Adaptation to the Interferon-Induced Antiviral State by Human and Simian Immunodeficiency Viruses
Adaptation to the Interferon-Induced Antiviral State by Human and Simian Immunodeficiency Viruses
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DOI：
10.1128/jvi.03219-12
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发表时间：
2013-03-01
影响因子：
5.4
通讯作者：
Hatziioannou, Theodora
中科院分区：
文献类型：
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作者：
Bitzegeio, Julia;Sampias, Marissa;Hatziioannou, Theodora
I型干扰素（IFN）的产生是宿主对不同感染因子的早期反应，导致数百种干扰素刺激基因（isg）的诱导。许多isg在宿主防御中的作用尚不清楚，但它们的表达导致诱导“抗病毒状态”，抑制许多病毒的复制。在这里，我们发现灵长类慢病毒人类免疫缺陷病毒1型（HIV-1）和猕猴猴免疫缺陷病毒（SIVMAC和SIVMNE）的原型可以在其通常宿主（分别是人类和猕猴）的淋巴细胞中复制，即使在ifn - α治疗诱导抗病毒状态时也是如此。相比之下，HIV-1和SIVMAC/SIVMNE复制对非自然宿主淋巴细胞中的ifn - α敏感，这表明抗病毒状态可以有效地抑制灵长类慢病毒在它们不适应的宿主中的复制。自然产生的HIV-1和HIV-2毒株的大多数成员表现得像原型毒株，对人类淋巴细胞中的ifn - α相对不敏感。利用嵌合病毒来克服限制因子，其抗逆转录病毒特异性以物种依赖的方式变化，我们证明了人类和猕猴淋巴细胞中HIV-1和SIVMAC对ifn - α的不同敏感性不能归因于TRIM5、APOBEC3、tetherin或SAMHD1。单周期感染实验表明，至少部分这种物种特异性的、ifn - α诱导的灵长类慢病毒复制限制发生在逆转录病毒生命周期的早期。总的来说，这些研究表明存在未发现的ifn α诱导的抗逆转录病毒因子，其活性谱以物种依赖的方式变化，并且至少一些HIV/SIV毒株已经在其通常的宿主中适应了这些因子。
The production of type I interferon (IFN) is an early host response to different infectious agents leading to the induction of hundreds of IFN-stimulated genes (ISGs). The roles of many ISGs in host defense are unknown, but their expression results in the induction of an "antiviral state" that inhibits the replication of many viruses. Here we show that prototype primate lentiviruses human immunodeficiency virus type 1 (HIV-1) and simian immunodeficiency virus of macaques (SIVMAC and SIVMNE) can replicate in lymphocytes from their usual hosts (humans and macaques, respectively), even when an antiviral state is induced by IFN-alpha treatment. In contrast, HIV-1 and SIVMAC/SIVMNE replication was hypersensitive to IFN-alpha in lymphocytes from unnatural hosts, indicating that the antiviral state can effectively curtail the replication of primate lentiviruses in hosts to which they are not adapted. Most of the members of a panel of naturally occurring HIV-1 and HIV-2 strains behaved like prototype strains and were comparatively insensitive to IFN-alpha in human lymphocytes. Using chimeric viruses engineered to overcome restriction factors whose antiretroviral specificities vary in a species-dependent manner, we demonstrate that differential HIV-1 and SIVMAC sensitivities to IFN-alpha in lymphocytes from humans and macaques could not be ascribed to TRIM5, APOBEC3, tetherin, or SAMHD1. Single-cycle infection experiments indicated that at least part of this species-specific, IFN-alpha-induced restriction of primate lentivirus replication occurs early in the retroviral life cycle. Overall, these studies indicate the existence of undiscovered, IFN-alpha-inducible antiretroviral factors whose spectrum of activity varies in a species-dependent manner and to which at least some HIV/SIV strains have become adapted in their usual hosts.