Antibody-mediated protection against SHIV challenge includes systemic clearance of distal virus.
Antibody-mediated protection against SHIV challenge includes systemic clearance of distal virus.
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DOI：
10.1126/science.aag0491
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发表时间：
2016-09-02
期刊：
影响因子：
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通讯作者：
Barouch DH
中科院分区：
文献类型：
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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
HIV-1特异性广谱中和抗体（bNAbs）可保护恒河猴抵抗猴-人免疫缺陷病毒（SHIV）攻击。然而，抗体对病毒的拦截位点和抗体介导的保护机制尚不清楚。我们向恒河猴施用完全保护剂量的bNAb PGT 121，并用SHIV-SF 162 P3阴道内攻击它们。在PGT 121处理的动物中，我们在攻击后的几天内在远端组织中检测到低水平的病毒RNA和病毒DNA。病毒RNA阳性组织显示出指示先天免疫激活的转录组学变化，并且来自这些组织的细胞在过继转移到幼稚宿主中后开始感染。这些数据表明，bNAb介导的针对粘膜病毒攻击的保护可涉及清除远端组织中的感染性病毒。
HIV-1-specific broadly neutralizing antibodies (bNAbs) can protect rhesus monkeys against simian-human immunodeficiency virus (SHIV) challenge. However, the site of antibody interception of virus and the mechanism of antibody-mediated protection remain unclear. We administered a fully protective dose of the bNAb PGT121 to rhesus monkeys and challenged them intravaginally with SHIV-SF162P3. In PGT121 treated animals, we detected low levels of viral RNA and viral DNA in distal tissues for several days following challenge. Viral RNA positive tissues showed transcriptomic changes indicative of innate immune activation, and cells from these tissues initiated infection following adoptive transfer into naïve hosts. These data demonstrate that bNAb mediated protection against a mucosal virus challenge can involve clearance of infectious virus in distal tissues.