SERINC5 as a New Restriction Factor for Human Immunodeficiency Virus and Murine Leukemia Virus
SERINC5 as a New Restriction Factor for Human Immunodeficiency Virus and Murine Leukemia Virus
复制标题
DOI：
10.1146/annurev-virology-092917-043308
复制
发表时间：
2018-01-01
期刊：
影响因子：
--
通讯作者：
Pizzato, Massimo
中科院分区：
文献类型：
--
作者：
Firrito, Claudia;Bertelli, Cinzia;Pizzato, Massimo
SERINC基因编码具有未知细胞功能的同源多通道跨膜蛋白，尽管在真核生物中高度保守。在人类发现的五种SERINC基因中，SERINC 5被证明是一种强大的逆转录病毒抑制剂。它被有效地整合到病毒体中，并通过以尚不清楚的机制损害融合过程来阻断病毒核心渗透到靶细胞中。还发现SERINC 5促进抗体对人类免疫缺陷病毒1（HIV-1）病毒粒子的中和，表明其具有多效性活性，这一点大多尚未探索。对抗因子已经独立地出现在至少三种逆转录病毒谱系中，强调了它们在逆转录病毒进化过程中的根本重要性。灵长类和马慢病毒的Nef和S2以及γ逆转录病毒的glycoGag通过将SERINC 5靶向到内体并将其从病毒体中排除而起类似作用。在这里，我们讨论了区分SERINC 5与其他已知限制因子的特征，描绘了一类独特的抗病毒抑制剂。
SERINC genes encode for homologous multipass transmembrane proteins with unknown cellular function, despite being highly conserved across eukaryotes. Among the five SERINC genes found in humans, SERINC5 was shown to act as a powerful inhibitor of retroviruses. It is efficiently incorporated into virions and blocks the penetration of the viral core into target cells, by impairing the fusion process with a yet unclear mechanism. SERINC5 was also found to promote human immunodeficiency virus 1 (HIV-1) virion neutralization by antibodies, indicating a pleiotropic activity, which remains mostly unexplored. Counteracting factors have emerged independently in at least three retrovirus lineages, underscoring their fundamental importance during retrovirus evolution. Nef and S2 of primate and equine lentiviruses, and glycoGag of gammaretroviruses, act similarly by targeting SERINC5 to endosomes and excluding it from virions. Here, we discuss the features that distinguish SERINC5 from other known restriction factors, delineating a yet unique class of antiviral inhibitors.