Human immunodeficiency virus type 1 gp120 stimulates cytomegalovirus replication in monocytes: Possible role of endogenous interleukin-8
Human immunodeficiency virus type 1 gp120 stimulates cytomegalovirus replication in monocytes: Possible role of endogenous interleukin-8
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DOI：
10.1128/jvi.71.2.1591-1597.1997
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发表时间：
1997-02-01
影响因子：
5.4
通讯作者：
Dianzani, F
中科院分区：
文献类型：
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作者：
Capobianchi, MR;Barresi, C;Dianzani, F
重组gp120，而不是其他人类免疫缺陷1型（HIV-1）结构蛋白，剂量依赖性地刺激新分离的感染HCMV的正常单核细胞中人巨细胞病毒（HCMV）即刻早期抗原（IEA）的表达和感染性病毒的产量。单克隆抗体（mab）识别gp120 V3环，以及V3环八聚体多支肽和半乳糖脑苷抗体，但不识别sCD4，可以消除gp120对IEA表达的刺激，这表明这种作用涉及V3环-半乳糖脑苷相互作用，而不是由CD4介导的。gp120处理单核细胞后，白细胞介素8 （IL-8）基因在mRNA和释放蛋白水平上表达增强。外源性IL-8可以替代gp120刺激HCMV感染，而能够中和IL-8活性的单抗可以消除gp120诱导的HCMV刺激。这些数据表明，HIV-1糖蛋白诱导HCMV单核细胞生产性感染的刺激，这种刺激可能是通过上调IL-8基因表达介导的。这是第一个证明HIV-1可能间接影响HCMV复制的证据，通过gp120与单核细胞膜的相互作用，在完全没有逆转录病毒复制的情况下，通过刺激IL-8的释放。因为在hiv -1感染的个体中，HCMV感染经常被激活，循环IL-8水平增强，这些发现可能与病理相关。
Recombinant gp120, but not other human immunodeficiency type 1 (HIV-1) structural proteins, dose-dependently stimulates human cytomegalovirus (HCMV) immediate-early antigen (IEA) expression and infectious virus yield in freshly isolated normal monocytes infected with HCMV. Monoclonal antibodies (MAbs) recognizing the gp120 V3 loop, as well as V3 loop octameric multibranched peptides and antibody to galactocerebroside, but not sCD4, abrogate the gp120 stimulation of IEA expression, suggesting that the effect involves V3 loop-galactocerebroside interaction and is not mediated by CD4. Interleukin 8 (IL-8) gene expression is enhanced in monocytes treated with gp120 at the level of both mRNA and released protein. Exogenous IL-8 could replace gp120 in the stimulation of HCMV infection, while a MAb capable of neutralizing IL-8 activity abrogates the gp120-induced HCMV stimulation. These data indicate that HIV-1 glycoprotein induces stimulation of productive infection of monocytes with HCMV and that such stimulation may be mediated by the upregulation of IL-8 gene expression. This is the first evidence that HIV-1 may affect HCMV replication indirectly, via the interaction of gp120 with the monocyte membrane, in the complete absence of retroviral replication, through the stimulation of IL-8 release. Because in HIV-1-infected individuals, HCMV infection is frequently activated and the levels of circulating IL-8 are enhanced, these findings may be pathogenetically relevant.