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1.
Viruses ; 14(4)2022 04 09.
Article in English | MEDLINE | ID: mdl-35458511

ABSTRACT

BACKGROUND: Studies have linked bats to outbreaks of viral diseases in human populations such as SARS-CoV-1 and MERS-CoV and the ongoing SARS-CoV-2 pandemic. METHODS: We carried out a longitudinal survey from August 2020 to July 2021 at two sites in Zimbabwe with bat-human interactions: Magweto cave and Chirundu farm. A total of 1732 and 1866 individual bat fecal samples were collected, respectively. Coronaviruses and bat species were amplified using PCR systems. RESULTS: Analysis of the coronavirus sequences revealed a high genetic diversity, and we identified different sub-viral groups in the Alphacoronavirus and Betacoronavirus genus. The established sub-viral groups fell within the described Alphacoronavirus sub-genera: Decacovirus, Duvinacovirus, Rhinacovirus, Setracovirus and Minunacovirus and for Betacoronavirus sub-genera: Sarbecoviruses, Merbecovirus and Hibecovirus. Our results showed an overall proportion for CoV positive PCR tests of 23.7% at Chirundu site and 16.5% and 38.9% at Magweto site for insectivorous bats and Macronycteris gigas, respectively. CONCLUSIONS: The higher risk of bat coronavirus exposure for humans was found in December to March in relation to higher viral shedding peaks of coronaviruses in the parturition, lactation and weaning months of the bat populations at both sites. We also highlight the need to further document viral infectious risk in human/domestic animal populations surrounding bat habitats in Zimbabwe.


Subject(s)
Alphacoronavirus , COVID-19 , Chiroptera , Animals , COVID-19/epidemiology , Evolution, Molecular , Female , Genome, Viral , Phylogeny , SARS-CoV-2/genetics , Zimbabwe/epidemiology
2.
Infect Genet Evol ; 98: 105204, 2022 03.
Article in English | MEDLINE | ID: mdl-34999003

ABSTRACT

Mammarenaviruses have been a growing concern for public health in Africa since the 1970s when Lassa virus cases in humans were first described in west Africa. In southern Africa, a single outbreak of Lujo virus was reported to date in South Africa in 2008 with a case fatality rate of 80%. The natural reservoir of Lassa virus is Mastomys natalensis while for the Lujo virus the natural host has yet to be identified. Mopeia virus was described for the first time in M. natalensis in the central Mozambique in 1977 but few studies have been conducted in the region. In this study, rodents were trapped between March and November 2019in villages, croplands fields and mopane woodland forest. The aim was to assess the potential circulation and to evaluate the genetic diversity of mammarenaviruses in M. natalensis trapped in the Limpopo National Park and its buffer zone in Massingir district, Mozambique. A total of 534 M. natalensis were screened by RT-PCR and the overall proportion of positive individuals was 16.9%. No significant differences were detected between the sampled habitats (χ2 = 0.018; DF = 1; p = 0.893). The Mopeia virus (bootstrap value 91%) was the Mammarenavirus circulating in the study area sites, forming a specific sub-clade with eight different sub-clusters. We concluded that Mopeia virus circulates in all habitats investigated and it forms a different sub-clade to the one reported in central Mozambique in 1977.


Subject(s)
Arenaviridae Infections/veterinary , Arenaviridae/isolation & purification , Murinae , Rodent Diseases/epidemiology , Animals , Arenaviridae Infections/epidemiology , Ecosystem , Mozambique/epidemiology , Parks, Recreational
3.
Viruses ; 13(11)2021 11 03.
Article in English | MEDLINE | ID: mdl-34835018

ABSTRACT

Mayaro virus (MAYV) is an emergent alphavirus that causes MAYV fever. It is often associated with debilitating symptoms, particularly arthralgia and myalgia. MAYV infection is becoming a considerable health issue that, unfortunately, lacks a specific antiviral treatment. Favipiravir, a broad-spectrum antiviral drug, has recently been shown to exert anti-MAYV activity in vitro. In the present study, the potential of Favipiravir to inhibit MAYV replication in an in vivo model was evaluated. Immunocompetent mice were orally administrated 300 mg/kg/dose of Favipiravir at pre-, concurrent-, or post-MAYV infection. The results showed a significant reduction in infectious viral particles and viral RNA transcripts in the tissues and blood of the pre- and concurrently treated infected mice. A significant reduction in the presence of both viral RNA transcript and infectious viral particles in the tissue and blood of pre- and concurrently treated infected mice was observed. By contrast, Favipiravir treatment post-MAYV infection did not result in a reduction in viral replication. Interestingly, Favipiravir strongly decreased the blood levels of the liver disease markers aspartate- and alanine aminotransferase in the pre- and concurrently treated MAYV-infected mice. Taken together, these results suggest that Favipiravir is a potent antiviral drug when administered in a timely manner.


