Role of the Feline Immunodeficiency Virus L-Domain in the Presence or Absence of Gag Processing: Involvement of Ubiquitin and Nedd4-2s Ligase in Viral Egress
Role of the Feline Immunodeficiency Virus L-Domain in the Presence or Absence of Gag Processing: Involvement of Ubiquitin and Nedd4-2s Ligase in Viral Egress
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DOI：
10.1002/jcp.21587
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发表时间：
2009-01-01
影响因子：
5.6
通讯作者：
Parolin, Cristina
中科院分区：
文献类型：
--
作者：
Calistri, Arianna;Del Vecchio, Claudia;Parolin, Cristina
RNA包膜病毒通过利用多泡体（MVB）途径从感染的细胞中出芽。在这种情况下，结构病毒蛋白的泛素化及其与参与MVB生物发生的细胞因子通过短的富含脯氨酸的区域（称为晚期结构域（L-结构域））的直接相互作用是至关重要的机制。在这里，我们报告说，与人类免疫缺陷病毒（HIV），猫免疫缺陷病毒（FIV），非灵长类慢病毒，是严格依赖于其萌芽上的“PSAP”型的L-结构域，映射在羧基末端区域的Gag，无论一个功能性的病毒蛋白酶。此外，我们提供的证据表明，FIV出口相关的Gag泛素化，也就是说，链接到一个活跃的L-结构域的存在。最后，虽然FIV Gag不包含PPxY基序，但我们表明Nedd 4 -2s泛素连接酶增强FIV Gag泛素化，并且能够拯救缺乏功能性L结构域的病毒突变体。总之，我们的数据揭示了FIV出口的特殊方面，但我们也证明了非灵长类慢病毒与HIV-1共享一种与细胞出芽机制连接的新机制。
RNA-enveloped viruses bud from infected cells by exploiting the multivesicular body (MVB) pathway. In this context, ubiquitination of structural viral proteins and their direct interaction with cellular factors involved in the MVB biogenesis through short proline rich regions, named late domains (L-domains), are crucial mechanisms. Here we report that, in contrast with the human immunodeficiency virus (HIV), the feline immunodeficiency virus (FIV), a non-primate lentivirus, is strictly dependent for its budding on a "PSAP"-type L-domain, mapping in the carboxy-terminal region of Gag, irrespective of a functional viral protease. Moreover, we provide evidence that FIV egress is related to Gag ubiquitination, that is, linked to the presence of an active L-domain. Finally, although FIV Gag does not contain a PPxY motif, we show that the Nedd4-2s ubiquitin ligase enhances FIV Gag ubiquitination and it is capable to rescue viral mutants lacking a functional L-domain. In conclusion, our data bring to light peculiar aspects of FIV egress, but we also demonstrate that a non-primate lentivirus shares with HIV-1 a novel mechanism of connection to the cellular budding machinery.