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Viruses
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Emerging Highlights in the Study of Rift Valley Fever Virus
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Emerging Highlights in the Study of Rift Valley Fever Virus

A special issue of Viruses (ISSN 1999-4915). This special issue belongs to the section "Animal Viruses".

Deadline for manuscript submissions: closed (30 November 2024) | Viewed by 14831

Special Issue Editors

Dr. Corey L. Campbell

E-Mail Website
Guest Editor
Department of Microbiology, Immunology and Pathology, Colorado State University, Campus Delivery 1690, Fort Collins, CO 80523, USA
Interests: vector biology; arboviruses; mosquito anti-viral responses; molecular biology; mosquito immunity; genomic regulatory regions
Special Issues, Collections and Topics in MDPI journals
Dr. Emma K. Harris

E-Mail Website
Guest Editor
Department of Microbiology, Immunology and Pathology, Colorado State University, Campus Delivery 1690, Fort Collins, CO 80523, USA
Interests: vector competence; arboviruses; tick-borne disease; mosquito biology

Special Issue Information

Dear Colleagues,

The Rift Valley Fever virus periodically emerges in explosive epizootics in Eastern Africa and parts of the Arabian Peninsula. Viral transmission from competent mosquitoes, e.g., Aedes and Culex spp., to vertebrate hosts, can cause severe illness in humans and abortion storms in ungulates. Threats posed by current and shifting dynamics in RVFV transmission necessitate many lines of research, including, but not limited to: 1) knowledge of vector–virus interactions, 2) development of efficient vaccines for vertebrates, 3) viral strain replication kinetics, and 4) pathogenesis models. This Special Issue seeks to cover the gamut of RVFV research areas and will reveal knowledge gaps that need to be further addressed.

Dr. Corey L. Campbell
Dr. Emma K. Harris
Guest Editors

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Keywords

  • Rift Valley fever virus
  • emerging diseases
  • viral reassortment
  • neglected tropical diseases
  • vaccine development
  • vector–virus interactions

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Published Papers (7 papers)

