Ornelles David A, Gooding Linda R, Garnett-Benson C
Department of Microbiology and Immunology, Wake Forest School of Medicine, Winston-Salem, North Carolina, United States of America.
Emory University School of Medicine, Department of Microbiology and Immunology, Atlanta, Georgia, United States of America.
PLoS One. 2015 Mar 12;10(3):e0119256. doi: 10.1371/journal.pone.0119256. eCollection 2015.
Credible but conflicting reports address the frequency of prenatal infection by species C adenovirus. This question is important because these viruses persist in lymphoid cells and suppress double-stranded DNA-break repair. Consequently, prenatal adenovirus infections may generate the aberrant clones of lymphocytes that precede development of childhood acute lymphoblastic leukemia (ALL). The present study was designed to overcome technical limitations of prior work by processing cord blood lymphocytes within a day of collection, and by analyzing sufficient numbers of lymphocytes to detect adenovirus-containing cells at the lower limits determined by our previous studies of tonsil lymphocytes. By this approach, adenoviral DNA was identified in 19 of 517 (3.7%) samples, providing definitive evidence for the occurrence of prenatal infection with species C adenoviruses in a significant fraction of neonates predominantly of African American and Hispanic ancestry. Cord blood samples were also tested for the presence of the ETV6-RUNX1 translocation, the most common genetic abnormality in childhood ALL. Using a nested PCR assay, the ETV6-RUNX1 transcript was detected in four of 196 adenovirus-negative samples and one of 14 adenovirus-positive cord blood samples. These findings indicate that this method will be suitable for determining concordance between adenovirus infection and the leukemia-associated translocations in newborns.
关于C型腺病毒产前感染的频率，有可靠但相互矛盾的报道。这个问题很重要，因为这些病毒会在淋巴细胞中持续存在并抑制双链DNA断裂修复。因此，产前腺病毒感染可能会产生在儿童急性淋巴细胞白血病（ALL）发生之前的异常淋巴细胞克隆。本研究旨在克服先前研究的技术局限性，方法是在采集脐带血淋巴细胞的当天进行处理，并分析足够数量的淋巴细胞，以检测出我们之前对扁桃体淋巴细胞研究确定的下限水平的含腺病毒细胞。通过这种方法，在517个样本中的19个（3.7%）中鉴定出腺病毒DNA，这为相当一部分主要为非裔美国人和西班牙裔血统的新生儿发生C型腺病毒产前感染提供了确凿证据。还对脐带血样本进行了ETV6-RUNX1易位检测，这是儿童ALL中最常见的基因异常。使用巢式PCR检测法，在196个腺病毒阴性样本中的4个以及14个腺病毒阳性脐带血样本中的1个中检测到了ETV6-RUNX1转录本。这些发现表明，该方法将适用于确定新生儿腺病毒感染与白血病相关易位之间的一致性。
