Induction of indolamine 2,3-dioxygenase in primary human macrophages by human immunodeficiency virus type 1 is strain dependent
Induction of indolamine 2,3-dioxygenase in primary human macrophages by human immunodeficiency virus type 1 is strain dependent
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DOI：
10.1128/jvi.74.9.4110-4115.2000
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发表时间：
2000-05-01
影响因子：
5.4
通讯作者：
Kapoor, V
中科院分区：
文献类型：
--
作者：
Grant, RS;Naif, H;Kapoor, V
犬尿氨酸途径代谢增加与艾滋病痴呆复合体（ADC）的病因有关，该途径的限速酶是吲哚胺2,3-双加氧酶（IDO）。我们测试了不同人类免疫缺陷病毒1型（HIV1-BaL、HIV1-JRFL和HIV1-631）菌株在培养的人单核细胞源性巨噬细胞（MDM）中诱导IDO的效果，在感染脑源性HIV-1分离株、实验室适应（LA） HIV1-JRFL和原代分离株HIV1-631后48 h，观察到IDO蛋白和犬尿氨酸合成显著增加。相比之下，MDM感染中几乎没有明显的犬尿氨酸产生或IDO蛋白，具有高度复制的嗜巨噬细胞LA株HIV1-BaL。HIV1-JRFL和HIV1-631对IDO和犬尿氨酸合成的诱导作用在感染后第8天下降到基线水平，大量HIV-1复制并未降低外源性γ干扰素（ifn - γ）在感染hiv的MDM中诱导IDO和犬尿氨酸合成的能力，在感染HIV1-JRFL的MDM中添加抗ifn - γ抗体导致48 h后IDO蛋白缺失，上清犬尿氨酸浓度下降64% +/- 1%。综上所述，这些结果表明，只有选定的HIV-1菌株能够在MDM中诱导IDO合成和随后的犬尿氨酸代谢。IDO的诱导，虽然明显独立于复制能力，但似乎是由响应选定的HIV-1菌株初始感染的MDM中短暂产生ifn - γ介导的。
Increased kynurenine pathway metabolism has been implicated in the etiology of AIDS dementia complex (ADC), The rate-limiting enzyme for this pathway is indolamine 2,3-dioxygenase (IDO). We tested the efficacy of different strains of human immunodeficiency virus type 1 (HIV1-BaL, HIV1-JRFL, and HIV1-631) to induce IDO in cultured human monocyte-derived macrophages (MDM), A significant increase in both IDO protein and kynurenine synthesis was observed after 48 h in MDM infected with the brain-derived HIV-1 isolates, laboratory-adapted (LA) HIV1-JRFL, and primary isolate HIV1-631. In contrast, almost no kynurenine production or IDO protein was evident in MDM infected,vith the highly replicating macrophage tropic LA strain HIV1-BaL. The induction of IDO and kynurenine synthesis by HIV1-JRFL and HIV1-631 declined to baseline levels by day 8 postinfection, Abundant HIV-1 replication did not reduce the ability of exogenous gamma interferon (IFN-gamma) to induce IDO and kynurenine synthesis in HIV-infected MDM, The addition of anti-IFN-gamma antibody to MDM infected with HIV1-JRFL resulted in an absence of detectable IDO protein after 48 h and a decrease of 64% +/- 1% in supernatant kynurenine concentration. Together, these results indicate that only selected strains of HIV-1 are capable of inducing IDO synthesis and subsequent kynurenine metabolism in MDM, The induction of IDO, while apparently independent of replication capacity, appears to be mediated by a transient production of IFN-gamma in MDM responding to the initial infection with selected strains of HIV-1.