Schwarze Jurgen, O'Donnell Diarmund R, Rohwedder Angela, Openshaw Peter J M
Children's Clinic, St. Joseg-Hospital, Department of Medical Microbiology and Virology, Ruhr-Universität Bochum, Germany.
Am J Respir Crit Care Med. 2004 Apr 1;169(7):801-5. doi: 10.1164/rccm.200308-1203OC. Epub 2004 Jan 23.
Respiratory syncytial virus (RSV) causes bronchiolitis in infants, which is associated with recurrent wheezing in later childhood. There is mounting evidence that the virus becomes latent or persists in vivo, but little is known about the mechanisms of its latency, persistence, and immune evasion. We therefore infected BALB/c mice intranasally with human RSV, analyzed sequential tissue samples by direct culture and polymerase chain reaction for viral and messenger RNA, and monitored antiviral immune responses. Virus could not be detected in bronchoalveolar lavage samples beyond Day 14, but viral genomic and messenger RNA was present in lung homogenates for 100 days or more; combined depletion of CD4 and CD8 T cells allowed infective virus to be recovered. Neutralizing antibody and memory cytotoxic T cell responses were intact in mice with latent infections, and latent viral genome contained an authentic nonmutated M2 82-91 K(d) cytotoxic T lymphocyte epitope. A mutation of this epitope, detected in one clone, did not assist evasion. We suggest that RSV latency depends on persistence in privileged sites rather than on viral mutation.
呼吸道合胞病毒（RSV）可导致婴儿患细支气管炎，这与儿童后期反复喘息有关。越来越多的证据表明，该病毒会在体内潜伏或持续存在，但对其潜伏、持续存在及免疫逃逸机制知之甚少。因此，我们通过鼻内接种的方式用人类RSV感染BALB/c小鼠，通过直接培养和聚合酶链反应分析连续的组织样本中的病毒和信使RNA，并监测抗病毒免疫反应。在第14天之后，支气管肺泡灌洗样本中未检测到病毒，但病毒基因组和信使RNA在肺匀浆中存在100天或更长时间；联合去除CD4和CD8 T细胞可使感染性病毒得以恢复。潜伏感染小鼠的中和抗体和记忆性细胞毒性T细胞反应完好无损，潜伏病毒基因组包含一个真实的未突变的M2 82-91 K(d)细胞毒性T淋巴细胞表位。在一个克隆中检测到该表位的一个突变，但这并未有助于免疫逃逸。我们认为，RSV潜伏取决于在特定部位的持续存在，而非病毒突变。
