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![Schematic diagram of Rift Valley Fever virus (electron micrograph from Linda Stannard [258]). (A color version of this figure is available online at www.vetres.org.)](profile/Brian-Bird/publication/49712248/figure/fig5/AS:668668887306242@1536434494147/Schematic-diagram-of-Rift-Valley-Fever-virus-electron-micrograph-from-Linda-Stannard.png)
Schematic diagram of Rift Valley Fever virus (electron micrograph from Linda Stannard [258]). (A color version of this figure is available online at www.vetres.org.)
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Rift Valley fever(RVF) virus is an arbovirus in the Bunyaviridae family that, from phylogenetic analysis, appears to have first emerged in the mid-19th century and was only identified at the beginning of the 1930's in the Rift Valley region of Kenya. Despite being an arbovirus with a relatively simple but temporally and geographically stable genome...
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... S segment utilizes the ambisense strategy to code for two proteins, the nucleoprotein N and a nonstructural protein called NSs [104]. The coding capacity of the genome is depicted in Figure 1. The general view that only the viral genome is incorporated into the mature particle has been revisited since a small but significant fraction of the antigenomes i.e. replicative inter- mediates have been detected in purified RVFV particles [123]. ...
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Rift Valley fever (RVF) virus is an arbovirus in the _Bunyaviridae_ family that, from phylogenetic analysis, appears to have first emerged in the mid-19th century and was only identified at the beginning of the 1930s in the Rift Valley region of Kenya. Despite being an arbovirus with a relatively simple but temporally and geographically stable genome...
Citations
... The negative sense M segment encodes a non-structural protein (NSm) and glycoprotein (Gn and Gc) genes. The S segment encodes the nucleoprotein (N) and non-structural (NSs) genes in an ambisense manner; NSs play a major role in innate immunity and interact with interferon signaling pathways [9,10]. A previous study of 198 isolates obtained over a 67-year period from numerous countries classified sequences into 15 lineages, A to O [11]. ...
Rift Valley fever (RVF) is a re-emerging vector-borne zoonosis with a high public health and veterinary impact. In West Africa, many lineages were previously detected, but since 2020, lineage H from South Africa has been the main cause of the outbreaks. In this study, clinical samples collected through national surveillance were screened for RVF virus (RVFV) acute infection by RT-PCR and IgM ELISA tests. Sequencing, genome mapping and in vitro phenotypic characterization in mammal cells were performed on RT-PCR positive samples in comparison with other epidemic lineages (G and C). Four RVFV human cases were detected in Senegal and the sequence analyses revealed that the strains belonged to lineage H. The in vitro kinetics and genome mapping showed different replication efficiency profiles for the tested RVFV lineages and non-conservative mutations, which were more common to lineage G or specific to lineage H. Our findings showed the re-emergence of lineage H in Senegal in 2022, its high viral replication efficiency in vitro and support the findings that genetic diversity affects viral replication. This study gives new insights into the biological properties of lineage H and calls for deeper studies to better assess its potential to cause a future threat in Senegal.
... Infections can result in abortions, fetal malformations, and acute lethal infections in neonates and juveniles [9,10]. Humans develop a febrile disease that can progress to a potentially fatal hemorrhagic condition and/or a neurological syndrome [11][12][13]. RVFV is mainly transmitted through RVFV-infected mosquito bites (predominantly by Aedes and Culex spp.) or by direct contact with infected animal blood and/or tissues [11,14,15]. Fifty mosquito species have been identified as potential vectors for RVFV, and 47 species have been demonstrated to be competent vectors for RVFV transmission in experimental studies [16,17]. ...
... Humans develop a febrile disease that can progress to a potentially fatal hemorrhagic condition and/or a neurological syndrome [11][12][13]. RVFV is mainly transmitted through RVFV-infected mosquito bites (predominantly by Aedes and Culex spp.) or by direct contact with infected animal blood and/or tissues [11,14,15]. Fifty mosquito species have been identified as potential vectors for RVFV, and 47 species have been demonstrated to be competent vectors for RVFV transmission in experimental studies [16,17]. ...
