Ribavirin Causes Error Catastrophe during Hantaan Virus Replication

摘要: Except for ribavirin, no other antiviral drugs treating hantaviral diseases have been identified. It is well established that ribavirin will inhibit the production of infectious Hantaan virus (HTNV); however, its mechanism action unknown. To characterize inhibitory effect on HTNV, levels viral RNAs, proteins, and particles were measured 3 days posttreatment HTNV-infected Vero E6 cells. cells treated with showed a slight reduction in cRNA, RNA, mRNA populations first day postinfection. The amount cRNA RNA increased to observed untreated 2, whereas more greatly reduced 2 3. Despite finding S-segment mRNA, albeit low, three proteins—nucleocapsid (N) protein glycoproteins G1 G2—could not be detected by immunohistochemistry ribavirin-treated test hypothesis these effects caused incorporation into nascent resultant “error catastrophe” was occurring, we cloned sequenced cRNA/mRNA from or We found high mutation frequency (9.5/1,000 nucleotides) synthesized presence ribavirin. Hence, transcripts produced drug functional. These results suggest ribavirin's lies challenging fidelity hantavirus polymerase, which causes error catastrophe.