Identification of three major phosphorylation sites within HIV-1 capsid - Role of phosphorylation during the early steps of infection
Identification of three major phosphorylation sites within HIV-1 capsid - Role of phosphorylation during the early steps of infection
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DOI：
10.1074/jbc.274.27.19434
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发表时间：
1999-07-02
影响因子：
4.8
通讯作者：
Boyer, V
中科院分区：
文献类型：
--
作者：
Cartier, C;Sivard, P;Boyer, V
我们以前报道的存在下，两个细胞的丝氨酸/苏氨酸蛋白激酶纳入人类免疫缺陷病毒1型（HIV-1）的颗粒。一种蛋白激酶是MAPK ERK 2（丝裂原活化蛋白激酶），而另一种是53 kDa的蛋白，仍需鉴定。此外，我们证明衣壳蛋白CAp 24被这两种病毒体相关蛋白激酶之一磷酸化（Cartier，C.，Deckert，M.，Grangeasse，C.，特劳格河，詹森，F.，Bernard，k，Cozzone，k，Desgranges，C.，和Boyer，V.（1997）J. Virol. 71，4832-4837）。在这项研究中，我们发现CAp 24不是MAPK ERK 2的直接底物。此外，使用CAp 24的9个丝氨酸残基中的每一个的定点诱变，我们证明了CAp 24中的3个丝氨酸残基（Ser-109、Ser-149和Ser-178）的磷酸化。每个丝氨酸残基的取代不影响病毒出芽，也不影响病毒结构。相比之下，Ser-109、Ser-149或Ser-178的取代通过阻止逆转录过程完全实现而影响病毒感染性。我们的研究结果表明，CAp 24丝氨酸磷酸化是必不可少的病毒脱壳过程。
We previously reported the presence of two cellular serine/threonine protein kinases incorporated in human immunodeficiency virus type 1 (HIV-1) particles. One protein kinase is MAPK ERK2 (mitogen-activated protein kinase), whereas the other one, a 53-kDa protein, still needs to be identified. Furthermore, we demonstrated that the capsid protein CAp24 is phosphorylated by one of those two virion-associated protein kinases (Cartier, C., Deckert, M., Grangeasse, C., Trauger, R., Jensen, F., Bernard, k, Cozzone, k, Desgranges, C., and Boyer, V. (1997) J. Virol. 71, 4832-4837). In this study, we showed that CAp24 is not a direct substrate of MAPK ERK2. Moreover, using site-directed mutagenesis of each of the 9 serine residues of CAp24, we demonstrated the phosphorylation of 3 serine residues (Ser-109, Ser-149, and Ser-178) in the CAp24. Substitution of each serine residue did not affect viral budding, nor viral structure. By contrast, substitution of Ser-109, Ser-149, or Ser-178 affects viral infectivity by preventing the reverse transcription process to be completely achieved. Our results suggest that CAp24 serine phosphorylation is essential for viral uncoating process.