Induction of neutralizing antibodies against tier 2 human immunodeficiency virus 1 in rhesus macaques infected with tier 1B simian/human immunodeficiency virus
Induction of neutralizing antibodies against tier 2 human immunodeficiency virus 1 in rhesus macaques infected with tier 1B simian/human immunodeficiency virus
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在感染 1B 级猿/人类免疫缺陷病毒的恒河猴中诱导针对 2 级人类免疫缺陷病毒 1 的中和抗体
DOI：
10.1007/s00705-019-04173-5
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发表时间：
2019
影响因子：
2.7
通讯作者：
Miura Tomoyuki
中科院分区：
文献类型：
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作者：
Himeno Ai;Ishida Yuki;Mori Hiromi;Matsuura Kanako;Kikukawa Minako;Sakawaki Hiromi;Miura Tomoyuki
我们以前开发了CCR 5嗜中性中和抗性猿猴/人类免疫缺陷病毒（SHIV）株和恒河猴感染这些SHIV的模型。我们通过感染不同中和抗性的SHIV毒株来诱导产生针对HIV-1的中和抗体（nAbs）。首先，使用CXCR 4作为主要共受体，从SHIV-KS 661产生具有CCR 5向性的SHIV-MK 1（MK 1）（中和敏感，1B级）。通过恒河猴MM 482的1B级病毒（MK 1）感染诱导针对亲本谱系和异源2级病毒的nAb。我们分析了MM 482中随时间推移的病毒对中和的抗性，并观察到感染病毒在感染后36周（wpi）从1B级突变为2级。此外，突变分析显示N169 D、K187 E、S190 N、S239、T459 N（T459 D在91 wpi）和V842 A突变在36 wpi后存在。这导致了耐中和病毒克隆的出现。此外，MK 1在三只恒河猴中传代，以产生中和抗性SHIV-MK 38（MK 38）（2级）。我们评估了感染SHIV-MK 38 #818（#818）（2级）（MK 38的分子克隆）的恒河猴的nAb产生。与感染1B级病毒的猕猴相比，诱导了亲本谱系的中和，并且开始产生针对异源2级病毒的中和活性。因此，CCR 5嗜性中和抗性SHIV感染的恒河猴可能是抗HIV-1 nAb生产的有用模型，并将促进开发针对HIV-1的elevin-nAb疫苗。
We previously developed CCR5-tropic neutralization-resistant simian/human immunodeficiency virus (SHIV) strains and a rhesus macaque model of infection with these SHIVs. We induced the production of neutralizing antibodies (nAbs) against HIV-1 by infecting rhesus macaques with different neutralization-resistant SHIV strains. First, SHIV-MK1 (MK1) (neutralization susceptible, tier 1B) with CCR5 tropism was generated from SHIV-KS661 using CXCR4 as the main co-receptor. nAbs against parental-lineage and heterologous tier 2 viruses were induced by tier 1B virus (MK1) infection of the rhesus macaque MM482. We analyzed viral resistance to neutralization over time in MM482 and observed that the infecting virus mutated from tier 1B to tier 2 at 36 weeks postinfection (wpi). In addition, an analysis of mutations showed that N169D, K187E, S190N, S239, T459N (T459D at 91 wpi), and V842A mutations were present after 36 wpi. This led to the appearance of neutralization-resistant viral clones. In addition, MK1 was passaged in three rhesus macaques to generate neutralization-resistant SHIV-MK38 (MK38) (tier 2). We evaluated nAb production by rhesus macaques infected with SHIV-MK38 #818 (#818) (tier 2), a molecular clone of MK38. Neutralization of the parental lineage was induced earlier than in macaques infected with tier 1B virus, and neutralization activity against heterologous tier 2 virus was beginning to develop. Therefore, CCR5-tropic neutralization-resistant SHIV-infected rhesus macaques may be useful models of anti-HIV-1 nAb production and will facilitate the development of a vaccine that elicits nAbs against HIV-1.