SARS-CoV-2 Establishes a Productive Infection in Hepatoma and Glioblastoma Multiforme Cell Lines

Abstract

Severe acute respiratory syndrome associated coronavirus 2 (SARS-CoV-2) emerged at the end of 2019 and rapidly caused a pandemic that led to the death of >6 million people due to hypercoagulation and cytokine storm. In addition, SARS-CoV-2 triggers a wide array of pathologies, including liver dysfunction and neurological disorders. It remains unclear if these events are due to direct infection of the respective tissues or result from systemic inflammation. Here, we explored the possible infection of hepatic and CNS cell lines by SARS-CoV-2. We show that even moderate expression levels of the angiotensin-converting enzyme 2 (ACE2) are sufficient for productive infection. SARS-CoV-2 infects hepatoma Huh7.5 and HepG2 cells but not non-transformed liver progenitor or hepatocyte/cholangiocyte-like HepaRG cells. However, exposure to the virus causes partial dedifferentiation of HepaRG cells. SARS-CoV-2 can also establish efficient replication in some low-passage, high-grade glioblastoma cell lines. In contrast, embryonal primary astrocytes or neuroblastoma cells did not support replication of the virus. Glioblastoma cell permissiveness is associated with defects in interferon production. Overall, these results suggest that liver dysfunction during COVID-19 is not due to infection of these tissues by SARS-CoV-2. Furthermore, tumors may potentially serve as reservoirs for the virus during infection.

Nucleoside Analogs That Inhibit SARS-CoV-2 Replication by Blocking Interaction of Virus Polymerase with RNA

“…Infectious and hemagglutination activities were quantified according to the protocols recommended by the World Health Organization (WHO) [ 40 ]. The multiplicity of infection for SARS-CoV-2 was determined by immunostaining of Vero E cells as described in [ 41 ].…”

Natural Target‐Mimicking Translocation‐Based Fluorescent Sensor for Detection of SARS‐CoV‐2 PLpro Protease Activity and Virus Infection in Living Cells

“…Ratio calculations confirmed a robust high-contrast readout provided by the reporter. Next, we evaluated the performance of the reporter in the context of SARS-CoV-2 infection in human hepatoma Huh7.5 cell line that is permissive to SARS-CoV-2 infection [19]. To increase reproducibility of imaging experiments, we generated a stable line of Huh7.5 cells expressing PLpro-ERNuc by lentiviral transduction.…”

“…Infection with SARS-CoV-2 was performed as described in [19]. Briefly, when the cells on confocal dishes reached 40% density, the virus was added for two hours in DMEM with 2.5% serum at a multiplicity of infection (MOI) 0.1.…”

Unwinding the SARS-CoV-2 Ribosomal Frameshifting Pseudoknot with LNA and G-Clamp-Modified Phosphorothioate Oligonucleotides Inhibits Viral Replication

“…The latter was added to account for the presumed susceptibility of cancer cells to SARS-CoV-2 infection [35]. GBM6138 cells are particularly susceptible to SARS-CoV-2 due to the deficient production of interferon type 1 and overexpression of ACE2 [36]. In the future, additional tests with epithelial and/or respiratory tissue-derived cells may be required for the comprehensive characterization of the AS ONs.…”