Luttge Benjamin G, Freed Eric O
Virus-Cell Interaction Section, HIV Drug Resistance Program, National Cancer Institute at Frederick, Frederick, MD 21702-1201, USA.
Vet Immunol Immunopathol. 2010 Mar 15;134(1-2):3-13. doi: 10.1016/j.vetimm.2009.10.003. Epub 2009 Oct 14.
Infection of domestic cats with virulent strains of the feline immunodeficiency virus (FIV) leads to an acquired immunodeficiency syndrome (AIDS), similar to the pathogenesis induced in humans by infection with human immunodeficiency virus type 1 (HIV-1). Thus, FIV is a highly relevant model for anti-HIV therapy and vaccine development. FIV is not infectious in humans, so it is also a potentially effective non-toxic gene therapy vector. To make better use of this model, it is important to define the cellular machinery utilized by each virus to produce virus particles so that relevant similarities can be identified. It is well understood that all replication-competent retroviruses encode gag, pol, and env genes, which provide core elements for virus replication. As a result, most antiretroviral therapy targets pol-derived enzymes (protease, reverse transcriptase, and integrase) orenv-derived glycoproteins that mediate virus attachment and entry. However, resistance to drugs against these targets is a persistent problem, and novel targets must be identified to produce more effective drugs that can either substitute or be combined with current therapy. Elements of the gag gene (matrix, capsid, nucleocapsid, and "late" domains) have yet to be exploited as antiviral targets, even though the Gag precursor polyprotein is self-sufficient for the assembly and release of virus particles from cells. This process is far better understood in primate lentiviruses, especially HIV-1. However, there has been significant progress in recent years in defining how FIV Gag is targeted to the cellular plasma membrane, assembles into virions, incorporates FIV Env glycoproteins, and utilizes host cell machinery to complete virus release. Recent discoveries of intracellular restriction factors that target HIV-1 and FIV capsids after virus entry have also opened exciting new areas of research. This review summarizes currently known interactions involving HIV-1 and FIV Gag that affect virus release, infectivity, and replication.
家猫感染猫免疫缺陷病毒（FIV）的强毒株会导致获得性免疫缺陷综合征（AIDS），其发病机制与人类感染1型人类免疫缺陷病毒（HIV-1）所引发的相似。因此，FIV是抗HIV治疗和疫苗研发的高度相关模型。FIV对人类无传染性，所以它也是一种潜在有效的无毒基因治疗载体。为了更好地利用这个模型，明确每种病毒用于产生病毒颗粒的细胞机制以便识别相关相似性很重要。众所周知，所有具有复制能力的逆转录病毒都编码gag、pol和env基因，这些基因提供了病毒复制的核心元件。因此，大多数抗逆转录病毒疗法针对pol衍生的酶（蛋白酶、逆转录酶和整合酶）或介导病毒附着和进入的env衍生糖蛋白。然而，对针对这些靶点的药物产生耐药性是一个持续存在的问题，必须识别新的靶点以生产出能替代当前疗法或与当前疗法联合使用的更有效药物。gag基因的元件（基质、衣壳、核衣壳和“晚期”结构域）尚未被用作抗病毒靶点，尽管Gag前体多聚蛋白对于从细胞中组装和释放病毒颗粒是自给自足的。在灵长类慢病毒尤其是HIV-1中，这个过程已得到更好的理解。然而，近年来在确定FIV Gag如何靶向细胞质膜、组装成病毒体、整合FIV Env糖蛋白以及利用宿主细胞机制完成病毒释放方面取得了重大进展。最近发现的在病毒进入后靶向HIV-1和FIV衣壳的细胞内限制因子也开辟了令人兴奋的新研究领域。本综述总结了目前已知的涉及HIV-1和FIV Gag的相互作用，这些相互作用影响病毒释放、感染性和复制。
