Primary HIV-1 and Infectious Molecular Clones Are Differentially Susceptible to Broadly Neutralizing Antibodies.
Primary HIV-1 and Infectious Molecular Clones Are Differentially Susceptible to Broadly Neutralizing Antibodies.
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DOI：
10.3390/vaccines8040782
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发表时间：
2020-12-21
期刊：
影响因子：
7.8
通讯作者：
Rao M
中科院分区：
文献类型：
--
作者：
Kim J;Rao VB;Rao M
为了防止HIV-1的传播，疫苗应该引发抗体，阻止病毒进入所有类型的细胞。最近，我们开发了一种病毒捕获测定法，以定量检测感染的早期时间点。在此，我们提供了通过qRT-PCR定量的关于bNAb抑制人外周血单核细胞（PBMC）中纯化的原代急性或慢性HIV或感染性分子克隆（IMC）的捕获（1 h）或复制（48 h）的能力的数据。尽管bNAb以病毒亚型和PBMC供体特异性方式显著抑制PBMC中的HIV-1复制，但它们不抑制病毒捕获原发病毒。相比之下，PBMC和纯化的CD 4 + T细胞中的IMC捕获和复制被bNAb显著抑制，因此表明与IMC不同，原代HIV-1最初可能与其他细胞表面分子结合，这导致即使在bNAb存在下也会捕获病毒。我们的研究结果表明，最初的相互作用和感染性的主要HIV-1和IMC的某些方面是本质上不同的，这强调了在体外研究中使用主要病毒研究病毒传播的重要性，这一问题可能会影响HIV-1疫苗设计策略。
To prevent the spread of HIV-1, a vaccine should elicit antibodies that block viral entry for all cell types. Recently, we have developed a virus capture assay to quantitatively examine early time points of infection. Here we present data on the ability of bNAbs to inhibit capture (1 h) or replication (48 h) of purified primary acute or chronic HIV or infectious molecular clones (IMCs) in human peripheral blood mononuclear cells (PBMCs) as quantified by qRT-PCR. Although bNAbs significantly inhibited HIV-1 replication in PBMCs in a virus subtype and in a PBMC-donor specific manner, they did not inhibit virus capture of primary viruses. In contrast, IMC capture and replication in PBMCs and purified CD4+ T cells were significantly inhibited by bNAbs, thus indicating that unlike IMCs, primary HIV-1 may initially bind to other cell surface molecules, which leads to virus capture even in the presence of bNAbs. Our results demonstrate that the initial interactions and some aspects of infectivity of primary HIV-1 and IMCs are inherently different, which underscores the importance of studying virus transmission using primary viruses in in vitro studies, an issue that could impact HIV-1 vaccine design strategies.
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影响因子：
64.8
作者：
Huang J;Ofek G;Laub L;Louder MK;Doria-Rose NA;Longo NS;Imamichi H;Bailer RT;Chakrabarti B;Sharma SK;Alam SM;Wang T;Yang Y;Zhang B;Migueles SA;Wyatt R;Haynes BF;Kwong PD;Mascola JR;Connors M
通讯作者：
Connors M
DOI：
10.1126/science.aag0491
发表时间：
2016-09-02
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Liu J;Ghneim K;Sok D;Bosche WJ;Li Y;Chipriano E;Berkemeier B;Oswald K;Borducchi E;Cabral C;Peter L;Brinkman A;Shetty M;Jimenez J;Mondesir J;Lee B;Giglio P;Chandrashekar A;Abbink P;Colantonio A;Gittens C;Baker C;Wagner W;Lewis MG;Li W;Sekaly RP;Lifson JD;Burton DR;Barouch DH
通讯作者：
Barouch DH
影响因子：
32.4
作者：
Falkowska, Emilia;Le, Khoa M.;Ramos, Alejandra;Doores, Katie J.;Lee, Jeong Hyun;Blattner, Claudia;Ramirez, Alejandro;Derking, Ronald;van Gils, Marit J.;Liang, Chi-Hui;Mcbride, Ryan;von Bredow, Benjamin;Shivatare, Sachin S.;Wu, Chung-Yi;Chan-Hui, Po-Ying;Liu, Yan;Feizi, Ten;Zwick, Michael B.;Koff, Wayne C.;Seaman, Michael S.;Swiderek, Kristine;Moore, John P.;Evans, David;Paulson, James C.;Wong, Chi-Huey;Ward, Andrew B.;Wilson, Ian A.;Sanders, Rogier W.;Poignard, Pascal;Burton, Dennis R.
通讯作者：
Burton, Dennis R.
影响因子：
5.4
作者：
Daecke, J;Fackler, OT;Kräusslich, HG
通讯作者：
Kräusslich, HG
影响因子：
158.5
作者：
Robb, Merlin L.;Eller, Leigh A.;Michael, Nelson L.
通讯作者：
Michael, Nelson L.