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人类和动物逆转录病毒中的外壳紊乱、免疫逃逸及传播行为。

Shell disorder, immune evasion and transmission behaviors among human and animal retroviruses.

作者信息

Goh Gerard Kian-Meng, Dunker A Keith, Uversky Vladimir N

机构信息

Goh's BioComputing, Singapore, Republic of Singapore.

出版信息

Mol Biosyst. 2015 Aug;11(8):2312-23. doi: 10.1039/c5mb00277j.

Abstract

This study involves measurements of percentages of intrinsic disorder (PIDs) in the GAG protein shells of various retroviruses. Unique patterns of shell protein disorder can be seen especially when GAG proteins (matrix M, capsid C, and nucleocapsid N) of primate and non-primate retroviruses are compared. HIV-1 presents the most unique pattern of disorder distribution with generally high levels of disorder in all three proteins, while EIAV (PIDs:: 26, 29, 13) is diametrically different from HIV-1 (N C M PIDs: 39.5 ± 3.0, 44.5 ± 2.6, 56.5 ± 10.8). The HTLV viruses (CPID: 32.8 ± 3.4) resemble HIV-2 (C PID: 26.6 ± 2.9) with a moderately disordered capsid. Totally distinct patterns, however, are seen for the non-primate retroviruses. They generally have highly disordered nucleocapsids (PID > 65%) and more ordered outer shells especially the matrix. These characteristics might be attributed to the differences in the way the retroviruses are transmitted, with non-primate viruses having greater non-sexual transmission components such as oral-fecal transmission. These differences are also evolutionarily related to the ways the viruses evade the host immune systems, and thus, have implications for oncolytic virotherapy and animal models in vaccine research. The importance of protein shell disorder in immune evasion, as related to the case of HIV-1, and the difficult search for its vaccines are highlighted.

摘要

本研究涉及对各种逆转录病毒的GAG蛋白衣壳中内在无序百分比(PID)的测量。当比较灵长类和非灵长类逆转录病毒的GAG蛋白(基质M、衣壳C和核衣壳N)时,可以看到衣壳蛋白无序的独特模式。HIV-1呈现出最独特的无序分布模式,所有三种蛋白中的无序水平普遍较高,而马传染性贫血病毒(EIAV,PID分别为26、29、13)与HIV-1截然不同(N、C、M的PID分别为:39.5±3.0、44.5±2.6、56.5±10.8)。人嗜T淋巴细胞病毒(CPID为32.8±3.4)与HIV-2(C的PID为26.6±2.9)相似,衣壳具有中等程度的无序。然而,非灵长类逆转录病毒呈现出完全不同的模式。它们通常具有高度无序的核衣壳(PID>65%)和更有序的外壳,尤其是基质。这些特征可能归因于逆转录病毒传播方式的差异,非灵长类病毒具有更大的非性传播成分,如粪口传播。这些差异在进化上也与病毒逃避宿主免疫系统的方式有关,因此,对溶瘤病毒疗法和疫苗研究中的动物模型具有重要意义。强调了蛋白衣壳无序在免疫逃逸中的重要性,这与HIV-1的情况相关,以及寻找其疫苗的困难。

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