Rift Valley fever (RVF) in ungulates and humans is caused by a mosquito-borne RVF phlebovirus (RVFV). Live attenuated vaccines are used in livestock (sheep and cattle) to control RVF in endemic regions during outbreaks. The ability of two or more different RVFV strains to reassort when co-infecting a host cell is a significant veterinary and public health concern due to the potential emergence of newly reassorted viruses, since reassortment of RVFVs has been documented in nature and in experimental infection studies. Due to the very limited information regarding the frequency and dynamics of RVFV reassortment, we evaluated the efficiency of RVFV reassortment in sheep, a natural host for this zoonotic pathogen. Co-infection experiments were performed, first in vitro in sheep-derived cells, and subsequently in vivo in sheep. Two RVFV co-infection groups were evaluated: group I consisted of co-infection with two wild-type (WT) RVFV strains, Kenya 128B-15 (Ken06) and Saudi Arabia SA01-1322 (SA01), while group II consisted of co-infection with the live attenuated virus (LAV) vaccine strain MP-12 and a WT strain, Ken06. In the in vitro experiments, the virus supernatants were collected 24 h post-infection. In the in vivo experiments, clinical signs were monitored, and blood and tissues were collected at various time points up to nine days post-challenge for analyses. Cell culture supernatants and samples from sheep were processed, and plaque-isolated viruses were genotyped to determine reassortment frequency. Our results show that RVFV reassortment is more efficient in co-infected sheep-derived cells compared to co-infected sheep. In vitro, the reassortment frequencies reached 37.9% for the group I co-infected cells and 25.4% for the group II co-infected cells. In contrast, we detected just 1.7% reassortant viruses from group I sheep co-infected with the two WT strains, while no reassortants were detected from group II sheep co-infected with the WT and LAV strains. The results indicate that RVFV reassortment occurs at a lower frequency in vivo in sheep when compared to in vitro conditions in sheep-derived cells. Further studies are needed to better understand the implications of RVFV reassortment in relation to virulence and transmission dynamics in the host and the vector. The knowledge learned from these studies on reassortment is important for understanding the dynamics of RVFV evolution.
... Large outbreaks and epidemics are usually preceded by heavy rainfall and flooding, which provide ideal conditions for the mass reproduction of primary mosquito vector species, such as Aedes species, and an overall abundance of secondary mosquito vectors. RVFV has already shown to spread outside of endemic regions with devastating implications for public health and the economy [5,6]. ...
MicroRNAs (miRNAs) are small non-coding RNAs that regulate the post-transcriptional expression of target genes. Virus-encoded miRNAs play an important role in the replication of viruses, modulate gene expression in both the virus and host, and affect their persistence and immune evasion in hosts. This renders viral miRNAs as potential targets for therapeutic applications, especially against pathogenic viruses that infect humans and animals. Rift Valley fever virus (RVFV) is a mosquito-borne zoonotic RNA virus that causes severe disease in both humans and livestock. High mortality among newborn lambs and abortion storms are key characteristics of an RVF outbreak. To date, limited information is available on RVFV-derived miRNAs. In this study, computational methods were used to analyse the RVFV genome for putative pre-miRNA genes, which were then analysed for the presence of mature miRNAs. We detected 19 RVFV-encoded miRNAs and identified their potential mRNAs targets in sheep (Ovis aries), the most susceptible host. The identification of significantly enriched O. aries genes in association with RVFV miRNAs will help elucidate the molecular mechanisms underlying RVFV pathogenesis and potentially uncover novel drug targets for RVFV.
... Protection against RVFV in all animal species is conferred by neutralizing antibodies, which can be detected within the first week post-infection [7]. Nucleoproteins (N) induce high levels of IgG and IgM antibodies in RVFV and other bunyavirus infections, but there is no evidence that anti-N antibodies exhibit virus-neutralizing activity [8]. ...
