Search Results (22)

Mosquitoes serve as vectors for many arthropod-borne viruses (arboviruses) that are responsible for millions of human infections and thousands of deaths each year. Among these arboviruses, O’nyong-nyong virus (ONNV) is an African alphavirus mainly transmitted by Anopheles mosquitoes. ONNV can be detected through serological or molecular tests, the first showing cross-reactivity to co-circulating alphaviruses and requiring technically demanding confirmation, while the latter, usually based on real-time PCR, are costly and demand specific equipment. Isothermal amplification approaches, such as Loop-Mediated Isothermal Amplification (LAMP), should therefore provide a cost-effective, sensitive, and specific alternative for virus detection, suitable for the resource-limited regions where ONNV circulates up to the present time. Here, we describe the development and optimization of a rapid and highly sensitive (10 pfu/reaction) RT-LAMP assay for ONNV detection. Additionally, we demonstrate that it is possible to bypass the RNA extraction step, reducing sample handling time and costs. The final RT-LAMP_ONNV is a promising field detection tool for ONNV, enabling a better understanding of its impact and serving as a point-of-care diagnostic method. Full article

The first vaccine against chikungunya virus (CHIKV) was recently licensed in the U.S., Europe, and Canada (brand IXCHIQ^®, referred to as VLA1553). Other pathogenic alphaviruses co-circulate with CHIKV and major questions remain regarding the potential of IXCHIQ to confer cross-protection for populations that are exposed to them. Here, we characterized the cross-neutralizing antibody (nAb) responses against heterotypic CHIKV and additional arthritogenic alphaviruses in individuals at one month, six months, and one year post-IXCHIQ vaccination. We characterized nAbs against CHIKV strains LR2006, 181/25, and a 2021 isolate from Tocantins, Brazil, as well as O’nyong-nyong virus (ONNV), Mayaro virus (MAYV), and Ross River virus (RRV). IXCHIQ elicited 100% seroconversion to each virus, with the exception of RRV at 83.3% seroconversion of vaccinees, and cross-neutralizing antibody potency decreased with increasing genetic distance from CHIKV. We compared vaccinee responses to cross-nAbs elicited by natural CHIKV infection in individuals living in the endemic setting of Puerto Rico at 8–9 years post-infection. These data suggest that IXCHIQ efficiently and potently elicits cross-nAb breadth that extends to related alphaviruses in a manner similar to natural CHIKV infection, which may have important implications for individuals that are susceptible to alphavirus co-circulation in regions of potential vaccine rollout. Full article

The intracellular bacterium Wolbachia is increasingly being utilised in control programs to limit the spread of arboviruses by Aedes mosquitoes. Achieving a better understanding of how Wolbachia strains can reduce viral replication/spread could be important for the long-term success of such programs. Previous studies have indicated that for some strains of Wolbachia, perturbations in lipid metabolism and cholesterol storage are vital in Wolbachia-mediated antiviral activity against the flaviviruses dengue and Zika; however, it has not yet been examined whether arboviruses in the alphavirus group are affected in the same way. Here, using the reporters for the alphavirus Semliki Forest virus (SFV) in Aedes albopictus cells, we found that Wolbachia strains wMel, wAu and wAlbB blocked viral replication/translation early in infection and that storage of cholesterol in lipid droplets is not key to this inhibition. Another alphavirus, o’nyong nyong virus (ONNV), was tested in both Aedes albopictus cells and in vivo in stable, transinfected Aedes aegypti mosquito lines. The strains wMel, wAu and wAlbB show strong antiviral activity against ONNV both in vitro and in vivo. Again, 2-hydroxypropyl-β-cyclodextrin (2HPCD) was not able to rescue ONNV replication in cell lines, suggesting that the release of stored cholesterol caused by wMel is not able to rescue blockage of ONNV. Taken together, this study shows that alphaviruses appear to be inhibited early in replication/translation and that there may be differences in how alphaviruses are inhibited by Wolbachia in comparison to flaviviruses. Full article

