title: Ribavirin inhibits human parainfluenza virus type 2 replication in vitro.
abstract: The antiviral activities of eight nucleoside analog antiviral drugs (ribavirin, acyclovir, lamivudine, 3'-azido-3'-deoxythymidine, emtricitabine, tenofovir, penciclovir and ganciclovir) against human parainfluenza virus type 2 (hPIV-2) were investigated. Only ribavirin (RBV) inhibited both cell fusion and hemadsorption induced by hPIV-2. RBV considerably reduced the number of viruses released from the cells. Virus genome synthesis was inhibited by RBV, as determined by real time PCR. An indirect immunofluorescence study showed that RBV largely inhibited viral protein synthesis. mRNAs of the proteins were not detected, indicating that inhibition of protein synthesis was caused by transcription inhibition by RBV. Using a recombinant green fluorescence protein-expressing hPIV-2 without matrix protein, it was found that RBV did not completely inhibit virus entry into the cells; however, it almost completely blocked multinucleated giant cell formation. RBV did not disrupt actin microfilaments and microtubules. These results indicate that the inhibitory effect of RBV is caused by inhibition of both virus genome and mRNA synthesis, resulting in inhibition of virus protein synthesis, viral replication and multinucleated giant cell formation (extensive cell-to-cell spreading of the virus).
authors.affiliation: Department of Clinical Nutrition, Faculty of Health Science, Suzuka University of Medical Science.
authors.forename: Sahoko
authors.initials: S
authors.lastname: Kihira
authors.forename: Jun
authors.initials: J
authors.lastname: Uematsu
authors.forename: Mitsuo
authors.initials: M
authors.lastname: Kawano
authors.forename: Ai
authors.initials: A
authors.lastname: Itoh
authors.forename: Ayumi
authors.initials: A
authors.lastname: Ookohchi
authors.forename: Saemi
authors.initials: S
authors.lastname: Satoh
authors.forename: Yurie
authors.initials: Y
authors.lastname: Maeda
authors.forename: Kae
authors.initials: K
authors.lastname: Sakai
authors.forename: Hidetaka
authors.initials: H
authors.lastname: Yamamoto
authors.forename: Masato
authors.initials: M
authors.lastname: Tsurudome
authors.forename: Myles
authors.initials: M
authors.lastname: O'Brien
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Komada
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology*; D002460:Cell Line; D019084:Fluorescent Antibody Technique, Indirect; D008253:Macaca mulatta; D010223:Parainfluenza Virus 2, Human / Q000187:drug effects* / Q000502:physiology*; D012367:RNA, Viral / Q000096:biosynthesis; D060888:Real-Time Polymerase Chain Reaction; D012254:Ribavirin / Q000494:pharmacology*; D014158:Transcription, Genetic / Q000187:drug effects; D014764:Viral Proteins / Q000096:biosynthesis; D014779:Virus Replication / Q000187:drug effects*
chemical_list: D000998:Antiviral Agents; D012367:RNA, Viral; D014764:Viral Proteins; D012254:Ribavirin
keywords: antiviral drugs; human parainfluenza virus type 2; recombinant green fluorescence protein expressing hPIV-2 without matrix protein