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Human immunodeficiency virus type-1 Tat protein induces secretory leukocyte protease inhibitor expression in African green monkey but not human cells.
Virus Genes ( IF 1.6 ) Pub Date : 2020-01-10 , DOI: 10.1007/s11262-020-01731-x
Selçuk Özdemir 1, 2 , Burcu Şengez 1, 3 , Alper Arslanoğlu 1
Affiliation  

African monkeys are resistant to HIV-1 infection due to intrinsic restriction mechanisms found in their cells. However, although they can be infected by monkey-adapted modified HIV-1 particles that are designed to overcome known restriction factors, virus numbers drop to undetectable levels in immunocompetent animals. These results indicate the possibility of the presence of yet unidentified factor(s) that restrict HIV-1 in old-world monkey (OWM) cells after integration of the viral genome into the host cell chromosome. In the light of these findings, we hypothesized that OWMs might have evolved resistance mechanism(s) against HIV-1 by switching specific gene(s) on in response to the synthesis of viral proteins in infected cells. In an attempt to mimic post-infection status, we expressed HIV-1 Tat gene in African green monkey cells and compared the whole proteome with normal cells and identified secretory leukocyte protease inhibitor (SLPI), a protein with known extracellular anti-HIV-1 activity, as an over-expressed protein in the presence of HIV-1 Tat protein by 2D-PAGE and mass spectrometry analysis. We also showed that overexpression of SLPI in the presence of HIV-1 Tat was specific to monkey cells. Our results also suggest that SLPI had a previously undiscovered intracellular anti-HIV activity in addition to its extracellular activity.

中文翻译:

人类免疫缺陷病毒1型Tat蛋白诱导非洲绿猴分泌白细胞蛋白酶抑制剂表达,但不诱导人细胞表达。

非洲猴由于其细胞内在的限制性机制而对HIV-1感染具有抵抗力。然而,尽管它们可以被猴子克服的改良HIV-1颗粒感染,这些颗粒被设计用来克服已知的限制因素,但在免疫能力强的动物中,病毒数量下降到了无法检测的水平。这些结果表明,在病毒基因组整合到宿主细胞染色体中后,仍可能存在限制HIV-1在旧猴(OWM)细胞中存在的不确定因素。根据这些发现,我们假设OWM可能通过响应感染细胞中病毒蛋白的合成而打开特定基因,从而发展了对HIV-1的耐药机制。为了模仿感染后的状态,我们在非洲绿猴细胞中表达了HIV-1 Tat基因,并将整个蛋白质组与正常细胞进行了比较,并确定了分泌性白细胞蛋白酶抑制剂(SLPI)(一种具有已知的细胞外抗HIV-1活性的蛋白)作为其中的过表达蛋白。 2D-PAGE和质谱分析检测HIV-1 Tat蛋白的存在。我们还显示,在HIV-1 Tat存在下SLPI的过度表达对猴细胞具有特异性。我们的结果还表明,SLPI除具有细胞外活性外,还具有以前未被发现的细胞内抗HIV活性。我们还显示,在HIV-1 Tat存在下SLPI的过表达对猴细胞具有特异性。我们的结果还表明,SLPI除具有细胞外活性外,还具有以前未被发现的细胞内抗HIV活性。我们还显示,在HIV-1 Tat存在下SLPI的过表达对猴细胞具有特异性。我们的结果还表明,SLPI除具有细胞外活性外,还具有以前未被发现的细胞内抗HIV活性。
更新日期:2020-01-10
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