Multi-layered Gag-specific immunodominant responses contribute to improved viral control in the CRF01_AE subtype of HIV-1-infected MSM subjects
Multi-layered Gag-specific immunodominant responses contribute to improved viral control in the CRF01_AE subtype of HIV-1-infected MSM subjects
复制标题
多层 Gag 特异性免疫显性反应有助于改善 HIV-1 感染 MSM 受试者 CRF01_AE 亚型的病毒控制
DOI：
10.1186/s12865-016-0166-8
复制
发表时间：
2016-08-30
期刊：
影响因子：
3
通讯作者：
Shang, Hong
中科院分区：
文献类型：
--
作者：
Jiang, Fanming;Han, Xiaoxu;Shang, Hong
BackgroundThe目的是本研究的特点特异性细胞毒性T细胞（CTL）的反应在男性与男性发生性关系（MSM）受试者感染的人类免疫缺陷病毒1型（HIV-1）CRF01_AE亚型在感染的第一年和对病毒的控制和evolution.Results15 HIV-1原发性感染者从辽宁MSM前瞻性队列招募。用γ干扰素酶联免疫斑点法（ELISPOT）检测感染后3个月和1年时对Gag、Pol和Nef蛋白的CTL应答，该方法使用优化的共有重叠肽以及来自同步血浆的病毒准种序列。Gag和Nef蛋白是HIV-1感染第一年期间CTL应答的主要靶标，这从通过除以相应蛋白的氨基酸数并乘以100调整氨基酸长度后的数据中显而易见。此外，感染后3个月和1年的Gag相对幅度与病毒设定点显著负相关（p= 0.002，r =-0.726;p= 0.025，r =-0.574）。而感染后1年Nef的相对值与病毒设定点呈显著正相关（p= 0.004，r = 0.697）。受试者在感染的第一年与多层Gag免疫显性反应有显着降低的病毒设定点比没有这样的反应的受试者（p= 0.002）。结论多层Gag免疫显性反应在感染的第一年与病毒控制，这为针对MSM受试者的疫苗设计与CRF01_AE亚型提供了理论依据。
BackgroundThe purpose of this study was to characterize specific cytotoxic T-cell (CTL) responses in men who have sex with men (MSM) subjects infected with the human immunodeficiency virus type 1 (HIV-1) CRF01_AE subtype during the first year of infection and impacts on viral control and evolution.ResultsFifteen HIV-1 primary infected cases were recruited from Liaoning MSM prospective cohort. CTL responses to Gag, Pol and Nef proteins at 3 month and 1 year post infection were detected with Gamma interferon enzyme-linked immunospot (ELISPOT) assay using optimized consensus overlapping peptides, as well as the viral quasispecies sequences from the synchronous plasma. Gag and Nef proteins were the main targets of CTL responses during the first year of HIV-1 infection, and this was evident from the data after adjusting for the length of amino acids by dividing the amino acids number of the corresponding protein and multiplying by 100. Additionally, relative magnitudes of Gag at both 3 months and 1 year post infection were significantly negatively correlated with the viral set point (p= 0.002,r= −0.726;p= 0.025,r= −0.574). While the relative magnitude of Nef at 1 year post infection were significantly positively correlated with viral set point (p= 0.004,r= 0.697). Subjects with multi-layered Gag immunodominant responses during the first year of infection had significantly lower viral set points than subjects without such responses (p= 0.002).ConclusionMulti-layered Gag immunodominant responses during the first year of infection were correlated with viral control, which provides a theoretical basis for vaccine design targeting MSM subjects with the CRF01_AE subtype.