人類胞嘧啶脫氨酶APOBEC3F(A3F)及APOBEC3G(A3G)抑制了人類免疫缺陷病毒1型(HIV-1)的復(fù)制,。當(dāng)缺乏HIV-1 Vif（Vif對HIV并非必不可少,，但可能影響游離HIV感染性、病毒體的產(chǎn)生和體內(nèi)傳播）時,，A3F/A3G合并組裝病毒顆粒,，并在隨后被感染的靶細胞發(fā)揮抗病毒功能。
A3F及A3G合并成病毒顆粒,，隨后在蛋白酶成熟的病毒顆粒核心內(nèi)的形成衣殼化,，這些作用有可能對這些蛋白的抗病毒功能是重要的。在這篇文章中,，美國范德堡大學(xué)醫(yī)學(xué)院John P. Donahue等人闡明了在成熟的病毒顆粒核心A3F被定量衣殼化的機制,。相關(guān)論文發(fā)表在3月28日的The Journal of Biological Chemistry。
與A3F顯著的不同,，A3G分布在病毒顆粒核心內(nèi)及核心外,。通過分析一系列包含N端及C端脫氨基酶的A3F-A3G嵌合體，鑒定了一個位于A3F的C末端脫氨酶結(jié)構(gòu)域的14個氨基酸片段,，發(fā)現(xiàn)它可以促進優(yōu)先的衣殼化及抗HIV活性,。位于這個C端區(qū)域的氨基酸殘基L306被發(fā)現(xiàn)對這些功能是必需的但不是充分的。在N端脫氨酶結(jié)構(gòu)域的氨基酸殘基W126被發(fā)現(xiàn)也促進了優(yōu)先的衣殼化以及A3F的抗病毒活性,。對A3F（W126A L306A)雙重突變株的分析表明,，這兩種殘基對完整的抗HIV功能是必需的,。
這項研究增進了對A3F病毒顆粒衣殼化及抗病毒功能的機制的了解，也將會促進抑制HIV-1復(fù)制新策略的研究,。（生物谷Deepblue編譯）
doi: 10.1074/jbc.M111.310839
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Signals in APOBEC3F N-terminal and C-terminal Deaminase Domains Each Contribute to Encapsidation in HIV-1 Virions and Are Both Required for HIV-1 Restriction
Chisu Song, Lorraine Sutton, Megan E. Johnson, Richard T. D'Aquila and John P. Donahue.
Human cytidine deaminases APOBEC3F (A3F) and APOBEC3G (A3G) inhibit human immunodeficiency virus type-1 (HIV-1) replication.In the absence of HIV-1 Vif, A3F and/or A3G are incorporated into assembling virions and exert antiviral functions in subsequently infected target cells.Encapsidation of A3F or A3G within the protease-matured virion core following their incorporation into virions is hypothesized to be important for the antiviral function of these proteins. In this report, we demonstrated that A3F was quantitatively encapsidated in the mature virion core.In distinct contrast, A3G was distributed both within and outside of the virion core. Analysis of a series of A3F-A3G chimeras comprised of exchanged N- and C-terminal deaminase domains identified a 14 amino acid segment in the A3F C-terminal deaminase domain that contributed to preferential encapsidation and anti-HIV activity.Amino acid residue L306 in this C-terminal segment was determined to be necessary, but not sufficient, for these effects. Amino acid residue W126 in the N-terminal deaminase domain was determined also to contribute to preferential encapsidation and antiviral activity of A3F.Analysis of the A3F (W126A L306A) double mutant revealed that both residues are required for full anti-HIV function.The results reported here advance our understanding of the mechanisms of A3F virion encapsidation and antiviral function and may lead to innovative strategies to inhibit HIV-1 replication.
