HIV-1 subtype C superinfected individuals mount low autologous neutralizing antibody responses prior to intrasubtype superinfection.
HIV-1 subtype C superinfected individuals mount low autologous neutralizing antibody responses prior to intrasubtype superinfection.
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DOI：
10.1186/1742-4690-9-76
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发表时间：
2012-09-20
期刊：
影响因子：
3.3
通讯作者：
Hunter E
中科院分区：
文献类型：
--
作者：
Basu D;Kraft CS;Murphy MK;Campbell PJ;Yu T;Hraber PT;Irene C;Pinter A;Chomba E;Mulenga J;Kilembe W;Allen SA;Derdeyn CA;Hunter E
抗体在防止亚型内HIV-1重复感染中的潜在作用仍有待了解。我们比较了三名初次感染后一年内被重复感染的个体的早期中和抗体（NAb）反应，以及来自赞比亚C亚型传播病例队列的10名匹配的非重复感染对照。来自先前研究的单基因组扩增的全长envs序列分析显示，在血清转化后一年内成为同一HIV-1亚型重复感染的个体中，多样性有限。我们假设这反映了NAb反应的钝化，这可能使这些个体更容易受到重复感染。中和试验显示，在重复感染之前，所有三名重复感染者的自体血浆NAb对最早的病毒（在某些情况下是传播/始发病毒）的反应延迟，并且滴度低至无法检测。相比之下，在非超感染对照中，IC50滴度中位数为1896的nab早在血清转化后3个月就被检测到。所有受试者的早期血浆nab均显示有限但不同水平的异源中和广度。超感染个体也表现出gp120和v1v2特异性IgG结合抗体水平较低，而gp120特异性血浆IgA结合抗体水平较高的趋势。这些数据表明，在单一HIV-1亚型占主导地位的情况下，缺乏IgG抗体的发展，反映在自体抗体以及gp120和V1V2结合原发感染病毒的抗体中，结合潜在的竞争，非保护性IgA抗体，可能会增加对重复感染的易感性。
The potential role of antibodies in protection against intra-subtype HIV-1 superinfection remains to be understood. We compared the early neutralizing antibody (NAb) responses in three individuals, who were superinfected within one year of primary infection, to ten matched non-superinfected controls from a Zambian cohort of subtype C transmission cases. Sequence analysis of single genome amplified full-length envs from a previous study showed limited diversification in the individuals who became superinfected with the same HIV-1 subtype within year one post-seroconversion. We hypothesized that this reflected a blunted NAb response, which may have made these individuals more susceptible to superinfection. Neutralization assays showed that autologous plasma NAb responses to the earliest, and in some cases transmitted/founder, virus were delayed and had low to undetectable titers in all three superinfected individuals prior to superinfection. In contrast, NAbs with a median IC50 titer of 1896 were detected as early as three months post-seroconversion in non-superinfected controls. Early plasma NAbs in all subjects showed limited but variable levels of heterologous neutralization breadth. Superinfected individuals also exhibited a trend toward lower levels of gp120- and V1V2-specific IgG binding antibodies but higher gp120-specific plasma IgA binding antibodies. These data suggest that the lack of development of IgG antibodies, as reflected in autologous NAbs as well as gp120 and V1V2 binding antibodies to the primary infection virus, combined with potentially competing, non-protective IgA antibodies, may increase susceptibility to superinfection in the context of settings where a single HIV-1 subtype predominates.
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