Department of Virology and Preventive Medicine, Gunma University Graduate School of Medicine, Maebashi, Gunma, Japan.
PLoS One. 2013 Aug 29;8(8):e73116. doi: 10.1371/journal.pone.0073116. eCollection 2013.
More than 12 chemokine receptors (CKRs) have been identified as coreceptors for the entry of human immunodeficiency virus type 1 (HIV-1), type 2 (HIV-2), and simian immunodeficiency viruses (SIVs) into target cells. The expression of CC chemokine receptor 6 (CCR6) on Th17 cells and regulatory T cells make the host cells vulnerable to HIV/SIV infection preferentially. However, only limited information is available concerning the specific role of CCR6 in HIV/SIV infection. We examined CCR6 as a coreceptor candidate in this study using NP-2 cell line-based in-vitro studies. Normally, CD4-transduced cell line, NP-2/CD4, is strictly resistant to all HIV/SIV infection. When CCR6 was transduced there, the resultant NP-2/CD4/CCR6 cells became susceptible to HIV-1HAN2, HIV-2MIR and SIVsmE660, indicating coreceptor roles of CCR6. Viral antigens in infected cells were detected by IFA and confirmed by detection of proviral DNA. Infection-induced syncytia in NP-2/CD4/CCR6 cells were detected by Giemsa staining. Amount of virus release through CCR6 has been detected by RT assay in spent culture medium. Sequence analysis of proviral DNA showed two common amino acid substitutions in the C2 envelope region of HIV-2MIR clones propagated through NP-2/CD4/CCR6 cells. Conversely, CCR6-origin SIVsmE660 clones resulted two amino acid changes in the V1 region and one change in the C2 region. The substitutions in the C2 region for HIV-2MIR and the V1 region of SIVsmE660 may confer selection advantage for CCR6-use. Together, the results describe CCR6 as an independent coreceptor for HIV and SIV in strain-specific manner. The alteration of CCR6 uses by viruses may influence the susceptibility of CD4+ CCR6+ T-cells and dendritic cell subsets in vivo and therefore, is important for viral pathogenesis in establishing latent infections, trafficking, and transmission. However, clinical relevance of CCR6 as coreceptor in HIV/SIV infections should be investigated further.
已鉴定出超过 12 种趋化因子受体（CKR）作为人类免疫缺陷病毒 1 型（HIV-1）、2 型（HIV-2）和猴免疫缺陷病毒（SIV）进入靶细胞的辅助受体。CC 趋化因子受体 6（CCR6）在 Th17 细胞和调节性 T 细胞上的表达使宿主细胞易受 HIV/SIV 感染。然而，关于 CCR6 在 HIV/SIV 感染中的具体作用，仅有有限的信息。我们在这项研究中使用基于 NP-2 细胞系的体外研究来研究 CCR6 作为辅助受体候选物。通常情况下，CD4 转导的细胞系 NP-2/CD4 严格抵抗所有 HIV/SIV 感染。当 CCR6 转导到那里时，产生的 NP-2/CD4/CCR6 细胞变得易受 HIV-1HAN2、HIV-2MIR 和 SIVsmE660 的感染，表明 CCR6 具有辅助受体作用。通过 IFA 检测感染细胞中的病毒抗原，并通过检测前病毒 DNA 进行确认。用 Giemsa 染色检测 NP-2/CD4/CCR6 细胞中的感染诱导合胞体。通过 RT 测定法在耗竭的培养物中检测通过 CCR6 释放的病毒量。对通过 NP-2/CD4/CCR6 细胞传播的 HIV-2MIR 克隆的前病毒 DNA 进行序列分析显示，在 C2 包膜区有两个常见的氨基酸取代。相反，CCR6 起源的 SIVsmE660 克隆在 V1 区有两个氨基酸变化和 C2 区一个变化。HIV-2MIR 的 C2 区和 SIVsmE660 的 V1 区的替换可能赋予 CCR6 利用的选择优势。总之，这些结果描述了 CCR6 作为 HIV 和 SIV 的独立辅助受体，具有菌株特异性。病毒对 CCR6 利用的改变可能会影响体内 CD4+CCR6+T 细胞和树突状细胞亚群的易感性，因此对建立潜伏感染、转移和传播中的病毒发病机制很重要。然而，需要进一步研究 CCR6 作为 HIV/SIV 感染中的辅助受体的临床相关性。
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