Moorad Razia, Peng Alice, Landis Justin, Pluta Linda J, Cano Patricio, Juarez Angelica, Dittmer Dirk P
Lineberger Comprehensive Cancer Center and Department of Microbiology and Immunology, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
J Virol. 2025 May 20;99(5):e0195024. doi: 10.1128/jvi.01950-24. Epub 2025 Apr 16.
Kaposi sarcoma (KS) is the most common cancer in people living with HIV (PLWH), particularly in sub-Saharan Africa (SSA), where Kaposi sarcoma herpesvirus (KSHV or human herpesvirus 8 [HHV-8]) is endemic. In KSHV endemic areas, the overall survival of KS patients has changed little over the past 20 years. A phylogenetic analysis of available full-length viral genomes ( = 164) identified two different virus lineages that co-circulate in KSHV endemic regions today. Their sequences differ from the GenBank reference sequence and those of common laboratory strains, which originated in the 1990s in the US and Europe. Targeted short-read sequencing accuracy was validated by PacBio-based long-read sequencing to resolve repeats. This analysis identified over 1,000 single nucleotide variants (SNV) in a new 14-member sequence collection from tumor biopsies and blood in Malawi with 127 ± 32 (median ± SD) SNV per genome. Most were private, i.e., specific to one individual's virus. Within each of the two lineages, KSHV continues to evolve over time and across national borders by genetic drift and recombination. Analyses of shared SNVs by AlphaFold2 predicted some changes in the conformation of key viral proteins. These findings may help our understanding of herpesvirus evolution.
To understand viruses, the field needs to know their genetic makeup. To develop mechanistic models, targeted therapies, and vaccines, we need comprehensive and up-to-date sequence information on the viral strains that circulate where the diseases appear today. Our knowledge of Kaposi sarcoma herpesvirus (KSHV) sequence distribution and evolution is behind that of other human herpesviruses and RNA viruses. Here, we add to community knowledge using new technologies and artificial intelligence.
卡波西肉瘤（KS）是艾滋病毒感染者（PLWH）中最常见的癌症，尤其是在撒哈拉以南非洲（SSA），卡波西肉瘤疱疹病毒（KSHV或人类疱疹病毒8 [HHV-8]）在那里流行。在KSHV流行地区，KS患者的总体生存率在过去20年中变化不大。对现有的全长病毒基因组（n = 164）进行系统发育分析，确定了两种不同的病毒谱系，它们如今在KSHV流行地区共同传播。它们的序列与GenBank参考序列以及源自20世纪90年代美国和欧洲的常见实验室菌株的序列不同。通过基于PacBio的长读长测序验证了靶向短读长测序的准确性，以解析重复序列。该分析在来自马拉维肿瘤活检和血液的一个新的14个成员的序列集合中鉴定出1000多个单核苷酸变异（SNV），每个基因组有127±32（中位数±标准差）个SNV。大多数是私有的，即特定于个体的病毒。在这两个谱系中的每一个谱系内，KSHV继续通过基因漂移和重组随时间和跨越国界而进化。通过AlphaFold2对共享SNV的分析预测了关键病毒蛋白构象的一些变化。这些发现可能有助于我们理解疱疹病毒的进化。
为了了解病毒，该领域需要知道它们的基因组成。为了开发机制模型、靶向疗法和疫苗，我们需要有关当今疾病出现地区流行的病毒株的全面和最新的序列信息。我们对卡波西肉瘤疱疹病毒（KSHV）序列分布和进化的了解落后于其他人类疱疹病毒和RNA病毒。在这里，我们使用新技术和人工智能增加了社区知识。