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Research

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16 pages, 1914 KiB  
Article
Co-Infection of Culex tarsalis Mosquitoes with Rift Valley Fever Phlebovirus Strains Results in Efficient Viral Reassortment
by Emma K. Harris, Velmurugan Balaraman, Cassidy C. Keating, Chester McDowell, J. Brian Kimble, Alina De La Mota-Peynado, Erin M. Borland, Barbara Graham, William C. Wilson, Juergen A. Richt, Rebekah C. Kading and Natasha N. Gaudreault
Viruses 2025, 17(1), 88; https://doi.org/10.3390/v17010088 - 11 Jan 2025
Viewed by 1203
Abstract
Rift Valley fever phlebovirus (RVFV) is a zoonotic mosquito-borne pathogen endemic to sub-Saharan Africa and the Arabian Peninsula which causes Rift Valley fever in ruminant livestock and humans. Co-infection with divergent viral strains can produce reassortment among the L, S, and M segments [...] Read more.
Rift Valley fever phlebovirus (RVFV) is a zoonotic mosquito-borne pathogen endemic to sub-Saharan Africa and the Arabian Peninsula which causes Rift Valley fever in ruminant livestock and humans. Co-infection with divergent viral strains can produce reassortment among the L, S, and M segments of the RVFV genome. Reassortment events can produce novel genotypes with altered virulence, transmission dynamics, and/or mosquito host range. This can have severe implications in areas where RVFV is endemic and convolutes our ability to anticipate transmission and circulation in novel geographic regions. Previously, we evaluated the frequency of RVFV reassortment in a susceptible ruminant host and observed low rates of reassortment (0–1.7%). Here, we tested the hypothesis that reassortment occurs predominantly in the mosquito using a highly permissive vector, Culex tarsalis. Cells derived from Cx. tarsalis or adult mosquitoes were co-infected with either two virulent (Kenya-128B-15 and SA01-1322) or a virulent and attenuated (Kenya-128B-15 and MP-12) strain of RVFV. Our results showed approximately 2% of virus genotypes isolated from co-infected Cx. tarsalis-derived cells were reassortant. Co-infected mosquitoes infected via infectious bloodmeal resulted in a higher percentage of reassortant virus (2–60%) isolated from midgut and salivary tissues at 14 days post-infection. The percentage of reassortant genotypes isolated from the midguts of mosquitoes co-infected with Kenya-128B-15 and SA01-1322 was similar to that of mosquitoes co-infected with Kenya-128B-15 and MP-12- strains (60 vs. 47%). However, only 2% of virus isolated from the salivary glands of Kenya-128B-15 and SA01-1322 co-infected mosquitoes represented reassortant genotypes. This was contrasted by 54% reassortment in the salivary glands of mosquitoes co-infected with Kenya-128B-15 and MP-12 strains. Furthermore, we observed preferential inclusion of genomic segments from the three parental strains among the reassorted viruses. Replication curves of select reassorted genotypes were significantly higher in Vero cells but not in Culex—derived cells. These data imply that mosquitoes play a crucial role in the reassortment of RVFV and potentially contribute to driving evolution of the virus. Full article
(This article belongs to the Special Issue Emerging Highlights in the Study of Rift Valley Fever Virus)
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14 pages, 954 KiB  
Article
Serological Evidence of Cryptic Rift Valley Fever Virus Transmission Among Humans and Livestock in Central Highlands of Kenya
by Silvia Situma, Evans Omondi, Luke Nyakarahuka, Raymond Odinoh, Marshal Mweu, Marianne W. Mureithi, Martin M. Mulinge, Erin Clancey, Jeanette Dawa, Isaac Ngere, Eric Osoro, Bronwyn Gunn, Limbaso Konongoi, Samoel A. Khamadi, Johan Michiels, Kevin K. Ariën, Barnabas Bakamutumaho, Robert F. Breiman and Kariuki Njenga
Viruses 2024, 16(12), 1927; https://doi.org/10.3390/v16121927 - 17 Dec 2024
Cited by 1 | Viewed by 1765
Abstract
Although the highlands of East Africa lack the geo-ecological landmarks of Rift Valley fever (RVF) disease hotspots to participate in cyclic RVF epidemics, they have recently reported growing numbers of small RVF clusters. Here, we investigated whether RVF cycling occurred among livestock and [...] Read more.
Although the highlands of East Africa lack the geo-ecological landmarks of Rift Valley fever (RVF) disease hotspots to participate in cyclic RVF epidemics, they have recently reported growing numbers of small RVF clusters. Here, we investigated whether RVF cycling occurred among livestock and humans in the central highlands of Kenya during inter-epidemic periods. A 2-year prospective hospital-based study among febrile patients (March 2022–February 2024) in Murang’a County of Kenya was followed by a cross-sectional human–animal survey. A total of 1468 febrile patients were enrolled at two clinics and sera tested for RVF virus RNA and antiviral antibodies. In the cross-sectional study, humans (n = 282) and livestock (n = 706) from randomly selected households were tested and questionnaire data were used to investigate sociodemographic and environmental risk factors by multivariate logistic regression. No human (n = 1750) or livestock (n = 706) sera tested positive for RVFV RNA. However, 4.4% livestock and 2.0% humans tested positive for anti-RVFV IgG, including 0.27% febrile patients who showed four-fold IgG increase and 2.4% young livestock (<12 months old), indicating recent virus exposure. Among humans, the odds of RVF exposure increased significantly (p < 0.05, 95% CI) in males (aOR: 4.77, 2.08–12.4), those consuming raw milk (aOR: 5.24, 1.13–17.9), milkers (aOR: 2.69, 1.23–6.36), and participants residing near quarries (aOR: 2.4, 1.08–5.72). In livestock, sheep and goats were less likely to be seropositive (aOR: 0.27, 0.12–0.60) than cattle. The increase in RVF disease activities in the highlands represents a widening geographic dispersal of the virus, and a greater risk of more widespread RVF epidemics in the future. Full article
