Cecchini Sylvain, Negrete Alejandro, Virag Tamas, Graham Barney S, Cohen Jeffrey I, Kotin Robert M
Laboratory of Biochemical Genetics, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
Clin Vaccine Immunol. 2009 May;16(5):597-604. doi: 10.1128/CVI.00470-08. Epub 2009 Feb 25.
Recently, molecular screening for pathogenic agents has identified a partial genome of a novel parvovirus, called human bocavirus (HBoV). The presence of this newly described parvovirus correlated with upper and lower respiratory tract infections in children. Lower respiratory tract infections are a leading cause of hospital admission in children, and the etiological agent has not been identified in up to 39% of these cases. Using baculovirus expression vectors (BEVs) and an insect cell system, we produced virus-like particles (VLPs) of HBoV. The engineered BEVs express the HBoV capsid proteins stoichiometrically from a single open reading frame. Three capsid proteins assemble into the VLP rather than two proteins predicted from the HBoV genome sequence. The denatured capsid proteins VP1, VP2, and VP3 resolve on silver-stained sodium dodecyl sulfate-polyacrylamide gels as three bands with apparent molecular masses of 72 kDa, 68 kDa, and 62 kDa, respectively. VP2 apparently initiates at a GCT codon (alanine) 273 nucleotides downstream from the VP1 start site and 114 nucleotides upstream from the VP3 initiation site. We characterized the stable capsids using physical, biochemical, and serological techniques. We found that the density of the VLP is 1.32 g/cm(3) and is consistent with an icosahedral symmetry with approximately a 25-nm diameter. Rabbit antiserum against the capsid of HBoV, which did not cross-react with adeno-associated virus type 2, was used to develop enzyme-linked immunosorbent assays (ELISAs) for anti-HBoV antibodies in human serum. Using ELISA, we tested 404 human serum samples and established a range of antibody titers in a large U.S. adult population sample.
最近,对病原体的分子筛查鉴定出一种新型细小病毒的部分基因组,称为人博卡病毒(HBoV)。这种新描述的细小病毒的存在与儿童上、下呼吸道感染相关。下呼吸道感染是儿童住院的主要原因,在高达39%的此类病例中尚未确定病原体。我们使用杆状病毒表达载体(BEV)和昆虫细胞系统生产了HBoV病毒样颗粒(VLP)。工程化的BEV从单个开放阅读框以化学计量方式表达HBoV衣壳蛋白。三种衣壳蛋白组装成VLP,而不是根据HBoV基因组序列预测的两种蛋白。变性的衣壳蛋白VP1、VP2和VP3在银染的十二烷基硫酸钠-聚丙烯酰胺凝胶上分别以三条带的形式出现,表观分子量分别为72 kDa、68 kDa和62 kDa。VP2显然从VP1起始位点下游273个核苷酸和VP3起始位点上游114个核苷酸处的GCT密码子(丙氨酸)开始。我们使用物理、生化和血清学技术对稳定的衣壳进行了表征。我们发现VLP的密度为1.32 g/cm³,与直径约为25 nm的二十面体对称性一致。针对HBoV衣壳的兔抗血清不与2型腺相关病毒发生交叉反应,用于开发检测人血清中抗HBoV抗体的酶联免疫吸附测定(ELISA)。我们使用ELISA检测了404份人血清样本,并在一大群美国成年人样本中确定了一系列抗体滴度。