During the past four decades, recurrent outbreaks of various arthropod-borne viruses have been reported in Mauritania. This review aims to consolidate the current knowledge on the epidemiology of the major arboviruses circulating in Mauritania. Online databases including PubMed and Web of Science were used to retrieve relevant published studies. The results showed that numerous arboviral outbreaks of variable magnitude occurred in almost all 13 regions of Mauritania, with Rift Valley fever (RVF), Crimean–Congo hemorrhagic fever (CCHF), and dengue (DEN) being the most common infections. Other arboviruses causing yellow fever (YF), chikungunya (CHIK), o’nyong-nyong (ONN), Semliki Forest (SF), West Nile fever (WNF), Bagaza (BAG), Wesselsbron (WSL), and Ngari (NRI) diseases have also been found circulating in humans and/or livestock in Mauritania. The average case fatality rates of CCHF and RVF were 28.7% and 21.1%, respectively. RVF outbreaks have often occurred after unusually heavy rainfalls, while CCHF epidemics have mostly been reported during the dry season. The central and southeastern regions of the country have carried the highest burden of RVF and CCHF. Sheep, cattle, and camels are the main animal reservoirs for the RVF and CCHF viruses. Culex antennatus and Cx. poicilipes mosquitoes and Hyalomma dromedarii, H. rufipes, and Rhipicephalus everesti ticks are the main vectors of these viruses. DEN outbreaks occurred mainly in the urban settings, including in Nouakchott, the capital city, and Aedes aegypti is likely the main mosquito vector. Therefore, there is a need to implement an integrated management strategy for the prevention and control of arboviral diseases based on sensitizing the high-risk occupational groups, such as slaughterhouse workers, shepherds, and butchers for zoonotic diseases, reinforcing vector surveillance and control, introducing rapid point-of-care diagnosis of arboviruses in high-risk areas, and improving the capacities to respond rapidly when the first signs of disease outbreak are identified. Full article

To estimate the prevalence of IgG antibodies against six arboviruses in people living with HIV-1 (PLWHIV) in Madagascar, we tested samples collected between January 2018 and June 2021. We used a Luminex-based serological assay to detect IgG antibodies against antigens from Dengue virus serotypes 1–4 (DENV1–4), Zika virus (ZIKV), West Nile virus (WNV), Usutu virus (USUV), Chikungunya virus (CHIKV), and O’nyong nyong virus (ONNV). Of the 1036 samples tested, IgG antibody prevalence was highest for ONNV (28.4%), CHIKV (26.7%), WNV-NS1 (27.1%), DENV1 (12.4%), USUV (9.9%), and DENV3 (8.9%). ZIKV (4.9%), DENV2 (4.6%), WNV-D3 (5.1%), and DENV4 (1.4%) were lower. These rates varied by province of origin, with the highest rates observed in Toamasina, on the eastern coast (50.5% and 56.8%, for CHIKV and ONNV, respectively). The seroprevalence increased with age for DENV1 and 3 (p = 0.006 and 0.038, respectively) and WNV DIII (p = 0.041). The prevalence of IgG antibodies against any given arborvirus varied over the year and significantly correlated with rainfalls in the different areas (r = 0.61, p = 0.036). Finally, we found a significant correlation between the seroprevalence of antibodies against CHIKV and ONNV and the HIV-1 RNA plasma viral load. Thus, PLWHIV in Madagascar are highly exposed to various arboviruses. Further studies are needed to explain some of our findings. Full article

Infection by arthritogenic alphaviruses (aavs) can lead to reactive arthritis, which is characterized by inflammation and persistence of the virus; however, its mechanisms remain ill-characterized. Intriguingly, it has been shown that viral persistence still takes place in spite of robust innate and adaptive immune responses, characterized notably by the infiltration of macrophages (sources of TNF-alpha) as well as T/NK cells (sources of IFN-gamma) in the infected joint. Aavs are known to target mesenchymal stem cells (MSCs) in the synovium, and we herein tested the hypothesis that the infection of MSCs may promote the expression of immunoregulators to skew the anti-viral cellular immune responses. We compared the regulated expression via human synovial MSCs of pro-inflammatory mediators (e.g., IL-1β, IL6, CCL2, miR-221-3p) to that of immunoregulators (e.g., IDO, TSG6, GAS6, miR146a-5p). We used human synovial tissue-derived MSCs which were infected with O’Nyong-Nyong alphavirus (ONNV, class II aav) alone, or combined with recombinant human TNF-α or IFN-γ, to mimic the clinical settings. We confirmed via qPCR and immunofluorescence that ONNV infected human synovial tissue-derived MSCs. Interestingly, ONNV alone did not regulate the expression of pro-inflammatory mediators. In contrast, IDO, TSG6, and GAS6 mRNA expression were increased in response to ONNV infection alone, but particularly when combined with both recombinant cytokines. ONNV infection equally decreased miR-146a-5p and miR-221-3p in the untreated cells and abrogated the stimulatory activity of the recombinant TNF-α but not the IFN-gamma. Our study argues for a major immunoregulatory phenotype of MSCs infected with ONNV which may favor virus persistence in the inflamed joint. Full article