(This article belongs to the Special Issue Emerging Highlights in the Study of Rift Valley Fever Virus)
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16 pages, 7075 KiB  
Article
Genomic Epidemiology of Rift Valley Fever Virus Involved in the 2018 and 2022 Outbreaks in Livestock in Rwanda
by Isidore Nsengimana, John Juma, Kristina Roesel, Methode N. Gasana, Fabrice Ndayisenga, Claude M. Muvunyi, Emmanuel Hakizimana, Jean N. Hakizimana, Gillian Eastwood, Augustino A. Chengula, Bernard Bett, Christopher J. Kasanga and Samuel O. Oyola
Viruses 2024, 16(7), 1148; https://doi.org/10.3390/v16071148 - 17 Jul 2024
Cited by 5 | Viewed by 3029
Abstract
Rift Valley fever (RVF), a mosquito-borne transboundary zoonosis, was first confirmed in Rwanda’s livestock in 2012 and since then sporadic cases have been reported almost every year. In 2018, the country experienced its first large outbreak, which was followed by a second one [...] Read more.
Rift Valley fever (RVF), a mosquito-borne transboundary zoonosis, was first confirmed in Rwanda’s livestock in 2012 and since then sporadic cases have been reported almost every year. In 2018, the country experienced its first large outbreak, which was followed by a second one in 2022. To determine the circulating virus lineages and their ancestral origin, two genome sequences from the 2018 outbreak, and thirty-six, forty-one, and thirty-eight sequences of small (S), medium (M), and large (L) genome segments, respectively, from the 2022 outbreak were generated. All of the samples from the 2022 outbreak were collected from slaughterhouses. Both maximum likelihood and Bayesian-based phylogenetic analyses were performed. The findings showed that RVF viruses belonging to a single lineage, C, were circulating during the two outbreaks, and shared a recent common ancestor with RVF viruses isolated in Uganda between 2016 and 2019, and were also linked to the 2006/2007 largest East Africa RVF outbreak reported in Kenya, Tanzania, and Somalia. Alongside the wild-type viruses, genetic evidence of the RVFV Clone 13 vaccine strain was found in slaughterhouse animals, demonstrating a possible occupational risk of exposure with unknown outcome for people working in meat-related industry. These results provide additional evidence of the ongoing wide spread of RVFV lineage C in Africa and emphasize the need for an effective national and international One Health-based collaborative approach in responding to RVF emergencies. Full article
(This article belongs to the Special Issue Emerging Highlights in the Study of Rift Valley Fever Virus)
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13 pages, 5975 KiB  
Article
Distinct Pathological Changes in Preweaning Mice Infected with Live-Attenuated Rift Valley Fever Virus Strains
by Cigdem Alkan, Eduardo Jurado-Cobena and Tetsuro Ikegami
Viruses 2024, 16(7), 999; https://doi.org/10.3390/v16070999 - 21 Jun 2024
Viewed by 1142
Abstract
Rift Valley fever (RVF) is a mosquito-borne zoonotic viral disease endemic to Africa and the Middle East. Live-attenuated RVF vaccines have been studied for both veterinary and human use due to their strong immunogenicity and cost-effective manufacturing. The live-attenuated MP-12 vaccine has been [...] Read more.
Rift Valley fever (RVF) is a mosquito-borne zoonotic viral disease endemic to Africa and the Middle East. Live-attenuated RVF vaccines have been studied for both veterinary and human use due to their strong immunogenicity and cost-effective manufacturing. The live-attenuated MP-12 vaccine has been conditionally approved for veterinary use in the U.S.A., and next-generation live-attenuated RVF vaccine candidates are being actively researched. Assessing the virulence phenotype of vaccine seeds or lots is crucial for managing vaccine safety. Previously, preweaning 19-day-old outbred CD1 mice have been used to evaluate the MP-12 strain. This study aimed to characterize the relative virulence of three live-attenuated RVF vaccine strains in 19-day-old inbred C57BL/6 mice: the recombinant MP-12 (rMP-12), the RVax-1, and the ∆NSs-∆NSm-rZH501 strains. Although this mouse model did not show dose-dependent pathogenesis, mice that succumbed to the infection exhibited distinct brain pathology. Mice infected with ∆NSs-∆NSm-rZH501 showed an infiltration of inflammatory cells associated with infected neurons, and focal lesions formed around virus-infected cells. In contrast, mice infected with rMP-12 or RVax-1 showed a minimal association of inflammatory cells in the brain, yet the virus spread diffusely. The preweaning model is likely useful for evaluating host responses to attenuated RVFV strains, although further refinement may be necessary to quantitate the virulence among different RVFV strains or vaccine lots. Full article