... Transmission between animals by direct contact with infected tissues or fluids has been observed, together with iatrogenic route by use of infected needles used for vaccination, particularly in endemic regions with limited economic resources [7,19]. The infections in humans can occur by inhaling aerosols of infectious body fluids, and consumption of raw or unpasteurized milk has also been identified as a risk factor for RVFV infection [12]. ...
Rift Valley fever is a vector-borne zoonotic disease caused by the Rift Valley fever virus (Phlebovirus genus) listed among the eight pathogens included in the Bluepoint list by the WHO. The transmission is mainly vehicled by Aedes and Culex mosquito species. Symptoms of the disease are varied and non-specific, making clinical diagnosis often challenging, especially in the early stages. Due to the difficulty in distinguishing Rift Valley fever from other viral hemorrhagic fevers, as well as many other diseases that cause fever, an early diagnosis of the infection is important to limit its spread and to provide appropriate care to patients. To date, there is no validated point-of-care diagnostic tool. The virus can only be detected in the blood for a brief period, suggesting that molecular methods alone are not sufficient for case determination. For this, it is preferable to combine both molecular and serological tests. The wide distribution of competent vectors in non-endemic areas, together with global climate change, elicit the spread of RVFV to continents other than Africa, making surveillance activities vital to prevent or to limit the impact of human outbreaks and for a rapid identification of positive cases, making diagnosis a key factor for this achievement.
... In recent decades, arboviral epidemics with a high burden of neurological disease have occurred around the world, presenting a major biological threat to humans, livestock, and agriculture [1][2][3][4][5][6]. Rift Valley fever phlebovirus (RVFV; Phenuiviridae family, Phlebovirus genus) is a highly pathogenic mosquito-borne virus that can cause lethal disease in both humans and livestock, eliciting a wide range of clinical manifestations, including hepatitis, hemorrhagic syndrome, and encephalitis associated with various neurological symptoms [4]. ...
... In recent decades, arboviral epidemics with a high burden of neurological disease have occurred around the world, presenting a major biological threat to humans, livestock, and agriculture [1][2][3][4][5][6]. Rift Valley fever phlebovirus (RVFV; Phenuiviridae family, Phlebovirus genus) is a highly pathogenic mosquito-borne virus that can cause lethal disease in both humans and livestock, eliciting a wide range of clinical manifestations, including hepatitis, hemorrhagic syndrome, and encephalitis associated with various neurological symptoms [4]. Up to 17% of cases during some outbreaks display neurological symptoms, including headaches, neck stiffness, confusion, hallucinations, eye pain, and vision loss, and fatality rates among patients with neurologic manifestation of disease reach 50% [7][8][9]. ...
Rift Valley fever phlebovirus (RVFV) is a highly pathogenic mosquito-borne virus with bioweapon potential due to its ability to be spread by aerosol transmission. Neurological symptoms are among the worst outcomes of infection, and understanding of pathogenesis mechanisms within the brain is limited. RVFV is classified as an overlap select agent by the CDC and USDA; therefore, experiments involving fully virulent strains of virus are tightly regulated. Here, we present two methods for inactivation of live virus within samples derived from mouse microglia cells using commercially available kits for the preparation of cells for flow cytometry and RNA extraction. Using the flow cytometry protocol, we demonstrate key differences in the response of primary murine microglia to infection with fully virulent versus attenuated RVFV.
... It is endemic throughout sub-Saharan Africa [2], the Arabian Peninsula (Saudi Arabia and Yemen), and Mayotte [3,4]. RVFV can be naturally transmitted to and cause disease in several animal species such as cattle, sheep, goats, and camels [5][6][7]. We have recently shown that white-tailed deer are highly susceptible to experimental infection with RVFV [8]. ...
... We have recently shown that white-tailed deer are highly susceptible to experimental infection with RVFV [8]. RVF in livestock is characterized by abortion storms in pregnant ewes and pregnant cattle and up to 100% mortality in newborn animals [5][6][7]. In humans, RVFV infection may be subclinical or causes mild flu-like symptoms and sometimes severe disease with hepatitis, retinitis, and encephalitis [9,10] with a small number of cases being lethal [11]. ...
