title: Positive-strand RNA viruses stimulate host phosphatidylcholine synthesis at viral replication sites.
abstract: All positive-strand RNA viruses reorganize host intracellular membranes to assemble their viral replication complexes (VRCs); however, how these viruses modulate host lipid metabolism to accommodate such membrane proliferation and rearrangements is not well defined. We show that a significantly increased phosphatidylcholine (PC) content is associated with brome mosaic virus (BMV) replication in both natural host barley and alternate host yeast based on a lipidomic analysis. Enhanced PC levels are primarily associated with the perinuclear ER membrane, where BMV replication takes place. More specifically, BMV replication protein 1a interacts with and recruits Cho2p (choline requiring 2), a host enzyme involved in PC synthesis, to the site of viral replication. These results suggest that PC synthesized at the site of VRC assembly, not the transport of existing PC, is responsible for the enhanced accumulation. Blocking PC synthesis by deleting the CHO2 gene resulted in VRCs with wider diameters than those in wild-type cells; however, BMV replication was significantly inhibited, highlighting the critical role of PC in VRC formation and viral replication. We further show that enhanced PC levels also accumulate at the replication sites of hepatitis C virus and poliovirus, revealing a conserved feature among a group of positive-strand RNA viruses. Our work also highlights a potential broad-spectrum antiviral strategy that would disrupt PC synthesis at the sites of viral replication but would not alter cellular processes.
authors: Department of Plant Pathology, Physiology, and Weed Science, Virginia Tech, Blacksburg, VA 24061;
authors: Jiantao
authors: J
authors: Zhang
authors: Department of Plant Pathology, Physiology, and Weed Science, Virginia Tech, Blacksburg, VA 24061; Department of Plant Protection, Fujian Agriculture and Forestry University, Fuzhou 350002, People's Republic of China;
authors: Zhenlu
authors: Z
authors: Zhang
authors: Department of Microbiology, The University of Chicago, Chicago, IL 60637;
authors: Vineela
authors: V
authors: Chukkapalli
authors: Virginia-Maryland Regional College of Veterinary Medicine, University of Maryland, College Park, MD 20742.
authors: Jules A
authors: JA
authors: Nchoutmboube
authors: Department of Plant Pathology, Physiology, and Weed Science, Virginia Tech, Blacksburg, VA 24061;
authors: Jianhui
authors: J
authors: Li
authors: Department of Microbiology, The University of Chicago, Chicago, IL 60637;
authors: Glenn
authors: G
authors: Randall
authors: Virginia-Maryland Regional College of Veterinary Medicine, University of Maryland, College Park, MD 20742.
authors: George A
authors: GA
authors: Belov
authors: Department of Plant Pathology, Physiology, and Weed Science, Virginia Tech, Blacksburg, VA 24061; reachxw@vt.edu.
authors: Xiaofeng
authors: X
authors: Wang
mesh_terms: D017795:Bromovirus / Q000502:physiology*; D004721:Endoplasmic Reticulum / Q000235:genetics / Q000378:metabolism / Q000821:virology; D001467:Hordeum / Q000235:genetics / Q000378:metabolism* / Q000821:virology; D007425:Intracellular Membranes / Q000378:metabolism / Q000821:virology; D010713:Phosphatidylcholines / Q000096:biosynthesis* / Q000235:genetics; D010935:Plant Diseases / Q000821:virology*; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism; D014779:Virus Replication / Q000502:physiology*
chemical_list: D010713:Phosphatidylcholines
keywords: phospholipids; positive-strand RNA viruses; viral replication complexes; virus control; virus–host interactions