Persistent zoonotic infection of a human with simian foamy virus in the absence of an intact orf-2 accessory gene
Persistent zoonotic infection of a human with simian foamy virus in the absence of an intact orf-2 accessory gene
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DOI：
10.1128/jvi.73.11.9619-9624.1999
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发表时间：
1999-11-01
影响因子：
5.4
通讯作者：
Sandstrom, PA
中科院分区：
文献类型：
--
作者：
Callahan, ME;Switzer, WM;Sandstrom, PA
虽然泡沫病毒（FV）在非人灵长类动物中流行，但FV在人类中的感染是罕见的。最近，在231名职业暴露于灵长类动物的个体中有4人（1.8%）报告了猴泡沫病毒（SFV）感染。还没有发现配偶的继发性传播，这表明虽然FV容易人畜共患，但人类可能是死端宿主。在不同的猿种中，SFV在长末端重复序列（LTR）和3'辅助开放阅读框（ORF）的U3区域内表现出显著的序列多样性。为了研究持续的人SFV感染和明显缺乏二次传播是否与FV调控区的遗传适应相关，我们对来自非洲绿色猴源SFV感染的人（SFV-3）的组织培养分离株和外周血单核细胞样品进行了LTR、内部启动子、ORF-1和ORF-2的序列分析。与原型SFV-3序列相比，LTR、内部启动子和FV反式激活因子（ORF-1）显示序列保守性，表明FV人畜共患病不依赖于宿主对这些转录重要区域的特异性适应。然而，ORF-2含有许多有害的突变，预测会导致蛋白质合成的过早终止。ORF-2部分编码60-kDa Bet融合蛋白，建议参与持续细胞SFV感染的建立。这些结果表明，持续的人类感染SFV和降低的传播性可能是由一个功能ORF-2的情况下的影响。
Although foamy viruses (FVs) are endemic among nonhuman primates, FV infection among humans is rare. Recently, simian foamy virus (SFV) infection was reported in 4 of 231 individuals occupationally exposed to primates (1.8%). Secondary transmission to spouses has not been seen, suggesting that while FV is readily zoonotic, humans may represent dead-end hosts. Among different simian species, SFV demonstrates significant sequence diversity within the U3 region of the long terminal repeat (LTR) and 3' accessory open reading frames (ORFs). To examine if persistent human SFV infection and apparent lack of secondary transmission are associated with genetic adaptations in FV regulatory regions, we conducted sequence analysis of the LTR, internal promoter, ORF-1, and ORF-2 on a tissue culture isolate and peripheral blood mononuclear cell samples from a human infected with SFV of African green monkey origin (SFV-3). Compared to the prototype SFV-3 sequence, the LTR, internal promoter, and FV transactivator (ORF-1) showed sequence conservation, suggesting that FV zoonosis is not dependent on host-specific adaptation to these transcriptionally important regions. However, ORF-2 contains a number of deleterious mutations predicted to result in premature termination of protein synthesis. ORF-2 codes in part for the 60-kDa Bet fusion protein, proposed to be involved in the establishment of persistent cellular SFV infections. These results suggest that persistent human infection by SFV and reduced transmissibility may be influenced by the absence of a functional ORF-2.