(This article belongs to the Special Issue Emerging Highlights in the Study of Rift Valley Fever Virus)
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14 pages, 4814 KiB  
Article
Safety and Efficacy upon Infection in Sheep with Rift Valley Fever Virus ZH548-rA2, a Triple Mutant Rescued Virus
by Sandra Moreno, Gema Lorenzo, Álvaro López-Valiñas, Nuria de la Losa, Celia Alonso, Elena Charro, José I. Núñez, Pedro J. Sánchez-Cordón, Belén Borrego and Alejandro Brun
Viruses 2024, 16(1), 87; https://doi.org/10.3390/v16010087 - 5 Jan 2024
Cited by 3 | Viewed by 2284
Abstract
The introduction of three single nucleotide mutations into the genome of the virulent RVFV ZH548 strain allows for the rescue of a fully attenuated virus in mice (ZH548-rA2). These mutations are located in the viral genes encoding the RdRp and the non-structural protein [...] Read more.
The introduction of three single nucleotide mutations into the genome of the virulent RVFV ZH548 strain allows for the rescue of a fully attenuated virus in mice (ZH548-rA2). These mutations are located in the viral genes encoding the RdRp and the non-structural protein NSs. This paper shows the results obtained after the subcutaneous inoculation of ZH548-rA2 in adult sheep and the subsequent challenge with the parental virus (ZH548-rC1). Inoculation with the ZH548-rA2 virus caused no detectable clinical or pathological effect in sheep, whereas inoculation of the parental rC1 virus caused lesions compatible with viral infection characterised by the presence of scattered hepatic necrosis. Viral infection was confirmed via immunohistochemistry, with hepatocytes within the necrotic foci appearing as the main cells immunolabelled against viral antigen. Furthermore, the inoculation of sheep with the rA2 virus prevented the liver damage expected after rC1 virus inoculation, suggesting a protective efficacy in sheep which correlated with the induction of both humoral and cell-mediated immune responses. Full article
(This article belongs to the Special Issue Emerging Highlights in the Study of Rift Valley Fever Virus)
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13 pages, 1603 KiB  
Article
Identification of Host Factors for Rift Valley Fever Phlebovirus
by Velmurugan Balaraman, Sabarish V. Indran, Yonghai Li, David A. Meekins, Laxmi U. M. R. Jakkula, Heidi Liu, Micheal P. Hays, Jayme A. Souza-Neto, Natasha N. Gaudreault, Philip R. Hardwidge, William C. Wilson, Friedemann Weber and Juergen A. Richt
Viruses 2023, 15(11), 2251; https://doi.org/10.3390/v15112251 - 13 Nov 2023
Cited by 1 | Viewed by 2962
Abstract
Rift Valley fever phlebovirus (RVFV) is a zoonotic pathogen that causes Rift Valley fever (RVF) in livestock and humans. Currently, there is no licensed human vaccine or antiviral drug to control RVF. Although multiple species of animals and humans are vulnerable to RVFV [...] Read more.
Rift Valley fever phlebovirus (RVFV) is a zoonotic pathogen that causes Rift Valley fever (RVF) in livestock and humans. Currently, there is no licensed human vaccine or antiviral drug to control RVF. Although multiple species of animals and humans are vulnerable to RVFV infection, host factors affecting susceptibility are not well understood. To identify the host factors or genes essential for RVFV replication, we conducted CRISPR-Cas9 knockout screening in human A549 cells. We then validated the putative genes using siRNA-mediated knock-downs and CRISPR-Cas9-mediated knock-out studies. The role of a candidate gene in the virus replication cycle was assessed by measuring intracellular viral RNA accumulation, and the virus titers were analyzed using plaque assay or TCID50 assay. We identified approximately 900 genes with potential involvement in RVFV infection and replication. Further evaluation of the effect of six genes on viral replication using siRNA-mediated knock-downs revealed that silencing two genes (WDR7 and LRP1) significantly impaired RVFV replication. For further analysis, we focused on the WDR7 gene since the role of the LRP1 gene in RVFV replication was previously described in detail. WDR7 knockout A549 cell lines were generated and used to dissect the effect of WRD7 on a bunyavirus, RVFV, and an orthobunyavirus, La Crosse encephalitis virus (LACV). We observed significant effects of WDR7 knockout cells on both intracellular RVFV RNA levels and viral titers. At the intracellular RNA level, WRD7 affected RVFV replication at a later phase of its replication cycle (24 h) when compared with the LACV replication, which was affected in an earlier replication phase (12 h). In summary, we identified WDR7 as an essential host factor for the replication of two different viruses, RVFV and LACV, both of which belong to the Bunyavirales order. Future studies will investigate the mechanistic role through which WDR7 facilitates phlebovirus replication. Full article
(This article belongs to the Special Issue Emerging Highlights in the Study of Rift Valley Fever Virus)
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Review

