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Envelope characteristics in individuals who developed neutralizing antibodies targeting different epitopes in HIV-1 subtype C infection.
Virology ( IF 2.8 ) Pub Date : 2020-03-25 , DOI: 10.1016/j.virol.2020.03.003
Bongiwe Ndlovu 1 , Kamini Gounder 2 , Daniel Muema 3 , Nagarajan Raju 4 , Tandile Hermanus 5 , Qiniso Mthethwa 1 , Kim Robertson 1 , Bruce D Walker 6 , Ivelin S Georgiev 4 , Lynn Morris 7 , Penny L Moore 7 , Thumbi Ndung'u 8
Affiliation  

Broadly neutralizing antibodies (bNAbs) may constitute an essential component of a protective vaccine against HIV-1, yet no immunogen has been able to elicit them. To characterize the development of bNAbs in HIV-1 subtype C infected individuals, a panel of 18 Env-pseudotyped viruses was used to screen 18 study participants. The specificity of plasma neutralization was mapped against Env mutants and MPER chimeras. Envelope (env) gene sequence evolution was characterized by single genome amplification and sequencing. Three out of eighteen individuals developed broad plasma neutralizing activity (>60% breadth). Two of the three participants may target epitopes comprising glycans at position 276 of the D loop in the CD4 binding site and 332 glycan supersite, respectively. Deletion of these glycans was associated with neutralization resistance. Our study describes the kinetics of the development of plasma neutralizing activity and identified amino acid residue changes suggestive of immune pressure on putative epitopes. The study enhances our understanding of how neutralization breadth develops in the course of HIV-1 subtype C infection.

中文翻译:

在针对HIV-1 C亚型感染的不同表位的中和抗体中产生个体的信封特征。

广泛中和的抗体(bNAb)可能构成针对HIV-1的保护性疫苗的重要组成部分,但尚无免疫原能够引发它们。为了表征在HIV-1亚型C感染个体中bNAb的发育,使用18种Env假型病毒组成的小组筛选了18名研究参与者。血浆中和的特异性针对Env突变体和MPER嵌合体。信封(env)基因序列的进化是通过单基因组扩增和测序来表征的。18个人中有3个人具有广泛的血浆中和活性(广度> 60%)。三个参与者中的两个可以分别靶向在CD4结合位点的D环的276位和332个聚糖超位点包含聚糖的表位。这些聚糖的缺失与中和抗性有关。我们的研究描述了血浆中和活性的发展动力学,并鉴定了氨基酸残基变化,提示对假定表位的免疫压力。这项研究增强了我们对HIV-1 C型亚型感染过程中中和广度如何发展的理解。
更新日期:2020-03-25
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