Latent Species C Adenoviruses in Human Tonsil Tissues
Latent Species C Adenoviruses in Human Tonsil Tissues
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DOI：
10.1128/jvi.02392-08
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发表时间：
2009-03-15
影响因子：
5.4
通讯作者：
Gooding, L. R.
中科院分区：
文献类型：
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作者：
Garnett, C. T.;Talekar, G.;Gooding, L. R.
虽然C种人类腺病毒建立持续感染，这种生活方式的分子细节仍然知之甚少。我们以前报道过腺病毒DNA以非感染性形式存在于人粘膜T淋巴细胞中（C。T. Garnett，D. Erdman，W. Xu和L. R. Gooding，J. Virol. 76：10608-10616，2002）。在这项研究中，人扁桃体和腺样体组织进行了分析，以确定感染的动力学，清除病毒DNA的速度，以及从这些组织中重新激活病毒的可能性。病毒DNA的存在在4岁时达到高峰，此后下降。病毒基因组的平均数量随着捐赠者的年龄而下降。病毒携带细胞的频率范围为3 × 10 - 7至3.4 × 10 - 4，而每个细胞的病毒DNA量变化较小，平均为280个拷贝。在这些组织中代表了所有种属C血清型，尽管腺病毒6型非常罕见。感染性病毒很少被检测到（94名受试者中有13名），即使在腺病毒DNA水平最高的供体中也是如此。在未培养的淋巴细胞中很少检测到腺病毒转录物（12个供体中的2个），但在刺激和培养后出现（13个供体中的11个）。在大多数供体样本中，淋巴细胞刺激培养可刺激病毒DNA复制。在体外刺激后，在15个供体中的13个中检测到新的感染性病毒。这些数据表明，C种腺病毒可以在粘膜淋巴细胞中建立潜伏感染，并且这些细胞的刺激可以引起病毒再活化，导致RNA转录、DNA复制和感染性病毒产生。
Although species C human adenoviruses establish persistent infections, the molecular details of this lifestyle remain poorly understood. We previously reported that adenovirus DNA is found in human mucosal T lymphocytes in a noninfectious form (C. T. Garnett, D. Erdman, W. Xu, and L. R. Gooding, J. Virol. 76: 10608-10616, 2002). In this study, human tonsil and adenoid tissues were analyzed to determine the dynamics of infection, the rate of clearance of viral DNA, and the possibility of reactivation of virus from these tissues. The presence of viral DNA peaked at 4 years of age and declined thereafter. The average number of viral genomes declined with the age of the donor. The frequency of virus-bearing cells ranged from 3 x 10(-7) to 3.4 x 10(-4), while the amount of viral DNA per cell varied less, with an average of 280 copies per cell. All species C serotypes were represented in these tissues, although adenovirus type 6 was notably rare. Infectious virus was detected infrequently (13 of 94 of donors tested), even among donors with the highest levels of adenoviral DNA. Adenovirus transcripts were rarely detected in uncultured lymphocytes (2 of 12 donors) but appeared following stimulation and culture (11 of 13 donors). Viral DNA replication could be stimulated in most donor samples by lymphocyte stimulation in culture. New infectious virus was detected in 13 of 15 donors following in vitro stimulation. These data suggest that species C adenoviruses can establish latent infections in mucosal lymphocytes and that stimulation of these cells can cause viral reactivation resulting in RNA transcription, DNA replication, and infectious virus production.