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.
... Similar findings have been observed in Kenya in a study that demonstrated a strong connotation between RVF infection and large numbers of animals and mosquitoes in the 2006/2007 RVF outbreaks in Kenya (Anyangu et al., 2010). High cattle density should be predicted to significantly influence RVF occurrence in the Ugandan cattle corridor, in which 46% of Uganda's livestock is raised (NEPAD-CAADP, 2012), since cattle, sheep and goats are the principal animal host of RVFV (Pepin et al., 2010b). Several studies have linked RVF outbreaks to above-normal rainfall as this is a prerequisite for mosquito emergence (Anyamba et al., 2001;Bird et al., 2009;Anyamba et al., 2010;Linthicum et al., 2016). ...
... While knowledge of risk factors entails correct implementation of preventative measures it is hampered by cultural behaviors such as drinking raw milk/blood, especially among pastoralist communities in Kenya [15,21,40] and Tanzania [35]. While the shedding of the virus into milk is thought to be low, blood has been reported to be viraemic and highly infectious [6]. Presence of bushy vegetation and flooding are also important risk vectors for RVF outbreaks. ...
Rift Valley fever (RVF) is a mosquito-borne viral hemorrhagic disease that affects humans and livestock. In Kenya, the disease has spread to new areas like Baringo County, with a growing realization that the epidemiology of the virus may also include endemic transmission. Local knowledge of a disease in susceptible communities is a major driver of prevention and control efforts. A cross-sectional survey using a semi-structured questionnaire was conducted in five locations of Baringo South that had reported RVF cases during the last outbreak, to determine the knowledge, attitude and perception of the predominantly agro-pastoralist community to RVF. Knowledge of RVF clinical signs, transmission, risk factors and prevention all contributed to the total knowledge score. Additionally, the respondents’ attitude was based on their awareness of the threat posed by RVF and preparedness to take appropriate measures in case of suspected infection. Out of the 300 respondents, 80% had heard about the disease, however, only 9.6% attained at least half of the total knowledge score on RVF. Nevertheless, 86% recognized the threat it posed and knew the appropriate action to take in suspected human and livestock cases (positive attitude). Factors significantly associated with a better knowledge of RVF included higher education level, being Maasai, higher socio-economic index, old age and history of RVF in household members and livestock. Being Maasai and a higher socio-economic index were significantly associated with a positive attitude. The low level of knowledge exhibited by the respondents could be due to progressive loss of interest and information associated with a prolonged inter-outbreak period. This calls for regular awareness campaigns. More emphasis should also be put on educating communities on the role played by the mosquito vector in the epidemiology of RVF. The most promising routes of disseminating this information are radio and community gatherings.
... It is transmitted by mosquitoes, particularly those of the Aedes and Culex genera, and causes a range of clinical manifestations, including severe fever, hemorrhagic fever, and encephalitis. RVFV poses a significant threat to both animal health and human populations, particularly in regions where livestock farming is prevalent.105 The monitoring of viral load in RVFV infection is crucial as high viral loads have been linked to more severe clinical presentations, such as hemorrhagic fever, encephalitis, and multiorgan dysfunction. ...
The concept of viral load was introduced in the 1980s to measure the amount of viral genetic material in a person's blood, primarily for human immunodeficiency virus (HIV). It has since become crucial for monitoring HIV infection progression and assessing the efficacy of antiretroviral therapy. However, during the coronavirus disease 2019 pandemic, the term “viral load” became widely popularized, not only for the scientific community but for the general population. Viral load plays a critical role in both clinical patient management and research, providing valuable insights for antiviral treatment strategies, vaccination efforts, and epidemiological control measures. As measuring viral load is so important, why don't researchers discuss the best way to do it? Is it simply acceptable to use raw Ct values? Relying solely on Ct values for viral load estimation can be problematic due to several reasons. First, Ct values can vary between different quantitative polymerase chain reaction assays, platforms, and laboratories, making it difficult to compare data across studies. Second, Ct values do not directly measure the quantity of viral particles in a sample and they can be influenced by various factors such as initial viral load, sample quality, and assay sensitivity. Moreover, variations in viral RNA extraction and reverse-transcription steps can further impact the accuracy of viral load estimation, emphasizing the need for careful interpretation of Ct values in viral load assessment. Interestingly, we did not observe scientific articles addressing different strategies to quantify viral load. The absence of standardized and validated methods impedes the implementation of viral load monitoring in clinical management. The variability in cell quantities within samples and the variation in viral particle numbers within infected cells further challenge accurate viral load measurement and interpretation. To advance the field and improve patient outcomes, there is an urgent need for the development and validation of tailored, standardized methods for precise viral load quantification.
