The existence of an antisense Open Reading Frame (ORF) that encodes a putative AntiSense Protein (ASP) on the proviral genome of Human Immunodeficiency Virus type 1 (HIV-1) was a source of debate for 30 years. During the last years, some progresses have been made to characterize the cellular immune response against ASP in HIV-1 seropositive patients. However, no tools were available for the detection of antibodies to ASP in the plasma of HIV-1-infected patients during the natural course of the infection. The aim of our study was to develop a Luciferase Immuno-Precipitation System (LIPS) to monitor the quantitative detection of ASP-specific antibodies in the plasma of HIV-1-infected patients [antiretroviral therapy (ART) naive-patients, patients under ART and HIV-1 controllers], patients who discontinued antiretroviral drugs (ARV). We further used this approach to delineate the epitopes of ASP targeted by antibodies. Antibodies directed against ASP were detected in 3 out of 19 patients who discontinued ARV (15%) and in 1 out of 10 ART-naive patients (10%), but were neither detected in HIV-1 infected patients under ART nor in HIV-1 controllers. Individual variations in levels of ASP-specific antibodies were detected overtime. Both the conserved prolin-rich motif and the core 60-189 region of ASP were found to be essential for antibody recognition in the four patients tested positive for anti-ASP antibodies, who were all untreated at the time of sampling. Moreover, for two of these patients, increased levels of ASP-specific antibodies were observed concomitantly to viremia declines. Overall, our method may represent a useful tool to detect a humoral response to ASP in HIV-1-infected patients, which allowed us to confirm the expression of ASP during the course of HIV-1 infection. Further studies will be needed to fully characterize the humoral response to ASP in HIV-1-infected patients.

中文翻译：

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在HIV-1感染患者中针对抗感蛋白（ASP）的体液反应的初步研究。

在人类免疫缺陷病毒1型（HIV-1）的原病毒基因组上编码一个假定的反义蛋白（ASP）的反义开放阅读框（ORF）的存在是30年以来的争论之源。在最近几年中，在表征HIV-1血清反应阳性患者中针对ASP的细胞免疫反应方面取得了一些进展。但是，没有工具可用于在自然感染过程中检测HIV-1感染患者血浆中的ASP抗体。我们研究的目的是开发一种荧光素酶免疫沉淀系统（LIPS），以监测HIV-1感染患者血浆中ASP特异性抗体的定量检测[抗逆转录病毒疗法（ART）天真的患者，接受ART的患者和HIV-1控制者]，停用抗逆转录病毒药物（ARV）的患者。我们进一步使用这种方法来描述抗体靶向的ASP的表位。在终止ARV的19例患者中，有3例（15％）检出了针对ASP的抗体，而在未进行过ART的10例患者中，有1例（10％）检出了抗ASP抗体，但在接受ART的HIV-1感染患者和HIV 1个控制器。随着时间的推移检测到ASP特异性抗体水平的个体差异。在被测试为抗ASP抗体阳性的四名患者中，均发现了保守的富含脯氨酸的基序和ASP的核心60-189区域对于抗体识别都是必不可少的，这些患者在采样时均未接受治疗。此外，对于其中的两名患者，伴随病毒血症下降，观察到ASP特异性抗体水平升高。总体，我们的方法可能是检测HIV-1感染患者对ASP的体液反应的有用工具，这使我们能够确定HIV-1感染过程中ASP的表达。需要进一步研究以充分表征HIV-1感染患者对ASP的体液反应。