Exosomes from Hepatitis C Infected Patients Transmit HCV Infection and Contain Replication Competent Viral RNA in Complex with Ago2-miR122-HSP90

Antibodies targeting receptor-mediated entry of hcv into hepatocytes confer limited therapeutic benefits. evidence suggests that exosomes can transfer genetic materials between cells; however,their role in hcv infection remains obscure. here,we show that exosomes isolated from sera of chronic hcv infected patients or supernatants of j6/jfh1-hcv-infected huh7.5 cells contained hcv rna. these exosomes could mediate viral receptor-independent transmission of hcv to hepatocytes. negative sense hcv rna,indicative of replication competent viral rna,was present in exosomes of all hcv infected treatment non-responders and some treatment-naïve individuals. remarkably,hcv rna was associated with ago2,hsp90 and mir-122 in exosomes isolated from hcv-infected individuals or hcv-infected huh7.5 cell supernatants. exosome-loading with a mir-122 inhibitor,or inhibition of hsp90,vacuolar h+-atpases,and proton pumps,significantly suppressed exosome-mediated hcv transmission to naïve cells. our findings provide mechanistic evidence for hcv transmission by blood-derived exosomes and highlight potential therapeutic strategies. © 2014 bukong et al.