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25 pages, 1203 KiB  
Review
The Temperature-Associated Effects of Rift Valley Fever Virus Infections in Mosquitoes and Climate-Driven Epidemics: A Review
by Faustus A. Azerigyik, Shelby M. Cagle, William C. Wilson, Dana N. Mitzel and Rebekah C. Kading
Viruses 2025, 17(2), 217; https://doi.org/10.3390/v17020217 - 1 Feb 2025
Cited by 1 | Viewed by 1208
Abstract
Rift Valley fever virus (RVFV) is a mosquito-borne zoonotic disease within the genus Phlebovirus. Symptoms of the disease in animals range from moderate to severe febrile illness, which significantly impacts the livestock industry and causes severe health complications in humans. Similar to [...] Read more.
Rift Valley fever virus (RVFV) is a mosquito-borne zoonotic disease within the genus Phlebovirus. Symptoms of the disease in animals range from moderate to severe febrile illness, which significantly impacts the livestock industry and causes severe health complications in humans. Similar to bunyaviruses in the genus Orthobunyavirus transmitted by mosquitoes, RVFV progression is dependent on the susceptibility of the physical, cellular, microbial, and immune response barriers of the vectors. These barriers, shaped by the genetic makeup of the mosquito species and the surrounding environmental temperature, exert strong selective pressure on the virus, affecting its replication, evolution, and spread. The changing climate coupled with the aforementioned bottlenecks are significant drivers of RVF epidemics and expansion into previously nonendemic areas. Despite the link between microclimatic changes and RVF outbreaks, there is still a dearth of knowledge on how these temperature effects impact RVF transmission and vector competence and virus persistence during interepidemic years. This intricate interdependence between the virus, larval habitat temperatures, and vector competence necessitates increased efforts in addressing RVFV disease burden. This review highlights recent advancements made in response to shifting demographics, weather patterns, and conveyance of RVFV. Additionally, ongoing studies related to temperature-sensitive variations in RVFV–vector interactions and knowledge gaps are discussed. Full article
(This article belongs to the Special Issue Emerging Highlights in the Study of Rift Valley Fever Virus)
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