ArticlePLoS neglected tropical diseases2021
Rift Valley fever virus 78kDa envelope protein attenuates virus replication in macrophage-derived cell lines and viral virulence in mice.
Article in PLoS neglected tropical diseases, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 17 citations in OpenAlex.
- Pathogenicity of Rift Valley fever virus: Organ-specific clinical outcomes and hidden drivers of virulence - a narrative review.Virulence · 2026Review
- Opportunities and challenges for countermeasures against Rift Valley fever virus: A quintessential One Health pathogen.PLoS neglected tropical diseases · 2026Review
- Genetic diversity of Toscana virus glycoproteins affects the kinetics of virus entry and the infectivity of newly produced virions.Npj viruses · 2025Article
- Novel replication-competent reporter-expressing Rift Valley fever viruses for molecular studies.Journal of virology · 2025Article
- Use of Rift Valley Fever Virus Expressing NanoLuc Luciferase for the Assessment of Neutralizing Antibodies and Antivirals.Methods in molecular biology (Clifton, N.J.) · 2025Article
- Comparative study of two Rift Valley fever virus field strains originating from Mauritania.PLoS neglected tropical diseases · 2024Article
- Rift Valley fever virus is able to cross the human blood-brain barrierJournal of virology · 2024Article
- Cloning and phylogenetic analysis of N protein gene from Rift Valley Fever Virus (RVFV).Bioinformation · 2024Article
- Article
- Advancements in Rift Valley fever vaccines: a historical overview and prospects for next generation candidates.NPJ vaccines · 2023Review
- Perspectives of Next-Generation Live-Attenuated Rift Valley Fever Vaccines for Animal and Human Use.Vaccines · 2023Review
- Mechanistic insight into the efficient packaging of antigenomic S RNA into Rift Valley fever virus particles.Frontiers in cellular and infection microbiology · 2023Article
- Identification of Single Amino Acid Changes in the Rift Valley Fever Virus Polymerase Core Domain Contributing to Virus AttenuationFrontiers in cellular and infection microbiology · 2022Article
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
Rift Valley fever virus (RVFV) is a mosquito-borne bunyavirus with a wide host range including ruminants and humans. RVFV outbreaks have had devastating effects on public health and the livestock industry in African countries. However, there is no approved RVFV vaccine for human use in non-endemic countries and no FDA-approved antiviral drug for RVFV treatment. The RVFV 78kDa protein (P78), which is a membrane glycoprotein, plays a role in virus dissemination in the mosquito host, but its biological role in mammalian hosts remains unknown. We generated an attenuated RVFV MP-12 strain-derived P78-High virus and a virulent ZH501 strain-derived ZH501-P78-High virus, both of which expressed a higher level of P78 and carried higher levels of P78 in the virion compared to their parental viruses. We also generated another MP-12-derived mutant virus (P78-KO virus) that does not express P78. MP-12 and P78-KO virus replicated to similar levels in fibroblast cell lines and Huh7 cells, while P78-High virus replicated better than MP-12 in Vero E6 cells, fibroblast cell lines, and Huh7 cells. Notably, P78-High virus and P78-KO virus replicated less efficiently and more efficiently, respectively, than MP-12 in macrophage cell lines. ZH501-P78-High virus also replicated poorly in macrophage cell lines. Our data further suggest that inefficient binding of P78-High virus to the cells led to inefficient virus internalization, low virus infectivity and reduced virus replication in a macrophage cell line. P78-High virus and P78-KO virus showed lower and higher virulence than MP-12, respectively, in young mice. ZH501-P78-High virus also exhibited lower virulence than ZH501 in mice. These data suggest that high levels of P78 expression attenuate RVFV virulence by preventing efficient virus replication in macrophages. Genetic alteration leading to increased P78 expression may serve as a novel strategy for the attenuation of RVFV virulence and generation of safe RVFV vaccines.
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