The restriction of zoonotic PERV transmission by human APOBEC3G.
The restriction of zoonotic PERV transmission by human APOBEC3G.
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DOI：
10.1371/journal.pone.0000893
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发表时间：
2007-09-12
期刊：
影响因子：
3.7
通讯作者：
Harris RS
中科院分区：
文献类型：
--
作者：
Jónsson SR;LaRue RS;Stenglein MD;Fahrenkrug SC;Andrésdóttir V;Harris RS
人APOBEC3G蛋白是一种先天性抗病毒因子，可以显著抑制一些内源性和外源性逆转录病毒的复制。有目的地利用这种抗病毒防御的前景正在调查中。在此，长期共培养实验用于显示通过在产病毒的猪肾细胞中表达人APOBEC3G，猪内源性逆转录病毒（PERV）从猪到人细胞的传播降低至几乎不可检测的水平。抑制发生脱氨独立的机制，可能在颗粒生产后，但之前的病毒可以通过整合到人类基因组DNA永生化。PERV抑制不需要APOBEC3G的DNA胞嘧啶脱氨酶活性，相应地，未检测到APOBEC3G可归因的超突变。相反，猪的唯一内源性APOBEC3蛋白的过表达未能显著干扰PERV传播。总之，这些数据构成了APOBEC3蛋白可用于加强细胞的先天抗病毒防御以防止内源性逆转录病毒的人畜共患病传播的第一个原理证明。这些研究表明，人APOBEC3G转基因猪将提供更安全，PERV较少的异种移植资源，类似的跨物种APOBEC3依赖性限制策略可能有助于阻止其他内源性和外源性逆转录病毒感染。
The human APOBEC3G protein is an innate anti-viral factor that can dominantly inhibit the replication of some endogenous and exogenous retroviruses. The prospects of purposefully harnessing such an anti-viral defense are under investigation. Here, long-term co-culture experiments were used to show that porcine endogenous retrovirus (PERV) transmission from pig to human cells is reduced to nearly undetectable levels by expressing human APOBEC3G in virus-producing pig kidney cells. Inhibition occurred by a deamination-independent mechanism, likely after particle production but before the virus could immortalize by integration into human genomic DNA. PERV inhibition did not require the DNA cytosine deaminase activity of APOBEC3G and, correspondingly, APOBEC3G-attributable hypermutations were not detected. In contrast, over-expression of the sole endogenous APOBEC3 protein of pigs failed to interfere significantly with PERV transmission. Together, these data constitute the first proof-of-principle demonstration that APOBEC3 proteins can be used to fortify the innate anti-viral defenses of cells to prevent the zoonotic transmission of an endogenous retrovirus. These studies suggest that human APOBEC3G-transgenic pigs will provide safer, PERV-less xenotransplantation resources and that analogous cross-species APOBEC3-dependent restriction strategies may be useful for thwarting other endogenous as well as exogenous retrovirus infections.
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影响因子：
14.9
作者：
Jonsson, Stefan R.;Hache, Guylaine;Stenglein, Mark D.;Fahrenkrug, Scott C.;Andresdottir, Valgerdur;Harris, Reuben S.
通讯作者：
Harris, Reuben S.
影响因子：
64.5
作者：
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通讯作者：
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影响因子：
64.8
作者：
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通讯作者：
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影响因子：
9.2
作者：
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通讯作者：
Uchiyama, Takashi
影响因子：
64.8
作者：
Gao, F;Bailes, E;Hahn, BH
通讯作者：
Hahn, BH