探討細小病毒科病毒殼體蛋白獨立區域對OVA致敏氣喘小鼠的影響

文獻已知感染呼吸道病毒可能會使呼吸道細胞型態改變並增加後天罹患氣喘的風險，而病毒感染也可能引起急性氣喘發作。人類微小病毒（Human parvovirus B19, B19V）與人類博卡病毒（Human bocavirus, HBoV）是細小病毒科中會導致人類疾病的兩株病毒，兩者皆由結構蛋白VP1及VP2組裝病毒殼體，其中VP1與VP2序列重疊，但VP1的N端較VP2多出一段胺基酸序列，稱為結構蛋白獨立區域（VP1 unique region, VP1u）。B19V的結構蛋白獨立區域含有227個胺基酸，稱為B19V-VP1u。HBoV的結構蛋白獨立區域含有129個胺基酸，稱為HBoV-VP1u。先前研究已知HBoV-VP1u與B19V-VP1u具有類似磷脂質分解酶A2（phospholipase-A2, PLA2）的motif以及分泌型磷脂質分解酶（sPLA2）的活性，當病毒感染宿主細胞時VP1u會裸露在殼體外部，並且對於病毒成功入侵宿主細胞引起細胞發炎反應，扮演非常重要的角色。由於B19V及HBoV病毒可透過呼吸道感染並且與呼吸道疾病的風險息息相關，因此本研究利用OVA致敏氣喘小鼠，探討B19V及HBoV病毒VP1u對呼吸道的影響。研究結果顯示HBoV-VP1u與B19V-VP1u能使小鼠呼吸道阻力增加; 血清IgE、IgG1濃度上升、IgG2a濃度下降；支氣管肺泡灌洗液淋巴球、嗜中性球與漿細胞增生、發炎指標MMP9與MMP2活性上升; 肺臟淋巴球浸潤增加等。綜合以上結果首次發現HBoV-VP1u與B19V-VP1u能加劇氣喘小鼠呼吸道過敏的情形。因此，細小病毒的結構蛋白獨立區域對於病毒的致病能力具有舉足輕重的角色。

It is known that the respiratory virus infection brings about airway remodeling and is associated with increased risks for asthma. Moreover, the infection may lead to asthma exacerbation. Human parvovirus B19 (B19V) and HBoV (Human bocavirus, HBoV) are classified as Parvoviridae family and known to be pathologic in humans. The virus capsid is composed of two structural proteins, VP1 and VP2, which are encoded by overlapping reading frames except for an identical region at the amino-terminal end of the VP1 protein, commonly referred to as the VP1-unique region (VP1u). In comparison with the VP1u re-gion of B19V contains 227 amino acids, called B19V-VP1u, HBoV contains 129 amino acids, called HBoV-VP1u. According to previous studies, the phospholipase A2 (PLA2)-like motif of HBoV-VP1u and B19V-VP1u had been identified and demonstrated to have secretory-PLA2 (sPLA2) activity. The exposure of HBoV-VP1u and B19V-VP1u during the entry plays a pivotal role of virus infection, and initiates a series of cellular in-flammatory responses. As B19V and HBoV are transmitted via respiratory tracts and closely related to respiratory diseases, we use an ovalbumin (OVA)-induced murine model of asthma to investigate the influence of HBoV-VP1u and B19V-VP1u on respiratory tracts. The results indicated that both HBoV-VP1u and B19V-VP1u resulted in an increase in Penh and serum IgE, IgG1, which in contrast with a decrease of IgG2a concentration. Lymphocytes, neutrophils, plasmocytes proliferation and increased MMP9, MMP2 activity were detected in bronchoalveolar lavage fluid. Furthermore, lymphocytes infiltrations in trachea were observed. All together, the study first discovers HBoV-VP1u and B19V-VP1u aggravate respiratory tract hypersensitivity. In consequence, both HBoV and B19V infection are associated with chronic respiratory disease, and the VP1-unique region of virus plays an important role of the virus virulence.