Abstract LB072: SARS-CoV-2 proteins and anti-COVID-19 drugs induce lytic reactivation of an oncogenic virus

Abstract

Abstract An outbreak of the novel coronavirus SARS-CoV-2, the causative agent of Coronavirus Disease-2019 (COVID-19), a respiratory disease, has infected over 75,000,000 people since the end of 2019, killed over 1,600,000, and caused worldwide social and economic disruption. Because the mechanisms of SARS-CoV-2 infection of host cells and its pathogenesis remain largely unclear, there are currently no antiviral drugs with proven efficacy. Besides severe respiratory and systematic symptoms, several comorbidities increase risk of fatal disease outcome. Therefore, it is required to investigate the impacts of COVID-19 on pre-existing diseases of patients, such as cancer and other infectious diseases. Kaposi's sarcoma-associated herpesvirus (KSHV) is the etiologic agent of several human cancers, such as Kaposi's sarcoma (KS) and Primary effusion lymphoma (PEL), mostly seen in immunosuppressed patients especially people with HIV infection. In the current study, we for the first time report that SARS-CoV-2 encoded spike (S) and nucleocapsid (N) proteins and some currently used anti-COVID-19 drugs (especially Azithromycin and Nafamostat mesylate) are able to induce lytic reactivation of KSHV from virus infected normal and tumor cells, through manipulation of intracellular signaling pathways. In addition, we found the obvious upregulation of ACE2 expression, the major receptor of SARS-CoV-2, in AIDS-KS tissues, indicating that KSHV may potentially increase SARS-CoV-2 co-infection. Together, our data indicate that those KSHV+ patients especially in endemic areas exposure to COVID-19 or undergoing the treatment may have increased risks to develop these virus-associated cancers, even after they have fully recovered from COVID-19. Citation Format: Zhiqiang Qin, Jungang Chen, Lu Dai, Lindsey Barrett, Steven Post. SARS-CoV-2 proteins and anti-COVID-19 drugs induce lytic reactivation of an oncogenic virus [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr LB072.