Influence of Different Glycoproteins and of the Virion Core on SERINC5 Antiviral Activity.

Influence of Different Glycoproteins and of the Virion Core on SERINC5 Antiviral Activity.
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DOI:
10.3390/v13071279
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发表时间:
2021-06-30
期刊:
Viruses
影响因子:
--
通讯作者:
Luban J
Luban J
中科院分区:
其他
文献类型:
--
作者:
Diehl WE;Guney MH;Vanzo T;Kyawe PP;White JM;Pizzato M;Luban J

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宿主质膜蛋白 SERINC5 被整合到出芽的逆转录病毒颗粒中,阻止随后进入易感靶细胞。由不同逆转录病毒、人类免疫缺陷病毒 1 型 (HIV-1) Nef、马传染性贫血病毒 (EIAV) S2 和亲嗜性鼠白血病病毒 (MLV) GlycoGag 编码的三种结构上不相关的蛋白质,通过将 SERINC5 从质膜上的病毒粒子组装位点重定向到内部 RAB7+ 内体隔室,破坏 SERINC5 的抗病毒活性。用特定糖蛋白(例如水泡性口炎病毒糖蛋白(VSV G))对逆转录病毒进行假型化,使颗粒的感染性对病毒粒子相关的 SERINC5 的抑制具有抵抗力。为了更好地了解 SERINC5 敏感性的病毒决定因素,使用 HIV-1、MLV 和 Mason-Pfizer 猴病毒 (M-PMV) 病毒颗粒核心评估了 SERINC5 的影响,这些病毒颗粒核心采用沙粒病毒、冠状病毒、丝状病毒、弹状病毒、副粘病毒和正粘病毒属的糖蛋白进行假型化。 SERINC5 限制性病毒粒子用来自几种逆转录病毒、正粘病毒、弹状病毒、副粘病毒和沙粒病毒的糖蛋白假型化。无论核心是由 HIV-1、MLV 还是 M-PMV 提供,SERINC5 都会降低用 HIV-1、双嗜性 MLV (A-MLV) 或甲型流感病毒 (IAV) 糖蛋白假型化的颗粒的感染性。相比之下,用来自 M-PMV、副流感病毒 5 (PIV5) 或狂犬病病毒 (RABV) 的糖蛋白假型化的颗粒对 SERINC5 敏感,但仅具有特定的逆转录病毒核心。对 SERINC5 的抗性与 SERINC5 掺入颗粒的减少、病毒进入途径或假型病毒颗粒的绝对感染性无关。这些发现表明,一些非逆转录病毒可能对 SERINC5 敏感,并且除了病毒糖蛋白之外,逆转录病毒核心也会影响对 SERINC5 的敏感性。
Host plasma membrane protein SERINC5 is incorporated into budding retrovirus particles where it blocks subsequent entry into susceptible target cells. Three structurally unrelated proteins encoded by diverse retroviruses, human immunodeficiency virus type 1 (HIV-1) Nef, equine infectious anemia virus (EIAV) S2, and ecotropic murine leukemia virus (MLV) GlycoGag, disrupt SERINC5 antiviral activity by redirecting SERINC5 from the site of virion assembly on the plasma membrane to an internal RAB7+ endosomal compartment. Pseudotyping retroviruses with particular glycoproteins, e.g., vesicular stomatitis virus glycoprotein (VSV G), renders the infectivity of particles resistant to inhibition by virion-associated SERINC5. To better understand viral determinants for SERINC5-sensitivity, the effect of SERINC5 was assessed using HIV-1, MLV, and Mason-Pfizer monkey virus (M-PMV) virion cores, pseudotyped with glycoproteins from Arenavirus, Coronavirus, Filovirus, Rhabdovirus, Paramyxovirus, and Orthomyxovirus genera. SERINC5 restricted virions pseudotyped with glycoproteins from several retroviruses, an orthomyxovirus, a rhabdovirus, a paramyxovirus, and an arenavirus. Infectivity of particles pseudotyped with HIV-1, amphotropic-MLV (A-MLV), or influenza A virus (IAV) glycoproteins, was decreased by SERINC5, whether the core was provided by HIV-1, MLV, or M-PMV. In contrast, particles pseudotyped with glycoproteins from M-PMV, parainfluenza virus 5 (PIV5), or rabies virus (RABV) were sensitive to SERINC5, but only with particular retroviral cores. Resistance to SERINC5 did not correlate with reduced SERINC5 incorporation into particles, route of viral entry, or absolute infectivity of the pseudotyped virions. These findings indicate that some non-retroviruses may be sensitive to SERINC5 and that, in addition to the viral glycoprotein, the retroviral core influences sensitivity to SERINC5.
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