Prevalence of cross-reactive HIV-1-neutralizing activity in HIV-1-infected patients with rapid or slow disease progression
Prevalence of cross-reactive HIV-1-neutralizing activity in HIV-1-infected patients with rapid or slow disease progression
复制标题
DOI：
10.1097/qad.0b013e32833243e7
复制
发表时间：
2009-11-27
期刊：
影响因子：
3.8
通讯作者：
Schuitemaker, Hanneke
中科院分区：
文献类型：
--
作者：
van Gils, Marit J.;Euler, Zelda;Schuitemaker, Hanneke
目的：HIV-1的天然包膜gp 160三聚体被认为可以屏蔽脆弱的表位，否则这些表位可能会引发有效的中和抗体。然而，鲜为人知的是，自然发生的广泛中和活性在血清中的HIV-1-infected individual.Methods：在这里，我们研究了35名参与者的阿姆斯特丹队列研究HIV-1感染（20个长期nonprogressors和15个progressors）的交叉反应中和活性在他们的血清中的存在下，在2年和4年后血清转换。中和活性进行了测试，在假病毒检测，对一个小组的HIV-1包膜变异亚型A，13，C和D.结果：已经在第2年血清转换后，7个35人（20%）有交叉反应中和活性，增加到11个人（31%）在4年后血清转换。在长期无进展者和进展者之间，交叉反应性中和血清活性的患病率没有差异。有趣的是，在设定点时，高血浆病毒RNA载量和低CD 4（+）细胞计数与交叉反应性中和活性的早期发展相关。血清中的中和滴度在感染过程中增加91%的个人在这里研究，虽然不太迅速为那些谁没有开发交叉反应中和activity.Conclusion：总体而言，我们在这里证明了一个相对较高的患病率的交叉反应中和血清活性在HIV-1感染的患者，这增加了感染的持续时间。这些数据可能意味着HIV-1的天然包膜刺突的免疫原性引起交叉反应性体液免疫应答可能比以前预期的更好。(C)2009年威科健康|利平科特威廉姆斯&威尔金斯
Objective: The native envelope gp160 trimer of HIV-1 is thought to shield vulnerable epitopes that could otherwise elicit effectively neutralizing antibodies. However, little is known about the prevalence of naturally occurring broadly neutralizing activity in serum of HIV-1-infected individuals.Methods: Here, we studied 35 participants of the Amsterdam Cohort Studies on HIV-1 infection (20 long-term nonprogressors and 15 progressors) for the presence of cross-reactive neutralizing activity in their sera at 2 and 4 years after seroconversion. Neutralizing activity was tested in a pseudovirus assay, against a panel of HIV-1 envelope variants from subtypes A, 13, C, and D.Results: Already at year 2 after seroconversion, seven out of 35 individuals (20%) had cross-reactive neutralizing activity, which increased to 11 individuals (31%) at 4 years after seroconversion. There was no difference in the prevalence of cross-reactive neutralizing serum activity between long-term nonprogressors and progressors. Interestingly, high plasma viral RNA load and low CD4(+) cell count at set-point were associated with early development of cross-reactive neutralizing activity. Neutralization titers in serum increased during the course of infection for 91% of individuals studied here, although less rapidly for those who did not develop cross-reactive neutralizing activity.Conclusion: Overall, we here demonstrate a relatively high prevalence of cross-reactive neutralizing serum activity in HIV-1-infected patients, which increased with duration of infection. These data may imply that immunogenicity of the native envelope spike of HIV-1 for eliciting cross-reactive humoral immune responses may be better than previously anticipated. (C) 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins