title: Increased hydroxymethylglutaryl coenzyme A reductase activity during respiratory syncytial virus infection mediates actin dependent inter-cellular virus transmission.
abstract: We have examined the role that hydroxymethylglutaryl coenzyme A reductase (HMGCR) plays during respiratory syncytial virus (RSV) maturation. Imaging analysis indicated that virus-induced changes in F-actin structure correlated with the formation of virus filaments, and that these virus filaments played a direct role in virus cell-to-cell transmission. Treatment with cytochalasin D (CYD) prevented virus filament formation and virus transmission, but this could be reversed by removal of CYD. This observation, together with the presence of F-actin within the virus filaments suggested that newly polymerised F-actin was required for virus transmission. The virus-induced change in F-actin was inhibited by the HMGCR inhibitor lovastatin, and this correlated with the inhibition of both virus filament formation and the incorporation of F-actin in these virus structures. Furthermore, this inhibitory effect on virus filament formation correlated with a significant reduction in RSV transmission. Collectively these data suggested that HMGCR-mediated changes in F-actin structure play an important role in the inter-cellular transmission of mature RSV particles. These data also highlighted the interplay between cellular metabolism and RSV transmission, and demonstrate that this interaction can be targeted using anti-virus strategies.
authors.affiliation: Division of Molecular and Cell Biology, School of Biological Sciences, Nanyang Technological University, 60 Nanyang Drive, Singapore 637551, Singapore.
authors.forename: Laxmi Iyer
authors.initials: LI
authors.lastname: Ravi
authors.forename: Li
authors.initials: L
authors.lastname: Liang
authors.forename: Pui San
authors.initials: PS
authors.lastname: Wong
authors.forename: Gaie
authors.initials: G
authors.lastname: Brown
authors.forename: Boon Huan
authors.initials: BH
authors.lastname: Tan
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Sugrue
mesh_terms: D000199:Actins / Q000378:metabolism*; D000998:Antiviral Agents / Q000494:pharmacology; D015638:Cytochalasin D / Q000494:pharmacology; D056945:Hep G2 Cells; D006801:Humans; D006903:Hydroxymethylglutaryl CoA Reductases / Q000378:metabolism*; D018357:Respiratory Syncytial Virus Infections / Q000201:enzymology* / Q000378:metabolism / Q000821:virology*; D012136:Respiratory Syncytial Viruses / Q000187:drug effects / Q000502:physiology*
chemical_list: D000199:Actins; D000998:Antiviral Agents; D015638:Cytochalasin D; D006903:Hydroxymethylglutaryl CoA Reductases
keywords: Actin; Hydroxymethylglutaryl coenzyme A reductase; Lovastatin; Respiratory syncytial virus; Virus assembly; Virus transmission