Subject(s)
Alphavirus Infections/drug therapy , Alphavirus/drug effects , Amides/pharmacology , Antiviral Agents/pharmacology , Pyrazines/pharmacology , Alanine Transaminase/drug effects , Alphavirus Infections/virology , Animals , Aspartate Aminotransferases/drug effects , Cell Line , Chlorocebus aethiops , Disease Models, Animal , Female , Liver , Mice , Mice, Inbred C57BL , Vero Cells , Virus Replication/drug effects
4.
Viruses ; 13(3)2021 03 11.
Article in English | MEDLINE | ID: mdl-33799906

ABSTRACT

Mayaro virus (MAYV) and chikungunya virus (CHIKV) are known for their arthrotropism, but accumulating evidence shows that CHIKV infections are occasionally associated with serious neurological complications. However, little is known about the capacity of MAYV to invade the central nervous system (CNS). We show that human neural progenitors (hNPCs), pericytes and astrocytes are susceptible to MAYV infection, resulting in the production of infectious viral particles. In primary astrocytes, MAYV, and to a lesser extent CHIKV, elicited a strong antiviral response, as demonstrated by an increased expression of several interferon-stimulated genes, including ISG15, MX1 and OAS2. Infection with either virus led to an enhanced expression of inflammatory chemokines, such as CCL5, CXCL10 and CXCL11, whereas MAYV induced higher levels of IL-6, IL-12 and IL-15 in these cells. Moreover, MAYV was more susceptible than CHIKV to the antiviral effects of both type I and type II interferons. Taken together, this study shows that although MAYV and CHIKV are phylogenetically related, they induce different types of antiviral responses in astrocytes. This work is the first to evaluate the potential neurotropism of MAYV and shows that brain cells and particularly astrocytes and hNPCs are permissive to MAYV, which, consequently, could lead to MAYV-induced neuropathology.


Subject(s)
Alphavirus Infections/immunology , Alphavirus/immunology , Astrocytes/immunology , Astrocytes/virology , Brain/immunology , 2',5'-Oligoadenylate Synthetase/metabolism , Alphavirus Infections/pathology , Animals , Brain/virology , Cell Line , Chemokine CCL5/metabolism , Chemokine CXCL10/metabolism , Chemokine CXCL11/metabolism , Chikungunya Fever/immunology , Chikungunya virus/immunology , Chlorocebus aethiops , Cytokines/metabolism , Humans , Interferon Type I/immunology , Interferon-gamma/immunology , Myxovirus Resistance Proteins/metabolism , Neural Stem Cells/virology , Pericytes/virology , Ubiquitins/metabolism , Vero Cells
5.
Viruses ; 12(12)2020 11 24.
Article in English | MEDLINE | ID: mdl-33255243

ABSTRACT

Based on a large study conducted on wild great ape fecal samples collected in regions of Gabon where previous human outbreaks of Ebola virus disease have occurred between 1994 and 2002, we provide evidence for prevalence of Zaire ebolavirus (EBOV)-specific antibodies of 3.9% (immunoglobulin G (IgG)) and 3.5% (immunoglobulin M (IgM)) in chimpanzees and 8.8% (IgG) and 2.4% (IgM) in gorillas. Importantly, we observed a high local prevalence (31.2%) of anti-EBOV IgG antibodies in gorilla samples. This high local rate of positivity among wild great apes raises the question of a spatially and temporally localized increase in EBOV exposure risk and the role that can be played by these animals as sentinels of the virus's spread or reemergence in a given area.


Subject(s)
Ape Diseases/immunology , Ape Diseases/virology , Ebolavirus , Gorilla gorilla/immunology , Gorilla gorilla/virology , Hemorrhagic Fever, Ebola/veterinary , Animals , Antibodies, Viral , Ape Diseases/diagnosis , Ape Diseases/epidemiology , Feces/virology , Gabon/epidemiology , Geography , Immunoglobulin G/immunology , Immunoglobulin M/immunology , Pan troglodytes/immunology , RNA, Viral , Sequence Analysis, DNA
6.
Parasit Vectors ; 13(1): 313, 2020 Jun 16.
Article in English | MEDLINE | ID: mdl-32546281

ABSTRACT

BACKGROUND: The Onchocercidae is a family of filarial nematodes with several species of medical or veterinary importance. Microfilariae are found in the blood and/or the dermis and are usually diagnosed in humans by microscopy examination of a blood sample or skin biopsy. The main objectives of this study were to evaluate whether filariae DNA can be detected in faecal samples of wild non-human primates (NHPs), whether the detected parasites were closely related to those infecting humans and whether filarial DNA detection in faeces is associated with co-infections with nematodes (Oesophagostumum sp. and Necator sp.) known to cause blood loss while feeding on the host intestinal mucosa. METHODS: A total of 315 faecal samples from 6 species of NHPs from Cameroon and Gabon were analysed. PCRs targeted DNA fragments of cox1 and 12S rDNA genes, to detect the presence of filariae, and the internal transcribed spacer 2 (ITS2), to detect the presence of Oesophagostomum sp. and Necator sp. infections. RESULTS: Among the 315 samples analysed, 121 produced sequences with > 90% homology with Onchocercidae reference sequences. However, 63% of the 12S rDNA and 78% of the cox1 gene sequences were exploitable for phylogenetic analyses and the amplification of the 12S rDNA gene showed less discriminating power than the amplification of the cox1 fragment. Phylogenetic analyses showed that the cox1 sequences obtained from five chimpanzee DNA faecal samples from Gabon and two from Cameroon cluster together with Mansonella perstans with high bootstrap support. Most of the remaining sequences clustered together within the genus Mansonella, but the species could not be resolved. Among the NHP species investigated, a significant association between filarial DNA detection and Oesophagostomum sp. and Necator sp. infection was observed only in gorillas. CONCLUSIONS: To our knowledge, this is the first study reporting DNA from Mansonella spp. in faecal samples. Our results raise questions about the diversity and abundance of these parasites in wildlife, their role as sylvatic reservoirs and their potential for zoonotic transmission. Future studies should focus on detecting variants circulating in both human and NHPs, and improve the molecular information to resolve or support taxonomy classification based on morphological descriptions.


