Persistent systemic rotavirus vaccine infection in a child with X-linked severe combined immunodeficiency.
Persistent systemic rotavirus vaccine infection in a child with X-linked severe combined immunodeficiency.
复制标题
X 连锁严重联合免疫缺陷儿童持续全身性轮状病毒疫苗感染。
DOI：
10.1002/jmv.25410
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发表时间：
2019
期刊：
影响因子：
--
通讯作者：
Ariga T.
中科院分区：
文献类型：
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作者：
Yoshikawa T;Ihira M;Higashimoto Y;Hattori F;Miura H;Sugata K;Komoto S;Taniguchi K;Iguchi A;Yamada M;Ariga T.
目的了解系统性A组轮状病毒(RVA)感染情况，了解X连锁重症联合免疫缺陷(SCID)患者持续病毒的基因变化。方法采用轮状Teq疫苗(RV5)基因特异性实时逆转录聚合酶链式反应(RT-PCR)检测连续采集的血清和粪便标本中的病毒RNA载量。下一代序列分析通过对11个基因片段进行测序来确定病毒的基因分型。用聚丙烯酰胺凝胶电泳法(PAGE)检测病毒基因重排。结果一名7个月大的男婴在第三次注射RV5后出现慢性腹泻，并无法发育。他被诊断出患有X连锁SCID，并成功接受了脐带血移植。在连续采集的粪便和血清标本中检测到高拷贝数的RV5型G1RNA，病毒RNA载量的动态变化与临床疾病的严重程度有关。下一代序列分析显示，在疫苗衍生的轮状病毒株中，VP7基因和VP4基因至少在WI79-9/G1P7[5]和WI79-4/G6P1A[8]之间发生了遗传重排。PAGE分析提示多个基因发生基因重排，序列分析证实NSP5基因存在基因重排。结论血清和粪便标本中RVA RNA载量的动态变化与患者的临床病程一致。在RV5疫苗的五种基因型中，G1基因型在该患者中复制良好。在持续感染的RV5的G1型中显示了重排和重排。
ObjectiveThe main aims of the present study were to elucidate the systemic group A rotavirus (RVA) infection and to clarify the genetic changes of persistent virus in the X‐linked severe combined immunodeficiency (SCID) patient.MethodsRotaTeq vaccine (RV5) genotype‐specific real‐time reverse transcription polymerase chain reaction was used to monitor viral RNA load in serially collected serum and stool samples. Next‐generation sequence analysis was used to determine the genotype of the virus by sequencing 11 gene segments. Polyacrylamide gel electrophoresis (PAGE) analysis was used to identify rearrangement of viral genes. The gene rearrangement was examined in NSP5 gene by using Sanger sequence.ResultsA 7‐month‐old boy demonstrated chronic diarrhea following the third administration of RV5 and failure to thrive. He was diagnosed with X‐linked SCID and successfully underwent cord blood transplantation. High copy numbers of RV5 genotype G1 RNA were detected in serially collected stool and serum samples and the kinetics of viral RNA loads were correlated with the degree of clinical disease. Next‐generation sequence analysis revealed genetic reassortment at least between the strains WI79‐9/G1P7[5] and WI79‐4/G6P1A[8] in the VP7 gene and the VP4 gene among the vaccine‐derived rotavirus strains. In addition, PAGE analysis suggested genetic rearrangements in several genes, and it was confirmed in the NSP5 gene by sequence analysis.ConclusionsThe kinetics of RVA RNA load in serum and stool samples was consistent with the clinical course of the patient. Among five genotypes of RV5 vaccine, G1 genotype replicated well in this patient. Reassortment and rearrangements were demonstrated in persistently infected G1 genotype of RV5.