Djordjevic Ana, Veljkovic Milena, Antoni Sascha, Sakarellos-Daitsiotis Maria, Krikorian Dimitrios, Zevgiti Stella, Dietrich Ursula, Veljkovic Nevena, Branch Donald R
Centre for Multidisciplinary Research, Institute of Nuclear Sciences VINCA, Belgrade, Serbia.
Curr HIV Res. 2007 Sep;5(5):443-8. doi: 10.2174/157016207781662470.
The C-terminus of the second conserved region of HIV-1 gp120 represents a functionally important domain, as it encompasses amino acids directly involved in the binding to the CD4 receptor and in post-receptor binding events. Previous studies have suggested that antibodies with specific affinity to a 23 amino acids-long NTM polypeptide, derived from this HIV-1 gp120 domain, may be involved in the control of HIV disease progression. In the current work, we searched for NTM-recognizing antibodies in specific cohorts of HIV-1 infected individuals, including long-term nonprogressors (LTNP) and progressors. For this purpose, we employed a previously defined bioinformatics criterion for design of an NTM peptide mimetic to select an octapeptide, NTMs (FTDNAKTI), which is more suitable for use in a solid-state enzyme-linked immunosorbent assay (ELISA). Our results show that NTMs-reactive antibodies are significantly more prevalent (p < 0.01) in LTNP as compared to progressors and healthy control subjects, indicating their association with non-progressive infection. The presence of antibodies recognizing the second conserved region of the HIV-1 gp120 derived peptide, NTMs, in LTNP sera suggest that these antibodies could be of considerable interest for development of anti-HIV immune-based therapies and vaccines.
HIV-1 gp120第二个保守区域的C末端代表一个功能上重要的结构域,因为它包含直接参与与CD4受体结合以及受体后结合事件的氨基酸。先前的研究表明,对源自该HIV-1 gp120结构域的一段23个氨基酸长的NTM多肽具有特异性亲和力的抗体,可能参与了HIV疾病进展的控制。在当前的研究中,我们在HIV-1感染个体的特定队列中寻找识别NTM的抗体,包括长期不进展者(LTNP)和疾病进展者。为此,我们采用先前定义的用于设计NTM肽模拟物的生物信息学标准来选择一种八肽,即NTMs(FTDNAKTI),它更适合用于固态酶联免疫吸附测定(ELISA)。我们的结果表明,与疾病进展者和健康对照受试者相比,LTNP中识别NTMs的抗体显著更为普遍(p < 0.01),这表明它们与非进展性感染有关。LTNP血清中存在识别HIV-1 gp120衍生肽NTMs第二个保守区域的抗体,这表明这些抗体对于开发基于免疫的抗HIV疗法和疫苗可能具有相当大的意义。