Anopheles mosquitoes are the vectors of Plasmodium, the etiological agent of malaria. In addition, Anopheles funestus and Anopheles gambiae are the main vectors of the O’nyong-nyong virus. However, research on the viruses carried by Anopheles is scarce; thus, the possible transmission of viruses by Anopheles is still unexplored. This systematic review was carried out to identify studies that report viruses in natural populations of Anopheles or virus infection and transmission in laboratory-reared mosquitoes. The databases reviewed were EBSCO-Host, Google Scholar, Science Direct, Scopus and PubMed. After the identification and screening of candidate articles, a total of 203 original studies were included that reported on a variety of viruses detected in Anopheles natural populations. In total, 161 viruses in 54 species from 41 countries worldwide were registered. In laboratory studies, 28 viruses in 15 Anopheles species were evaluated for mosquito viral transmission capacity or viral infection. The viruses reported in Anopheles encompassed 25 viral families and included arboviruses, probable arboviruses and Insect-Specific Viruses (ISVs). Insights after performing this review include the need for (1) a better understanding of Anopheles-viral interactions, (2) characterizing the Anopheles virome—considering the public health importance of the viruses potentially transmitted by Anopheles and the significance of finding viruses with biological control activity—and (3) performing virological surveillance in natural populations of Anopheles, especially in the current context of environmental modifications that may potentiate the expansion of the Anopheles species distribution. Full article

O’nyong-nyong virus (ONNV) is a member of the reemerging arthritogenic alphaviruses that cause chronic debilitating polyarthralgia and/or polyarthritis via their tropism for the musculoskeletal system. Thus, the discovery of dual antiviral and anti-inflammatory drugs is a great challenge in this field. We investigated the effects of the common plant-derived alkaloids berberine (isoquinoline), matrine (quinolizidine), and tabersonine (indole) at a non-toxic concentration (10 μM) on a human fibroblast cell line (HS633T) infected by ONNV (MOI 1). Using qRT-PCR analyses, we measured the RNA levels of the gene coding for the viral proteins and for the host cell immune factors. These alkaloids demonstrated multifocal effects by the inhibition of viral replication, as well as the regulation of the type-I interferon antiviral signaling pathway and the inflammatory mediators and pathways. Berberine and tabersonine proved to be the more valuable compounds. The results supported the proposal that these common alkaloids may be useful scaffolds for drug discovery against arthritogenic alphavirus infection. Full article

The presence of alphaviruses, such as chikungunya virus (CHIKV), has never been reported in Mauritania. We assessed the seroprevalence of CHIKV among Nouakchott residents. A cross-sectional study involving 1300 non-febrile patients consulting at the Nouakchott hospital center was conducted between January and June 2021. The presence of anti-CHIKV IgG and neutralizing antibodies against CHIKV, O’nyong-nyong virus (ONNV), and Semliki Forest virus (SFV) was determined by an enzyme-linked immunosorbent assay (ELISA) and a serum neutralization test, respectively, and the associated risk factors were investigated. Of the 1300 study participants, serological evidence of previous exposure to CHIKV was observed in 37 individuals (2.8%). Sex, age, reported use of repellants, and bed net ownership and usage were not associated with CHIKV seropositivity. Our results showed the co-circulation of two other alphaviruses, ONNV and SFV, in Nouakchott in 30 (2.3%) individuals. This is the first study that documents the co-circulation of CHIKV, ONNV, and SFV in Mauritania, albeit at low prevalence. Surveillance and routine testing for alphaviruses and other arboviruses in symptomatic patients should be implemented in health facilities to assess the health burden associated with these viruses. Efforts should also be made to strengthen the vector control measures. Full article

