Genomic diversity of HPV6 and HPV11 in recurrent respiratory papillomatosis: Association with malignant transformation in the lungs and clinical outcomes

IF 4.7 Q1 VIROLOGY
Massilva Rahmoun , Audrey Aussel , Sarah Bouzidi , Vincent Pedergnana , Victor Malassigné , Julien Puech , David Veyer , Hélène Péré , Charles Lepine , Fabian Blanc , Nathalie Boulle , Valérie Costes-Martineau , Ignacio G. Bravo
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Abstract

Recurrent respiratory papillomatosis (RRP) is a rare, proliferative disease caused by human papillomavirus 6 (HPV6) and HPV11. RRP can occasionally spread and undergo malignant transformation.
We analysed samples across time for five RRP patients with malignant transformation and four with highly recurrent, non-malignant RRP by applying high-throughput sequencing.
Patients with malignant transformation were infected by HPV11_A1/A2, while most non-malignant cases were associated with HPV6. Transient multiple infections with HPV6 and HPV11 were found in two patients, and resolved later to single infections. Viral genome loads were homogeneous across groups (median = 78 viral genomes per human genome). Within-patient, we did not observe differences between the viral sequences in the papillomatous lesions and in the malignant tissue. Genetic analysis of the NLRP1 gene revealed no known mutations linked to idiopathic RRP, though some novel variants merit to be explored in larger cohorts.
HPV11 infections appear associated with RRP malignant transformation in young patients. Multiple infections can occur in RRP, but within-patient viral diversity is minimal for a given genotype. Our results confirm the importance of viral genotype in disease prognosis and are consistent with growing evidence of HPV11 infections to be differentially associated with RRP malignant transformation in young patients.
复发性呼吸道乳头状瘤病中 HPV6 和 HPV11 的基因组多样性:与肺部恶性转化和临床结果的关系
复发性呼吸道乳头状瘤病(RRP)是一种罕见的增殖性疾病,由人类乳头状瘤病毒 6(HPV6)和 HPV11 引起。我们应用高通量测序技术分析了 5 名恶性转化 RRP 患者和 4 名高度复发性非恶性 RRP 患者的不同时期样本。在两名患者中发现了HPV6和HPV11的一过性多重感染,后来又转变为单一感染。各组的病毒基因组载量相同(中位数 = 每个人类基因组 78 个病毒基因组)。在患者内部,我们没有观察到乳头状瘤病变和恶性组织中病毒序列的差异。对 NLRP1 基因的遗传分析表明,没有发现与特发性 RRP 相关的已知变异,但一些新型变异值得在更大的群体中进行研究。RRP可发生多重感染,但对于特定基因型而言,患者体内的病毒多样性极少。我们的研究结果证实了病毒基因型在疾病预后中的重要性,而且越来越多的证据表明,HPV11感染与年轻患者的RRP恶性转化有不同程度的关联。
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来源期刊
Tumour Virus Research
Tumour Virus Research Medicine-Infectious Diseases
CiteScore
6.50
自引率
2.30%
发文量
16
审稿时长
56 days
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