SEARCH OF CDNA OF HEPATITIS C VIRUS

THE MOLECULAR BASES OF HEPATITIS C VIRUS (HCV) PERSISTENCE ARE LARGELY UNKNOWN. CURRENT MODELS ASSUME THAT THE VIRUS GENETIC MATERIAL REMAINS AS RNA IN THE INFECTED CELL. OUR HYPOTHESIS IS THAT ENDOGENOUS RETROTRANSCRIPTASES ENCODED BY CELLULAR RETROELEMENTS CAN PRODUCE CDNA COPIES OF HCV RNA. WE HAVE HIGH FITNESS HCV POPULATIONS THAT ORIGINATE ELEVATED INTRACELLULAR LEVELS OF HCV RNA THAT SHOULD FAVOR BINDING OF ENDOGENOUS RETROTRANSCRIPTASES AND SYNTHESIS OF HCV CDNA, WITH OR WITHOUT INTEGRATION INTO CELLULAR DNA. WE HAVE ALSO A LARGE COLLECTION OF OLIGONUCLEOTIDE PRIMERS THAT CAN COPY AND AMPLIFY ANY HCV GENOMIC REGION. WE WILL APPLY WALKING TO IDENTIFY THE CELLULAR NUCLEOTIDE SEQUENCE CONTEXT IN WHICH HCV CDNA IS LOCATED. THE PRESENCE OF HCV CDNA COULD EXPLAIN CELLULAR ALTERATIONS THAT FAVOR VIRAL PERSISTENCE, AS WELL AS CELL SEQUELS THAT ARE OBSERVED IN HEPATIC CELLS ONCE THE VIRUS HAS BEEN ELIMINATED BY ANTIVIRAL TREATMENTS. THE PRESENCE OF CDNA WOULD BE A TURNING POINT IN OUR UNDERSTANDING OF PERSISTENT INFECTIONS OF ANIMAL RNA VIRUSES.