Certain re-emerging alphaviruses, such as chikungunya virus (CHIKV), cause serious disease and widespread epidemics. To develop virus-specific therapies, it is critical to understand the determinants of alphavirus pathogenesis and virulence. One major determinant is viral evasion of the host interferon response, which upregulates antiviral effectors, including zinc finger antiviral protein (ZAP). Here, we demonstrated that Old World alphaviruses show differential sensitivity to endogenous ZAP in 293T cells: Ross River virus (RRV) and Sindbis virus (SINV) are more sensitive to ZAP than o’nyong’nyong virus (ONNV) and CHIKV. We hypothesized that the more ZAP-resistant alphaviruses evade ZAP binding to their RNA. However, we did not find a correlation between ZAP sensitivity and binding to alphavirus genomic RNA. Using a chimeric virus, we found the ZAP sensitivity determinant lies mainly within the alphavirus non-structural protein (nsP) gene region. Surprisingly, we also did not find a correlation between alphavirus ZAP sensitivity and binding to nsP RNA, suggesting ZAP targeting of specific regions in the nsP RNA. Since ZAP can preferentially bind CpG dinucleotides in viral RNA, we identified three 500-bp sequences in the nsP region where CpG content correlates with ZAP sensitivity. Interestingly, ZAP binding to one of these sequences in the nsP2 gene correlated to sensitivity, and we confirmed that this binding is CpG-dependent. Our results demonstrate a potential strategy of alphavirus virulence by localized CpG suppression to evade ZAP recognition. Full article

Introduction. Arboviruses and malaria pose a growing threat to public health, affecting not only the general population but also immunocompromised individuals and pregnant women. Individuals in vulnerable groups are at a higher risk of severe complications from the co-circulation and transmission of ZIKV, malaria, and FLAVI fever. In sub-Saharan countries, such as Nigeria, these mosquito-borne infections have clinical presentations that overlap with other diseases (dengue, West Nile virus, and Japanese encephalitis, chikungunya, and O’nyong o’nyong virus), making them a diagnostic challenge for clinicians in regions where they co-circulate. Vertical transmission can have a devastating impact on maternal health and fetal outcomes, including an increased risk of fetal loss and premature birth. Despite the global recognition of the burden of malaria and arboviruses, particularly ZIKV and other flaviviruses, there is limited data on their prevalence in Nigeria. In urban settings, where these diseases are endemic and share common biological, ecological, and economic factors, they may impact treatment outcomes and lead to epidemiological synergy. Hence, it is imperative to conduct sero-epidemiological and clinical studies to better understand the disease burden and hidden endemicity, thereby enabling improved prevention and clinical management. Method. Serum samples collected from outpatients between December 2020 and November 2021 in three regions of Nigeria were tested for the presence of IgG antibody seropositivity against ZIKV and FLAVI using immunoblot serological assay. Results. The overall cohort co-circulation antibody seropositivity of ZIKV, FLAVI and malaria was 24.0% (209/871). A total of 19.2% (167/871) of the study participants had ZIKV-seropositive antibodies and 6.2% (54/871) were FLAVI-seropositive, while 40.0% (348/871) of the subjects had malaria parasite antigens. Regional analysis revealed that participants from the southern region had the highest antibody seropositivity against ZIKV (21.7% (33/152)) and FLAVI (8.6% (13/152)), whereas those from the central region had a higher malaria parasite antigen (68.5% (287/419)). Conclusions. This study represents the largest comparative cross-sectional descriptive sero-epidemiological investigation of ZIKV-FLAVI and malaria cocirculation in Nigeria. The findings of this study revealed increased antibody seropositivity, hidden endemicity, and the burden of ZIKV, FLAVI, and malaria co-circulating in Nigeria. Full article

Mosquito-borne diseases caused by viruses and parasites are responsible for more than 700 million infections each year. Anopheles and Aedes are the two major vectors for, respectively, malaria and arboviruses. Anopheles mosquitoes are the primary vector of just one known arbovirus, the alphavirus o’nyong-nyong virus (ONNV), which is closely related to the chikungunya virus (CHIKV), vectored by Aedes mosquitoes. However, Anopheles harbor a complex natural virome of RNA viruses, and a number of pathogenic arboviruses have been isolated from Anopheles mosquitoes in nature. CHIKV and ONNV are in the same antigenic group, the Semliki Forest virus complex, are difficult to distinguish via immunodiagnostic assay, and symptomatically cause essentially the same human disease. The major difference between the arboviruses appears to be their differential use of mosquito vectors. The mechanisms governing this vector specificity are poorly understood. Here, we summarize intrinsic and extrinsic factors that could be associated with vector specificity by these viruses. We highlight the complexity and multifactorial aspect of vectorial specificity of the two alphaviruses, and evaluate the level of risk of vector shift by ONNV or CHIKV. Full article

