Expanded tissue targets for foamy virus replication with simian immunodeficiency virus-induced immunosuppression
Expanded tissue targets for foamy virus replication with simian immunodeficiency virus-induced immunosuppression
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DOI：
10.1128/jvi.80.2.663-670.2006
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发表时间：
2006-01-01
影响因子：
5.4
通讯作者：
Linial, ML
中科院分区：
文献类型：
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作者：
Murray, SM;Picker, LJ;Linial, ML
泡沫病毒（FV）是已知最古老的逆转录病毒属，在非人灵长类动物中存在超过6000万年。FV可有效传播，导致终身非致病性感染。传播被认为是通过唾液发生的，但详细机制尚不清楚。有趣的是，这种持续感染与FV在体外引起的快速细胞病变形成对比，表明宿主对FV的防御。为了更好地了解FV复制的组织特异性和宿主对FV细胞病变的免疫防御，我们定量了健康恒河猴（RM）和那些严重免疫抑制的猴免疫缺陷病毒（SIV）的组织中的FV。与早期的研究结果相反，我们发现所有免疫活性动物的口腔组织中始终有高水平的病毒RNA，但在其他组织中没有检查，包括小肠。引人注目的是，在所有SIV感染的RM的小肠中检测到丰富的病毒转录物，这已被证明是SIV（和人类免疫缺陷病毒）诱导的CD4（+）T细胞耗竭的主要部位。相反，SIV感染动物口咽组织中的病毒RNA水平有降低的趋势。FV复制扩展到小肠，而不是其他CD4（+）T细胞耗尽的组织，表明T细胞耗尽以外的因素，如SIV感染后空肠微环境的失调，可能是FV复制扩展的组织嗜性的原因。
Foamy viruses (FV) are the oldest known genus of retroviruses and have persisted in nonhuman primates for over 60 million years. FV are efficiently transmitted, leading to a lifelong nonpathogenic infection. Transmission is thought to occur through saliva, but the detailed mechanism is unknown. Interestingly, this persistent infection contrasts with the rapid cytopathicity caused by FV in vitro, suggesting a host defense against FV. To better understand the tissue specificity of FV replication and host immunologic defense against FV cytopathicity, we quantified FV in tissues of healthy rhesus macaques (RM) and those severely immuno-suppressed by simian immunodeficiency virus (SIV). Contrary to earlier findings, we find that all immunocompetent animals consistently have high levels of viral RNA in oral tissues but not in other tissues examined, including the small intestine. Strikingly, abundant viral transcripts were detected in the small intestine of all of the SIV-infected RM, which has been shown to be a major site of SIV (and human immunodeficiency virus)-induced CD4(+) T-cell depletion. In contrast, there was a trend to lower viral RNA levels in oropharyngeal tissues of SIV-infected animals. The expansion of FV replication to the small intestine but not to other CD4(+) T-cell-depleted tissues suggests that factors other than T-cell depletion, such as dysregulation of the jejunal microenvironment after SIV infection, likely account for the expanded tissue tropism of FV replication.