TY - JOUR
T1 - SARS-CoV-2 replicates and displays oncolytic properties in clear cell and papillary renal cell carcinoma
AU - Choong, Oi Kuan
AU - Jakobsson, Rasmus
AU - Bergdahl, Anna Grenabo
AU - Brunet, Sofia
AU - Kärmander, Ambjörn
AU - Waldenström, Jesper
AU - Arvidsson, Yvonne
AU - Altiparmak, Gülay
AU - Nilsson, Jonas A.
AU - Karlsson, Joakim
AU - Nyström, Kristina
AU - Johansson, Martin E.
N1 - Funding Information:
MJ: Grant number 21 1767 Pj 01 H from The Swedish Cancer Society (Cancerfonden) MJ: The National Association against Kidney Diseases. MJ: Grant number 71390 Swedish Government Funding of Clinical Research within the National Health Service (ALF), MJ: The strategic research programme BioCARE, RJ: Grant number 273289 The Research Fund (R&D) at Skaraborg Hospital, Skövde, Sweden and the Healthcare Committee, Region Västra Götaland, Sweden. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Publisher Copyright:
Copyright: © 2023 Choong et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
PY - 2023/1
Y1 - 2023/1
N2 - The SARS-CoV-2 virus is currently causing a global pandemic. Infection may result in a systemic disease called COVID-19, affecting primarily the respiratory tract. Often the gastrointestinal tract and kidneys also become involved. Angiotensin converting enzyme 2 (ACE2) serves as the receptor for SARS-CoV-2. The membrane proteins, Transmembrane serine protease 2 (TMPRSS2) and Neuropilin 1 (NRP1) are accessory proteins facilitating the virus entry. In this study we show that the human proximal kidney tubules, express these factors. We hypothesized that cancers derived from proximal tubules as clear cell (CCRCC) and papillary renal cell carcinoma (PRCC), retain the expression of the SARS-CoV-2 entry factors making these cancers susceptible to SARS-CoV-2 infection. We used bioinformatics, western blotting, and assessment of tissue micro arrays (TMA) including 263 cases of CCRCC, 139 cases of PRCC and 18 cases of chromophobe RCC to demonstrate that the majority of CCRCC and PRCC cases retained the RNA and protein expression of the entry factors for SARS-CoV-2. We furthermore show that SARS-CoV-2 virus propagated robustly in primary cultures of CCRCC and PRCC cells with a visible virus cytopathogenic effect correlating with viral RNA expression levels. We also noted that the delta-variant of SARSCoV-2 causes cancer cells to form syncytia in-vitro. This phenomenon was also identified histologically in CCRCC tissue from a patient that had been hospitalized for COVID-19, twelve months prior to nephrectomy. Our data provide insights into SARS-CoV-2 infectivity in renal cell carcinoma and that the virus causes a distinct cytopathogenic effect.
AB - The SARS-CoV-2 virus is currently causing a global pandemic. Infection may result in a systemic disease called COVID-19, affecting primarily the respiratory tract. Often the gastrointestinal tract and kidneys also become involved. Angiotensin converting enzyme 2 (ACE2) serves as the receptor for SARS-CoV-2. The membrane proteins, Transmembrane serine protease 2 (TMPRSS2) and Neuropilin 1 (NRP1) are accessory proteins facilitating the virus entry. In this study we show that the human proximal kidney tubules, express these factors. We hypothesized that cancers derived from proximal tubules as clear cell (CCRCC) and papillary renal cell carcinoma (PRCC), retain the expression of the SARS-CoV-2 entry factors making these cancers susceptible to SARS-CoV-2 infection. We used bioinformatics, western blotting, and assessment of tissue micro arrays (TMA) including 263 cases of CCRCC, 139 cases of PRCC and 18 cases of chromophobe RCC to demonstrate that the majority of CCRCC and PRCC cases retained the RNA and protein expression of the entry factors for SARS-CoV-2. We furthermore show that SARS-CoV-2 virus propagated robustly in primary cultures of CCRCC and PRCC cells with a visible virus cytopathogenic effect correlating with viral RNA expression levels. We also noted that the delta-variant of SARSCoV-2 causes cancer cells to form syncytia in-vitro. This phenomenon was also identified histologically in CCRCC tissue from a patient that had been hospitalized for COVID-19, twelve months prior to nephrectomy. Our data provide insights into SARS-CoV-2 infectivity in renal cell carcinoma and that the virus causes a distinct cytopathogenic effect.
UR - http://www.scopus.com/inward/record.url?scp=85145430993&partnerID=8YFLogxK
U2 - 10.1371/journal.pone.0279578
DO - 10.1371/journal.pone.0279578
M3 - Article
C2 - 36595529
AN - SCOPUS:85145430993
SN - 1932-6203
VL - 18
JO - PLoS One
JF - PLoS One
IS - 1 January
M1 - e0279578
ER -