Iyengar Sujatha, Schwartz David H
Department of Molecular Microbiology and Immunology, The Bloomberg School of Public Health, Johns Hopkins University , Baltimore, Maryland.
AIDS Res Hum Retroviruses. 2011 May;27(5):519-23. doi: 10.1089/AID.2010.0131. Epub 2010 Nov 23.
Abstract R5 and X4 HIV strains use CCR5 or CXCR4 chemokine receptors (CKRs), respectively, for entry. Preferential growth of X4 vs. R5 HIV in cell lines reflects constitutive expression of CXCR4, but not CCR5 (in contrast to dual expression on primary T cells), and CXCR4 is the predominant CKR found on most tumors. Non-Hodgkin's B cell lymphomas (NHL) are increased among HIV(+) patients, and interactions between HIV envelope and CKRs may contribute to lymphomagenesis. Despite strong evidence for a CXCR4-SDF-1 oncogenic axis, no in vitro evaluation of CXCR4-mediated normal lymphocyte transformation has been published. Exposure of normal B cells to EBV in the presence of X4 gp120 (but not R5 gp120) increased proliferation and BLCL outgrowth, comparable to anti-CD40 mAb costimulation. This suggests a role for X4 tropic viral envelope signaling via CXCR4 and/or CXCR7 in HIV-associated lymphomagenesis.
R5和X4型HIV毒株分别利用CCR5或CXCR4趋化因子受体（CKR）进入细胞。X4型HIV在细胞系中相对于R5型HIV的优先生长反映了CXCR4的组成性表达，而非CCR5（与原代T细胞上的双表达相反），并且CXCR4是大多数肿瘤中发现的主要CKR。非霍奇金B细胞淋巴瘤（NHL）在HIV阳性患者中有所增加，HIV包膜与CKR之间的相互作用可能有助于淋巴瘤的发生。尽管有强有力的证据支持CXCR4-SDF-1致癌轴，但尚未发表关于CXCR4介导的正常淋巴细胞转化的体外评估。在X4 gp120（而非R5 gp120）存在的情况下，正常B细胞暴露于EBV会增加增殖和B淋巴母细胞样细胞系（BLCL）的生长，这与抗CD40单克隆抗体共刺激相当。这表明X4嗜性病毒包膜通过CXCR4和/或CXCR7发出的信号在HIV相关淋巴瘤发生中起作用。
