最近发表的来自喀麦隆卡波西肉瘤病例对照研究的近全长 KSHV 基因组显示了病毒重组和混合感染的有力证据，但没有与疾病相关的序列变异。使用相同的方法，对来自 76 名患有 KSHV 相关疾病的个体的另外 102 个 KSHV 基因组进行了测序。诊断包括所有 KSHV 相关疾病 (KAD)：卡波西肉瘤 (KS)、原发性渗出性淋巴瘤 (PEL)、KSHV 相关大细胞淋巴瘤 (KSHV-LCL)、一种多中心 Castleman 病 (KSHV-MCD) 和 KSHV炎症细胞因子综合征（KICS）。参与者来自 22 个不同的国家，为获得各种 KSHV 基因组的新的近全长序列提供了机会。其中包括 KSHV K1 亚型 A、B、C 和 F 以及 E 亚型的基因组近全长序列，此前尚未获得这些基因组的完整序列。观察到高水平的重组。十四个人 (18%) 显示出感染多种 KSHV 变体（来自两到四个独特基因组）的证据。对从同一参与者的不同采样点（包括 PBMC、组织活检、口腔液和积液）获得的序列进行了 26 次比较，确定了不同生物区室之间接近完整的基因组保守性。在编码区和非编码区中鉴定出了多态性，包括 K3 和 K15 基因中的插入缺失以及本文首次报道的序列倒置。 KSHV ORF46 中的一个此类多态性（针对 KSHV K1 亚型 E2）编码了尿嘧啶 DNA 糖基化酶的亮氨酸环延伸中的突变，导致该蛋白质的生化功能发生改变。这证实了 KSHV 序列变异可能产生功能性后果，值得进一步研究。这项研究代表了迄今为止对 KAD 个体中 KSHV 基因组序列进行的最大规模、最多样化的分析，并提供了有关全球 KSHV 基因组学的重要新信息。版权：这是一篇开放获取文章，没有任何版权，可以自由复制、分发、传输、修改、构建或由任何人出于任何合法目的以其他方式使用。该作品在知识共享 CC0 公共领域奉献下提供。

Recently published near full-length KSHV genomes from a Cameroon Kaposi sarcoma case-control study showed strong evidence of viral recombination and mixed infections, but no sequence variations associated with disease. Using the same methodology, an additional 102 KSHV genomes from 76 individuals with KSHV-associated diseases have been sequenced. Diagnoses comprise all KSHV-associated diseases (KAD): Kaposi sarcoma (KS), primary effusion lymphoma (PEL), KSHV-associated large cell lymphoma (KSHV-LCL), a type of multicentric Castleman disease (KSHV-MCD), and KSHV inflammatory cytokine syndrome (KICS). Participants originated from 22 different countries, providing the opportunity to obtain new near full-length sequences of a wide diversity of KSHV genomes. These include near full-length sequence of genomes with KSHV K1 subtypes A, B, C, and F as well as subtype E, for which no full sequence was previously available. High levels of recombination were observed. Fourteen individuals (18%) showed evidence of infection with multiple KSHV variants (from two to four unique genomes). Twenty-six comparisons of sequences, obtained from various sampling sites including PBMC, tissue biopsies, oral fluids, and effusions in the same participants, identified near complete genome conservation between different biological compartments. Polymorphisms were identified in coding and non-coding regions, including indels in the K3 and K15 genes and sequence inversions here reported for the first time. One such polymorphism in KSHV ORF46, specific to the KSHV K1 subtype E2, encoded a mutation in the leucine loop extension of the uracil DNA glycosylase that results in alteration of biochemical functions of this protein. This confirms that KSHV sequence variations can have functional consequences warranting further investigation. This study represents the largest and most diverse analysis of KSHV genome sequences to date among individuals with KAD and provides important new information on global KSHV genomics.Copyright: This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.