... This virus is maintained in nature through horizontal transmission between vertebrate hosts and blood-feeding mosquitoes and vertically, through infected mosquitoes and their offspring (Lumley et al., 2017). Transmission to humans occurs either through bites by a broad range of RVFV-infected mosquito species, mainly from the Aedes and Culex genera (Lumley et al., 2017), or through direct contact with body fluids, blood or tissues of viremic animals (Balenghien et al., 2013;Bird et al., 2009;Pepin et al., 2010). RVFV infection is associated with high rates of abortions among pregnant domestic ruminants (mainly sheep, goats and cattle) and can induce a high case fatality rate (CFR) up to 100% in newborn ruminants (Bird et al., 2009). ...
... RVFV infection is associated with high rates of abortions among pregnant domestic ruminants (mainly sheep, goats and cattle) and can induce a high case fatality rate (CFR) up to 100% in newborn ruminants (Bird et al., 2009). In humans, RVFV infection usually leads to a transient febrile illness with occasional complications that can progress to haemorrhagic syndrome and/or encephalitis which can lead to death (Ikegami & Makino, 2011;Pepin et al., 2010). ...
... In such context, RVFV infection may be either missed or misdiagnosed, and even outbreaks are underreported (Grossi-Soyster & Labeaud, 2020). Although many countries are considered free from RVFV, the international trade of domestic ruminants as well as the presence of known and potentially competent vectors in those countries might provide a suitable environment for the spread of RVFV from endemic to non-endemic countries (Bird et al., 2009;Pepin et al., 2010). Therefore, up-to-date knowledge of RVFV circulation, ecology, amplifying vertebrate hosts and vectors in specific regions and/or populations are critical for the design, evaluation and optimization of RVF surveillance and control programmes. ...
Rift Valley fever (RVF) is a severe zoonotic mosquito‐borne disease that represents an important threat to human and animal health, with major public health and socioeconomic impacts. This disease is endemic throughout many African countries and the Arabian Peninsula. This systematic review with meta‐analysis was conducted to determine the RVF prevalence in humans, mosquitoes and other animal species in Africa. The review also provides contemporary data on RVF case fatality rate (CFR) in humans. In this systematic review with meta‐analysis, a comprehensive literature search was conducted on the PubMed, Embase, Web of Science and Global Index Medicus databases from January 2000 to June 2022 to identify relevant studies. Pooled CFR and prevalence estimates were calculated using the random‐effects model. Subgroup analysis and sensitivity analysis were performed, and the I²‐statistic was used to investigate a potential source of heterogeneity. A total of 205 articles were included in the final analysis. The overall RVF CFR in humans was found to be 27.5% [95% CI = 8.0–52.5]. The overall pooled prevalence was 7.8% [95% CI = 6.2–9.6] in humans and 9.3% [95% CI = 8.1–10.6] in animals, respectively. The RVF prevalence in individual mosquitoes ranged from 0.0% to 25%. Subgroup analysis showed substantial heterogeneity with respect to geographical regions and human categories. The study shows that there is a correspondingly similar prevalence of RVF in human and animals; however, human CFR is much higher than the observed prevalence. The lack of a surveillance programme and the fact that this virus has subclinical circulation in animals and humans could explain these observations. The implementation of a One Health approach for RVF surveillance and control would be of great interest for human and animal health.
