Windisch Wolfram, Pieper Monika, Ziemele Inga, Rockstroh Jürgen, Brockmann Michael, Schildgen Oliver, Schildgen Verena
Department of Pneumology, Kliniken der Stadt Köln gGmbH, University of Witten/Herdecke, Cologne, Germany.
Institut für Pathologie, Klinikum der Privaten Universität Witten/Herdecke mit Sitz in Köln, Cologne , Germany.
JMM Case Rep. 2016 Aug 30;3(4):e005052. doi: 10.1099/jmmcr.0.005052. eCollection 2016 Aug.
The human bocavirus (HBoV) is a parvovirus and is associated with mild to life-threatening acute or persisting respiratory infections, frequently accompanied by further pathogens. So far, there is limited knowledge on the mechanisms of persistence, and no reports on chronic infections or latency have been published so far.
An immunocompetent male patient suffers from a chronic HBoV1 infection, i.e. viral DNA was detected in both serum and bronchoalveolar lavage (BAL) for >5 months without co-infections and with respiratory symptoms resolved spontaneously while receiving symptomatic treatment with montelukast and corticosteroids. Following the symptomatic medication of a chronic infection with HBoV1 viraemia indicating active viral replication lasting over 5 months, the patient cleared the viraemia and no further viral DNA was detectable in the BAL. However, by fluorescence hybridization analyses of mucosal biopsies, it was shown that the virus genome still persisted in the absence of viral shedding but in a more compact manner possibly representing a supercoiled episomal form of this otherwise linear single-stranded DNA genome. This indicated the entry into a latency phase. Moreover, the cytokine profile and the IP-10/TARC ratio, a marker for fibrotization, seem to have been altered by HBoV1 replication. Although specific IgG antibodies were detectable during the whole observation period, they showed an apparently insufficient neutralising activity.
On the one hand, these findings suggest that the symptomatic medication may have led to clearance of the virus from blood and airways and, moreover, that the viral DNA persists in the tissue as an altered episomal form favoured by lacking neutralising antibodies. This appears to be important in order to reduce possible long-term effects such as lung fibrosis.
人博卡病毒(HBoV)是一种细小病毒,与轻度至危及生命的急性或持续性呼吸道感染相关,常伴有其他病原体。到目前为止,关于病毒持续存在的机制了解有限,且尚无关于慢性感染或潜伏的报道。
一名免疫功能正常的男性患者患有慢性HBoV1感染,即在血清和支气管肺泡灌洗(BAL)中均检测到病毒DNA超过5个月,无合并感染,且在接受孟鲁司特和皮质类固醇对症治疗时呼吸道症状自行缓解。在对慢性HBoV1感染进行对症治疗后,病毒血症表明活跃的病毒复制持续超过5个月,患者清除了病毒血症,BAL中未检测到进一步的病毒DNA。然而,通过对黏膜活检组织的荧光杂交分析表明,病毒基因组在无病毒脱落的情况下仍持续存在,但以更紧密的方式存在,可能代表这种线性单链DNA基因组的超螺旋游离形式。这表明进入了潜伏阶段。此外,细胞因子谱以及纤维化标志物IP-10/TARC比值似乎因HBoV1复制而发生了改变。尽管在整个观察期内均可检测到特异性IgG抗体,但它们的中和活性明显不足。
一方面,这些发现表明对症治疗可能导致病毒从血液和气道中清除,此外,病毒DNA以游离形式持续存在于组织中,这种形式因缺乏中和抗体而更易形成。这对于减少可能的长期影响如肺纤维化似乎很重要。