Hypoxic marker CA IX and adhesion mediator β-catenin are downregulated by lymphocytic choriomeningitis virus persistent infection

// Andrea Fabianova 1 , Monika Barathova 1 , Lucia Csaderova 1 , Veronika Simko 1 , Miriam Zatovicova 1 , Martina Labudova 1 and Jaromir Pastorek 1, 2 1 Institute of Virology, Biomedical Research Center, Slovak Academy of Sciences, Bratislava 845 05, Slovak Republic 2 Department of Chemistry, Faculty of Natural Sciences, University of SS. Cyril and Methodius, Trnava 917 01, Slovak Republic Correspondence to: Martina Labudova, email: virulama@savba.sk Keywords: carbonic anhydrase IX; lymphocytic choriomeningitis virus; renal cell carcinoma; internalization; immunotherapy Received: September 06, 2017      Accepted: January 25, 2018      Published: February 02, 2018 ABSTRACT Renal cell carcinoma is one of the most frequent cancer diseases with high resistance to radio- and chemotherapy. Mutation of VHL gene is frequent in these tumors leading to simulation of hypoxic conditions. Lymphocytic choriomeningitis virus, belonging to RNA viruses, is a neglected human pathogen and teratogen. We have found that infection of renal cell carcinoma cells by lymphocytic choriomeningitis virus strain MX causes a decrease of carbonic anhydrase IX protein and RNA level. Lower expression of carbonic anhydrase IX on the cell surface provides less target for carbonic anhydrase IX-targeted immunotherapy. What more, reduced levels of adhesion mediating protein β-catenin as well as E-cadherin, as a consequence of infection, suggest a possible increase in metastatic potential of cells infected by lymphocytic choriomeningitis virus strain MX. These results might help elucidate differences in patients susceptibility to immunotherapy directed against carbonic anhydrase IX or in developing new therapeutical strategies. Our data indicate that presence of infection can significantly affect patient response to cancer therapy.