title: Nuclear relocalization of polyadenylate binding protein during rift valley fever virus infection involves expression of the NSs gene.
abstract: Rift Valley fever virus (RVFV), an ambisense member of the family Bunyaviridae, genus Phlebovirus, is the causative agent of Rift Valley fever, an important zoonotic infection in Africa and the Middle East. Phlebovirus proteins are translated from virally transcribed mRNAs that, like host mRNA, are capped but, unlike host mRNAs, are not polyadenylated. Here, we investigated the role of PABP1 during RVFV infection of HeLa cells. Immunofluorescence studies of infected cells demonstrated a gross relocalization of PABP1 to the nucleus late in infection. Immunofluorescence microscopy studies of nuclear proteins revealed costaining between PABP1 and markers of nuclear speckles. PABP1 relocalization was sharply decreased in cells infected with a strain of RVFV lacking the gene encoding the RVFV nonstructural protein S (NSs). To determine whether PABP1 was required for RVFV infection, we measured the production of nucleocapsid protein (N) in cells transfected with small interfering RNAs (siRNAs) targeting PABP1. We found that the overall percentage of RVFV N-positive cells was not changed by siRNA treatment, indicating that PABP1 was not required for RVFV infection. However, when we analyzed populations of cells producing high versus low levels of PABP1, we found that the percentage of RVFV N-positive cells was decreased in cell populations producing physiologic levels of PABP1 and increased in cells with reduced levels of PABP1. Together, these results suggest that production of the NSs protein during RVFV infection leads to sequestration of PABP1 in the nuclear speckles, creating a state within the cell that favors viral protein production.
authors: United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, Frederick, Maryland, USA.
authors: Anna Maria
authors: AM
authors: Copeland
authors: Louis A
authors: LA
authors: Altamura
authors: Nicole M
authors: NM
authors: Van Deusen
authors: Connie S
authors: CS
authors: Schmaljohn
mesh_terms: D002467:Cell Nucleus / Q000378:metabolism*; D017353:Gene Deletion; D006367:HeLa Cells; D054884:Host-Pathogen Interactions; D006801:Humans; D018613:Microscopy, Confocal; D008856:Microscopy, Fluorescence; D039122:Poly(A)-Binding Protein I / Q000378:metabolism*; D012296:Rift Valley fever virus / Q000235:genetics / Q000502:physiology*; D017361:Viral Nonstructural Proteins / Q000235:genetics / Q000378:metabolism*; D014779:Virus Replication
chemical_list: D039122:Poly(A)-Binding Protein I; D017361:Viral Nonstructural Proteins
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