Chen Jungang, Fan Jiaojiao, Malaviarachchi Priyangi A, Post Steven R, Lin Zhen, Zhang Xuming, Qin Zhiqiang
Department of Pathology, Winthrop P. Rockefeller Cancer Institute, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA.
Department of Microbiology and Immunology, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA.
J Med Virol. 2025 Jan;97(1):e70149. doi: 10.1002/jmv.70149.
An outbreak of the novel coronavirus SARS-CoV-2, the causative agent of COVID-19 pandemic, has resulted in over 7 million confirmed deaths. In addition to severe respiratory and systematic symptoms, several comorbidities increase the risk of fatal outcomes. Therefore, it is essential to investigate the impact of COVID-19 on pre-existing conditions in patients, such as cancer and other infectious diseases. Recent clinical studies have reported the reactivation of human herpesviruses, including Kaposi's sarcoma-associated herpesvirus (KSHV), in severe COVID-19 patients or vaccinated individuals. To support these clinical observations, we established a KSHV/SARS-CoV-2 co-infection system in A549-hACE2 cells. Our findings indicate that co-infection with live SARS-CoV-2 sharply induces KSHV lytic reactivation. Transcriptomic analysis revealed significant changes in global cellular gene expression in KSHV-infected A549-hACE2 cells, both with and without SARS-CoV-2 co-infection. These data provide a molecular basis for understanding whether patients with pre-existing oncogenic herpesvirus infections are at increased risk for more severe COVID-19 or for developing virus-associated cancers even after full recovery from COVID-19.
新型冠状病毒SARS-CoV-2（即COVID-19大流行的病原体）的爆发已导致超过700万人确诊死亡。除了严重的呼吸道和全身症状外，一些合并症还会增加死亡风险。因此，研究COVID-19对患者原有疾病（如癌症和其他传染病）的影响至关重要。最近的临床研究报告称，在重症COVID-19患者或接种疫苗的个体中，包括卡波西肉瘤相关疱疹病毒（KSHV）在内的人类疱疹病毒会重新激活。为了支持这些临床观察结果，我们在A549-hACE2细胞中建立了KSHV/SARS-CoV-2共感染系统。我们的研究结果表明，与活的SARS-CoV-2共同感染会急剧诱导KSHV裂解性再激活。转录组分析显示，在有或没有SARS-CoV-2共感染的情况下，KSHV感染的A549-hACE2细胞中全球细胞基因表达都有显著变化。这些数据为理解原有致癌性疱疹病毒感染的患者是否面临更严重COVID-19的风险增加，或即使从COVID-19完全康复后是否有患病毒相关癌症的风险提供了分子基础。
