Cornejo Castro Elena M, Marshall Vickie, Lack Justin, Lurain Kathryn, Immonen Taina, Labo Nazzarena, Fisher Nicholas C, Ramaswami Ramya, Polizzotto Mark N, Keele Brandon F, Yarchoan Robert, Uldrick Thomas S, Whitby Denise
Viral Oncology Section, AIDS and Cancer Virus Program, Frederick National Laboratory for Cancer Research, P.O. Box B, Frederick, MD 21702, USA.
Advanced Biomedical Computing Center, Leidos Biomedical Research, Inc., Frederick, MD 21702, USA.
Virus Evol. 2020 Jun 30;6(2):veaa047. doi: 10.1093/ve/veaa047. eCollection 2020 Jul.
Kaposi sarcoma herpesvirus (KSHV) is the etiological agent of three malignancies, Kaposi sarcoma (KS), primary effusion lymphoma (PEL) and KSHV-associated multicentric Castelman disease. KSHV infected patients may also have an interleukin six-related KSHV-associated inflammatory cytokine syndrome. KSHV-associated diseases occur in only a minority of chronically KSHV-infected individuals and often in the setting of immunosuppression. Mechanisms by which KSHV genomic variations and systemic co-infections may affect the pathogenic pathways potentially leading to these diseases have not been well characterized . To date, the majority of comparative genetic analyses of KSHV have been focused on a few regions scattered across the viral genome. We used next-generation sequencing techniques to investigate the taxonomic groupings of viruses from malignant effusion samples from fourteen participants with advanced KSHV-related malignancies, including twelve with PEL and two with KS and elevated KSHV viral load in effusions. The genomic diversity and evolutionary characteristics of nine isolated, near full-length KSHV genomes revealed extensive evidence of mosaic patterns across all these genomes. Further, our comprehensive NGS analysis allowed the identification of two distinct KSHV genome sequences in one individual, consistent with a dual infection. Overall, our results provide significant evidence for the contribution of KSHV phylogenomics to the origin of KSHV subtypes. This report points to a wider scope of studies to establish genome-wide patterns of sequence diversity and define the possible pathogenic role of sequence variations in KSHV-infected individuals.
卡波西肉瘤疱疹病毒（KSHV）是三种恶性肿瘤的病原体，即卡波西肉瘤（KS）、原发性渗出性淋巴瘤（PEL）和KSHV相关的多中心Castleman病。KSHV感染患者也可能患有与白细胞介素6相关的KSHV相关炎性细胞因子综合征。KSHV相关疾病仅发生在少数长期感染KSHV的个体中，且通常发生在免疫抑制的情况下。KSHV基因组变异和全身性合并感染可能影响潜在导致这些疾病的致病途径的机制尚未得到充分表征。迄今为止，大多数KSHV的比较遗传分析都集中在病毒基因组中分散的几个区域。我们使用下一代测序技术研究了14名患有晚期KSHV相关恶性肿瘤的参与者的恶性渗出液样本中的病毒分类群，其中包括12名患有PEL的患者和2名患有KS且渗出液中KSHV病毒载量升高的患者。9个分离的、近乎全长的KSHV基因组的基因组多样性和进化特征揭示了所有这些基因组中广泛存在的镶嵌模式证据。此外，我们全面的NGS分析在一个个体中鉴定出两种不同的KSHV基因组序列，这与双重感染一致。总体而言，我们的结果为KSHV系统发育基因组学对KSHV亚型起源的贡献提供了重要证据。本报告指出需要进行更广泛的研究，以建立全基因组的序列多样性模式，并确定序列变异在KSHV感染个体中可能的致病作用。
