Markazi Ashley, Meng Wen, Bracci Paige M, McGrath Michael S, Gao Shou-Jiang
Cancer Virology Program, UPMC Hillman Cancer Center, Pittsburgh, PA 15213, USA.
Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, PA 15219, USA.
Cancers (Basel). 2021 Aug 25;13(17):4269. doi: 10.3390/cancers13174269.
The objective of this article is to review the current status of the bacteria-virus interplay in Kaposi's sarcoma-associated herpesvirus (KSHV) infection and KSHV-driven cancers. KSHV is the etiological agent of several cancers, including Kaposi's sarcoma (KS) and primary effusion lymphoma. Due to immunosuppression, patients with KSHV are at an increased risk for bacterial infections. Moreover, among patients coinfected by HIV and KSHV, patients with KS have distinct oral microbiota compared to non-KS patients. Bacterial biomarkers associated with KSHV-driven cancers can provide insights in discerning the mechanisms of KSHV-induced oncogenesis. For example, pathogen-associated molecular patterns and bacterial products of certain bacterial species can regulate the expression of KSHV lytic and latent genes, thereby affecting viral replication and dissemination. In addition, infection with distinct opportunistic bacterial species have been associated with increased cell proliferation and tumorigenesis in KSHV-induced cancers through activation of pro-survival and -mitogenic cell signaling pathways. By elucidating the various mechanisms in which bacteria affect KSHV-associated pathogenesis, we will be able to pinpoint therapeutic targets for KSHV infection and KSHV-related cancers.
本文的目的是综述卡波西肉瘤相关疱疹病毒（KSHV）感染及KSHV驱动的癌症中细菌与病毒相互作用的现状。KSHV是包括卡波西肉瘤（KS）和原发性渗出性淋巴瘤在内的几种癌症的病原体。由于免疫抑制，KSHV患者发生细菌感染的风险增加。此外，在HIV和KSHV合并感染的患者中，KS患者与非KS患者相比，口腔微生物群有所不同。与KSHV驱动的癌症相关的细菌生物标志物可以为洞察KSHV诱导肿瘤发生的机制提供线索。例如，某些细菌物种的病原体相关分子模式和细菌产物可以调节KSHV裂解基因和潜伏基因的表达，从而影响病毒的复制和传播。此外，通过激活促生存和促有丝分裂细胞信号通路，感染不同的机会性细菌物种与KSHV诱导的癌症中细胞增殖和肿瘤发生增加有关。通过阐明细菌影响KSHV相关发病机制的各种机制，我们将能够确定KSHV感染和KSHV相关癌症的治疗靶点。
