Increased hydroxymethylglutaryl coenzyme A reductase activity during respiratory syncytial virus infection mediates actin dependent inter-cellular virus transmission

• Published in: Antiviral research Vol. 100; no. 1; pp. 259 - 268
• Main Authors: Ravi, Laxmi Iyer, Liang, Li, Wong, Pui San, Brown, Gaie, Tan, Boon Huan, Sugrue, Richard J.
• Format: Journal Article
• Language: English
• Published: Kidlington Elsevier B.V 01-10-2013; Elsevier
• Subjects: Actin; Actins - metabolism; Antibiotics. Antiinfectious agents. Antiparasitic agents; Antiviral agents; Antiviral Agents - pharmacology; Biological and medical sciences; Cytochalasin D - pharmacology; Hep G2 Cells; Human viral diseases; Humans; Hydroxymethylglutaryl CoA Reductases - metabolism; Hydroxymethylglutaryl coenzyme A reductase; Infectious diseases; Lovastatin; Medical sciences; Pharmacology. Drug treatments; Respiratory syncytial virus; Respiratory Syncytial Virus Infections - enzymology; Respiratory Syncytial Virus Infections - metabolism; Respiratory Syncytial Virus Infections - virology; Respiratory Syncytial Viruses - drug effects; Respiratory Syncytial Viruses - physiology; Viral diseases; Viral diseases of the respiratory system and ent viral diseases; Virus assembly; Virus transmission; Lovastatin; Hydroxymethylglutaryl coenzyme A reductase; Respiratory syncytial virus; Virus assembly; Virus transmission; Actin; Human respiratory syncytial virus; Transmission; Hypocholesterolemic agent; Paramyxoviridae; Respiratory tract; HMG-CoA reductase inhibitor; Pneumovirus; Pneumovirinae; Enzyme; Enzyme inhibitor; Statin derivative; In vitro; Infection; Virus; Mononegavirales; Viral disease; Hydroxymethylglutaryl-CoA reductase; Oxidoreductases; Antilipemic agent
• ISSN: 0166-3542; 1872-9096
• DOI: 10.1016/j.antiviral.2013.08.012

•RSV particles mature as virus filaments.•Virus transmission occurs by virus filaments.•RSV filament formation is inhibited by lovastatin.•Lovastatin inhibits RSV transmission.•Hydroxymetylglutaryl coenzyme A reductase mediates virus transmission.
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.