Involvement of actin microfilaments in the transcription/replication of human parainfluenza virus type 3: possible role of actin in other viruses.
Multifunctional involvement of actin microfilaments during viral infection has been documented in many studies. The molecular mechanism underlying this important host-virus interaction, however, remains poorly understood. We have investigated the role of actin microfilaments in the life cycle of human parainfluenza virus type 3 (HPIV3), a paramyxovirus that causes severe respiratory illness in children. In vitro transcription with purified viral ribonucleoprotein (RNP) complex showed a requirement of cellular actin, in the polymeric form, for mRNA synthesis in vitro. This was further confirmed by using recombinant actin, which interacted with the viral RNP and also activated mRNA synthesis in vitro. Consistent with the role of the polymeric form of actin, the actin microfilaments of the cytoskeletal framework participate in the virus replication in vivo. Biochemical and immunological analyses revealed the association of viral RNPs with cytoskeletal framework during early stages of infection, and involvement of these RNPs in the synthesis of mRNAs and genome-length RNA. Immunofluorescent labeling and confocal microscopy showed that the viral nucleocapsids colocalize with the actin microfilaments. Treatment of cells with cytochalasin D, which depolymerizes actin microfilaments, inhibited viral RNA synthesis and RNP accumulation. These data indicate that actin microfilaments play a critical role in HPIV3 life cycle, specifically at the level of viral transcription and replication. Involvement of the cytoskeletal framework in the life cycle of several viruses containing RNA and DNA genomes is reviewed.
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Department of Virology, The Lerner Research Institute, The Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA. banerja@ccf.org
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D008841:Actin Cytoskeleton / Q000737:chemistry* / Q000502:physiology; D000199:Actins / Q000494:pharmacology / Q000502:physiology*; D002478:Cells, Cultured; D015638:Cytochalasin D / Q000494:pharmacology; D006801:Humans; D015151:Immunoblotting; D010224:Parainfluenza Virus 3, Human / Q000235:genetics / Q000254:growth & development / Q000502:physiology*; D012333:RNA, Messenger / Q000096:biosynthesis; D011994:Recombinant Proteins / Q000096:biosynthesis; D012261:Ribonucleoproteins / Q000187:drug effects / Q000502:physiology; D014158:Transcription, Genetic / Q000187:drug effects; D014764:Viral Proteins / Q000187:drug effects / Q000502:physiology; D014779:Virus Replication / Q000187:drug effects
D000199:Actins; D012333:RNA, Messenger; D011994:Recombinant Proteins; D012261:Ribonucleoproteins; D014764:Viral Proteins; D015638:Cytochalasin D