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对一名急性感染期治疗诱导的1型艾滋病毒控制者及其未控制的伴侣的A1/D重组亚型全长基因组进行的全面表征。

Full-length characterization of A1/D intersubtype recombinant genomes from a therapy-induced HIV type 1 controller during acute infection and his noncontrolling partner.

作者信息

Fomsgaard Anders, Vinner Lasse, Therrien Dominic, Jørgensen Louise B, Nielsen Claus, Mathiesen Lars, Pedersen Court, Corbet Sylvie

机构信息

Department of Virology, Statens Serum Institut, DK-2300 Copenhagen, Denmark.

出版信息

AIDS Res Hum Retroviruses. 2008 Mar;24(3):463-72. doi: 10.1089/aid.2006.0294.

Abstract

To increase the understanding of mechanisms of HIV control we have genetically and immunologically characterized a full-length HIV-1 isolated from an acute infection in a rare case of undetectable viremia. The subject, a 43-year-old Danish white male (DK1), was diagnosed with acute HIV-1 infection after 1 year in Uganda. Following transient antiretroviral therapy DK1 maintained undetectable viral load for more than 10 years. His Ugandan wife (UG1) developed high viral load. HIV-1 sequences from both individuals were compared by bootscanning for recombination break points. Diversity plots and phylogenic trees were constructed and diversity and evolutionary distances were calculated. Intracellular IFN-gamma in CD8(+)CD3(+) T-lymphocyte reactions was investigated by intracellular flow cytometry (IC-FACS). Virus isolates from both patients were A1D intersubtype recombinants showing 98% sequence homology in shared regions. Four of seven crossover points were identical; however, the env gene from UG1 was subtype D, but A1 in DK1. Both viruses encoded proteins of the expected length and replicated equally well in vitro. DK1 and UG1 shared the HLA-A02 tissue type. HLA-A02-restricted CD8(+) T cell IFN-gamma IC-FACS response in DK1 was detected against only one (Pol(476)) of 23 conserved epitopes. Neutralizing antibodies were induced only to the homologous isolate. These results indicate an A1D intersubtype recombination or transmission of a minor variant. Transient early antiretroviral therapy may have induced full HIV-1 control in this individual mediated by a narrow specific cytotoxic T lymphocyte and neutralizing antibody response and/or other factors yet to be characterized.

摘要

为了增进对HIV控制机制的理解,我们对从一名罕见的病毒血症无法检测到的急性感染中分离出的全长HIV-1进行了基因和免疫学特征分析。该患者是一名43岁的丹麦白人男性(DK1),在乌干达生活1年后被诊断为急性HIV-1感染。经过短暂的抗逆转录病毒治疗,DK1的病毒载量在超过10年的时间里一直检测不到。他的乌干达妻子(UG1)病毒载量很高。通过bootscanning比较了两人的HIV-1序列以寻找重组断点。构建了多样性图和系统发育树,并计算了多样性和进化距离。通过细胞内流式细胞术(IC-FACS)研究了CD8(+)CD3(+) T淋巴细胞反应中的细胞内干扰素-γ。两名患者的病毒分离株均为A1D亚型间重组体,在共享区域显示出98%的序列同源性。七个交叉点中的四个是相同的;然而,UG1的env基因是D亚型,而DK1的是A1亚型。两种病毒编码的蛋白质长度均符合预期,且在体外复制情况相同。DK1和UG1共享HLA-A02组织类型。在DK1中,针对23个保守表位中的仅一个(Pol(476))检测到了HLA-A02限制性CD8(+) T细胞干扰素-γ IC-FACS反应。仅对同源分离株诱导出了中和抗体。这些结果表明存在A1D亚型间重组或一个小变异体的传播。短暂的早期抗逆转录病毒治疗可能在该个体中诱导了由狭窄的特异性细胞毒性T淋巴细胞和中和抗体反应及/或其他尚未明确的因素介导的完全HIV-1控制。

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