Fat(al) attraction Picornaviruses Usurp Lipid Transfer at Membrane Contact Sites to Create Replication Organelles.pdfVIP

Review Fat(al) attraction: Picornaviruses Usurp Lipid Transfer at Membrane Contact Sites to Create Replication Organelles Hilde M. van der Schaar,1 Cristina M. Dorobantu,1 Lucian Albulescu,1 Jeroen R.P.M. Strating,1 and Frank J.M. van Kuppeveld1,* All viruses that carry a positive-sense RNA genome (+RNA), such as picornaviruses, hepatitis C virus, dengue virus, and SARS- and MERS-coronavirus, con?scate intracellular membranes of the host cell to generate new compartments (i.e., replication organelles) for ampli?cation of their genome. Replication organelles (ROs) are membranous structures that not only harbor viral proteins but also contain a speci?c array of hijacked host factors that create a unique lipid microenvironment optimal for genome replication. While some lipids may be locally synthesized de novo, other lipids are shuttled towards ROs. In picornavirusinfected cells, lipids are exchanged at membrane contact sites between ROs and other organelles. In this paper, we review recent advances in our understanding of how picornaviruses exploit host membrane contact site machinery to generate ROs, a mechanism that is used by some other +RNA viruses as well. Trends Picornaviruses create replication organelles with a unique protein and lipid composition to amplify their genome. Picornaviruses hijack membrane contact site machinery to shuttle lipids to their replication organelles. Picornaviruses from different genera employ a cholesterol/PI4P counter?ux mechanism to accumulate cholesterol at replication organelles. Picornaviruses and Their Life Cycle The Picornaviridae constitute a large family of positive-sense, single-stranded RNA (+RNA) viruses comprising many human and animal pathogens associated with a wide spectrum of diseases (Box 1) (reviewed in [1]). The family currently consists of 29 genera (). Most studies have focused on the Enterovirus genus, which includes poliovirus, coxsackie A and B viruses, and human rhinoviruses; these viruses have a great clinic