title: The Rift Valley fever accessory proteins NSm and P78/NSm-GN are distinct determinants of virus propagation in vertebrate and invertebrate hosts.
abstract: Rift Valley fever virus (RVFV) is an enzootic virus circulating in Africa that is transmitted to its vertebrate host by a mosquito vector and causes severe clinical manifestations in humans and ruminants. RVFV has a tripartite genome of negative or ambisense polarity. The M segment contains five in-frame AUG codons that are alternatively used for the synthesis of two major structural glycoproteins, GN and GC, and at least two accessory proteins, NSm, a 14-kDa cytosolic protein, and P78/NSm-GN, a 78-kDa glycoprotein. To determine the relative contribution of P78 and NSm to RVFV infectivity, AUG codons were knocked out to generate mutant viruses expressing various sets of the M-encoded proteins. We found that, in the absence of the second AUG codon used to express NSm, a 13-kDa protein corresponding to an N-terminally truncated form of NSm, named NSm', was synthesized from AUG 3. None of the individual accessory proteins had any significant impact on RVFV virulence in mice. However, a mutant virus lacking both NSm and NSm' was strongly attenuated in mice and grew to reduced titers in murine macrophages, a major target cell type of RVFV. In contrast, P78 was not associated with reduced viral virulence in mice, yet it appeared as a major determinant of virus dissemination in mosquitoes. This study demonstrates how related accessory proteins differentially contribute to RVFV propagation in mammalian and arthropod hosts.
authors.affiliation: Molecular Genetics of Bunyaviruses, Institut Pasteur , F-75015 Paris, France ; Structural Virology, Institut Pasteur , F-75015 Paris, France ; Univ Paris Diderot, Sorbonne Paris Cité , F-75205 Paris, France.
authors.forename: Felix
authors.initials: F
authors.lastname: Kreher
authors.affiliation: Molecular Genetics of Bunyaviruses, Institut Pasteur , F-75015 Paris, France ; Structural Virology, Institut Pasteur , F-75015 Paris, France.
authors.forename: Carole
authors.initials: C
authors.lastname: Tamietti
authors.affiliation: Mouse Functional Genetics, Institut Pasteur , F-75015 Paris, France ; CNRS URA 2578, Institut Pasteur , F-75015 Paris, France ; Central Animal Facilities, Institut Pasteur , F-75015 Paris, France.
authors.forename: Céline
authors.initials: C
authors.lastname: Gommet
authors.affiliation: Mouse Functional Genetics, Institut Pasteur , F-75015 Paris, France ; CNRS URA 2578, Institut Pasteur , F-75015 Paris, France.
authors.forename: Laurent
authors.initials: L
authors.lastname: Guillemot
authors.affiliation: Molecular Genetics of Bunyaviruses, Institut Pasteur , F-75015 Paris, France.
authors.forename: Myriam
authors.initials: M
authors.lastname: Ermonval
authors.affiliation: Arboviruses and Insect Vectors, Institut Pasteur , F-75015 Paris, France.
authors.forename: Anna-Bella
authors.initials: AB
authors.lastname: Failloux
authors.affiliation: Mouse Functional Genetics, Institut Pasteur , F-75015 Paris, France ; CNRS URA 2578, Institut Pasteur , F-75015 Paris, France.
authors.forename: Jean-Jacques
authors.initials: JJ
authors.lastname: Panthier
authors.affiliation: Molecular Genetics of Bunyaviruses, Institut Pasteur , F-75015 Paris, France.
authors.forename: Michèle
authors.initials: M
authors.lastname: Bouloy
authors.affiliation: Molecular Genetics of Bunyaviruses, Institut Pasteur , F-75015 Paris, France ; Structural Virology, Institut Pasteur , F-75015 Paris, France.
authors.forename: Marie
authors.initials: M
authors.lastname: Flamand
keywords: arbovirus; attenuation; bunyavirus; minor structural protein; non-structural protein; transmission; vector; virulence factor