The reservoir for zoonotic o’nyong-nyong virus (ONNV) has remained unknown since this virus was first recognized in Uganda in 1959. Building on existing evidence for mosquito blood-feeding on various frugivorous bat species in Uganda, and seroprevalence for arboviruses among bats in Uganda, we sought to assess if serum samples collected from bats in Uganda demonstrated evidence of exposure to ONNV or the closely related zoonotic chikungunya virus (CHIKV). In total, 652 serum samples collected from six bat species were tested by plaque reduction neutralization test (PRNT) for neutralizing antibodies against ONNV and CHIKV. Forty out of 303 (13.2%) Egyptian rousettes from Maramagambo Forest and 1/13 (8%) little free-tailed bats from Banga Nakiwogo, Entebbe contained neutralizing antibodies against ONNV. In addition, 2/303 (0.7%) of these Egyptian rousettes contained neutralizing antibodies to CHIKV, and 8/303 (2.6%) contained neutralizing antibodies that were nonspecifically reactive to alphaviruses. These data support the interepidemic circulation of ONNV and CHIKV in Uganda, although Egyptian rousette bats are unlikely to serve as reservoirs for these viruses given the inconsistent occurrence of antibody-positive bats. Full article

Several alphaviruses, such as chikungunya (CHIKV) and Onyong-nyong (ONNV), are endemic in Kenya and often cause outbreaks in different parts of the country. We assessed the seroprevalence of alphaviruses in patients with acute febrile illness in two geographically distant areas in Kenya with no previous record of alphavirus outbreaks. Blood samples were collected from febrile patients in health facilities located in the rural Taita-Taveta County in 2016 and urban Kibera informal settlement in Nairobi in 2017 and tested for CHIKV IgG and IgM antibodies using an in-house immunofluorescence assay (IFA) and a commercial ELISA test, respectively. A subset of CHIKV IgG or IgM antibody-positive samples were further analyzed using plaque reduction neutralization tests (PRNT) for CHIKV, ONNV, and Sindbis virus. Out of 537 patients, 4 (0.7%) and 28 (5.2%) had alphavirus IgM and IgG antibodies, respectively, confirmed on PRNT. We show evidence of previous and current exposure to alphaviruses based on serological testing in areas with no recorded history of outbreaks. Full article

Climate change, variability and anthropogenic forcings such as land use change are the main forcings of river discharge variability. However, an understanding of their simultaneous impacts on river discharge remains limited in some parts of the world. To shed light on this issue, the objective of this article is to investigate the effects of rainfall variability and land use change on river discharge in the Nyong basin (at Olama and Mbalmayo gauging stations) and some of its sub-basins (So’o and Mefou) over the long period 1950–2018. To achieve this goal, hydro-meteorological data of the Nyong basin and sub-basins were analyzed using the Pettitt test. Likewise, land use changes in the basin and sub-basins were also analyzed using supervised classifications of Landsat satellite images of the basins at different periods (1973, 2000 and 2018). On the annual scale, rainfall has decreased statistically over the studied basins. In the large basins (Olama and Mbalmayo), this decrease in rainfall is synchronous with that of discharges, while it is concomitant with an increase in the Mefou (small basin). After the ruptures within time series identified in the annual modules, the extreme discharges (maximum and minimum) decreased in Olama; in Mbalmayo, the maximum discharges remained stable while the minimum discharges decreased. On the other hand, the maximum and minimum discharges have significantly increased in the Mefou. The stability of maximum discharges at Mbalmayo and the increase in extremes on the Mefou in a context where the precipitation that generates the discharge has decreased can be attributed to land use change. These changes are essentially marked by an increase in impervious areas and a reduction in forest cover. On the seasonal scale, the impact of precipitation in the dry season is visible on the flows of the rainy seasons that follow them on the large basins (Olama and Mbalmayo). Between the decades 1970–1990 and 2000–2010, there was respectively a significant increase, then a decrease in summer precipitation, which impacted the autumn discharges in the same direction. Conversely, between the same intervals, there was a significant decrease, then a slight increase in winter precipitation. The impact of winter precipitation on the spring discharge is more visible during the first period only (1970–1990). During the second period, winter precipitation seems to have more of an impact on the runoff for the same season. In the Mefou sub-basin, the precipitation plays an essentially amplifying role in the increase in discharge in the seasons during which they occur. Those having experienced an increase, or a maintenance of precipitation (summer and spring) recorded the most significant increases in discharges. These results could be useful for long-term planning on the demand and use of water, as well as flood management in the basins Full article