title: The MVMp P4 promoter is a host cell-type range determinant in vivo.
abstract: The protoparvovirus early promoters, e.g. P4 of Minute Virus of Mice (MVM), play a critical role during infection. Initial P4 activity depends on the host transcription machinery only. Since this is cell-type dependent, it is hypothesized that P4 is a host cell-type range determinant. Yet host range determinants have mapped mostly to capsid, never P4. Here we test the hypothesis using the mouse embryo as a model system. Disruption of the CRE element of P4 drastically decreased infection levels without altering range. However, when we swapped promoter elements of MVM P4 with those from equivalent regions of the closely related H1 virus, we observed elimination of infection in fibroblasts and chondrocytes and the acquisition of infection in skeletal muscle. We conclude that P4 is a host range determinant and a target for modifying the productive infection potential of the virus - an important consideration in adapting these viruses for oncotherapy.
authors.affiliation: Department of Microbiology, Immunology and Genetics, Faculty of Health Sciences, Ben Gurion University of the Negev, Beer Sheva, Israel.
authors.forename: Chen
authors.initials: C
authors.lastname: Meir
authors.affiliation: Department of Microbiology, Immunology and Genetics, Faculty of Health Sciences, Ben Gurion University of the Negev, Beer Sheva, Israel.
authors.forename: Michal
authors.initials: M
authors.lastname: Mincberg
authors.affiliation: Department of Microbiology, Immunology and Genetics, Faculty of Health Sciences, Ben Gurion University of the Negev, Beer Sheva, Israel.
authors.forename: Irina
authors.initials: I
authors.lastname: Rostovsky
authors.affiliation: Department of Microbiology, Immunology and Genetics, Faculty of Health Sciences, Ben Gurion University of the Negev, Beer Sheva, Israel.
authors.forename: Saar
authors.initials: S
authors.lastname: Tal
authors.affiliation: Departments of Laboratory Medicine and Genetics, Yale University School of Medicine, New Haven, CT, USA.
authors.forename: Ellen M
authors.initials: EM
authors.lastname: Vollmers
authors.affiliation: Department of Microbiology, Immunology and Genetics, Faculty of Health Sciences, Ben Gurion University of the Negev, Beer Sheva, Israel.
authors.forename: Adi
authors.initials: A
authors.lastname: Levi
authors.affiliation: Departments of Laboratory Medicine and Genetics, Yale University School of Medicine, New Haven, CT, USA.
authors.forename: Peter
authors.initials: P
authors.lastname: Tattersall
authors.affiliation: Department of Microbiology, Immunology and Genetics, Faculty of Health Sciences, Ben Gurion University of the Negev, Beer Sheva, Israel. Electronic address: clay@bgu.ac.il.
authors.forename: Claytus
authors.initials: C
authors.lastname: Davis
mesh_terms: D000818:Animals; D015967:Gene Expression Regulation, Viral; D058507:Host Specificity; D051379:Mice; D008915:Minute Virus of Mice / Q000235:genetics / Q000502:physiology*; D010322:Parvoviridae Infections / Q000821:virology*; D011401:Promoter Regions, Genetic; D012376:Rodent Diseases / Q000821:virology*; D017361:Viral Nonstructural Proteins / Q000235:genetics* / Q000378:metabolism; D014779:Virus Replication
chemical_list: D017361:Viral Nonstructural Proteins
keywords: Autonomous parvovirus; Host-range determinant; MVM; P4 promoter; Protoparvovirus; Viral transcription