU6564, who became superinfected at an early time point, exhibited greater changes in antibody binding profiles and generated a more potent neutralizing antibody response post-superinfection compared to NYU6501. In contrast, superinfection occurred at a later time point in NYU6501 with strains harboring significantly longer V1V2 regions with no observable changes in neutralization patterns. Here we show that CRF02_AG intrasubtype superinfection can induce a cross-subtype neutralizing antibody response, and our data suggest timing and/or superinfecting viral envelope characteristics as contributing factors. These results highlight differential outcomes in intrasubtype superinfection and provide the first insight into cases with CRF02_AG, the fourth most prevalent HIV-1 strain worldwide.