Subject(s)
Feces/parasitology , Mansonella/genetics , Mansonelliasis/veterinary , Necator/classification , Oesophagostomum/classification , Primates/parasitology , Animals , Cameroon , Cyclooxygenase 1/genetics , DNA, Helminth/genetics , Dried Blood Spot Testing , Gabon , Genotype , Necator/genetics , Oesophagostomum/genetics , Phylogeny
7.
BMC Infect Dis ; 20(1): 49, 2020 Jan 15.
Article in English | MEDLINE | ID: mdl-31941464

ABSTRACT

BACKGROUND: Hepatitis B is a major concern in Africa, especially in HIV-infected patients. Unfortunately, access to hepatitis B virus (HBV) testing and adequate treatment remains a challenge in the continent. We investigated HBV testing, treatment, and virologic suppression in HIV-infected patients followed up as part of Cameroon's national antiretroviral programme. METHODS: A cross-sectional survey was performed in adult patients receiving antiretroviral therapy (ART) in 19 hospitals in the Centre and Littoral regions in Cameroon. The proportions of patients tested for hepatitis B surface antigen (HBsAg) prior to the study were compared among all study hospitals using the Chi-square test. The association of individual and hospital-related characteristics with HBV testing and virologic suppression was assessed using multilevel logistic regression models. RESULTS: Of 1706 patients (women 74%, median age 42 years, median time on ART 3.9 years), 302 (17.7%) had been tested for HBsAg prior to the study. The proportion of HBV-tested patients ranged from 0.8 to 72.5% according to the individual hospital (p < 0.001). HBV testing was lower in women (adjusted odds ratio [aOR] 0.64, 95% confidence interval [CI] 0.46-0.89, p = 0.010) and higher in patients who initiated ART in 2010 or later (aOR 1.66, 95% CI 1.23-2.27, p < 0.001). Of 159 HBsAg-positive patients at the time of the study (9.3%), only 97 (61.0%) received Tenofovir + Lamivudine (or Emtricitabine). Of 157 coinfected patients, 114 (72.6%) had a HBV viral load < 10 IU/mL. HBV suppression was higher in patients with a HIV viral load < 300 copies/mL (aOR 3.46, 95% CI 1.48-8.09, p = 0.004) and lower in patients with increased ALT level (aOR 0.86 per 10 IU/mL increase, 95% CI 0.75-0.97, p = 0.019). CONCLUSIONS: A substantial proportion of HIV/HBV coinfected patients were at higher risk of liver disease progression. Improving the management of HBV infection in the routine healthcare setting in Africa is urgently required in order to achieve the 2030 elimination targets. Micro-elimination of HBV infection in people living with HIV could be an easier and cost-effective component than more widely scaling up HBV policies.


Subject(s)
Coinfection/drug therapy , HIV Infections/drug therapy , Hepatitis B virus/genetics , Hepatitis B/drug therapy , Hepatitis B/virology , Sustained Virologic Response , Adult , Anti-Retroviral Agents/therapeutic use , Cameroon , Cross-Sectional Studies , Female , Follow-Up Studies , Genotype , Hepatitis B Surface Antigens/blood , Humans , Male , Middle Aged , Public Health , Viral Load
8.
Viruses ; 11(12)2019 11 28.
Article in English | MEDLINE | ID: mdl-31795197

ABSTRACT

Viruses belonging to the Dicistroviridae family have attracted a great deal of attention from scientists owing to their negative impact on agricultural economics, as well as their recent identification as potential aetiological agents of febrile illness in human patients. On the other hand, some Dicistroviruses are also studied for their potential biopesticide properties. To date, Dicistrovirus characterized in African mainland remain scarce. By using High-Throughput Sequencing technology on insectivorous bat faeces (Hipposideros Caffer) sampled in a cave used by humans to collect bat guano (bat manure) as fertilizer in Zimbabwe, we characterized the full-length sequences of three Dicistrovirus belonging to the Cripavirus and Aparavirus genus: Big Sioux River Virus-Like (BSRV-Like), Acute Bee Paralysis Virus (ABPV), and Aphid Lethal Paralysis Virus (ALPV). Phylogenetic analyses of ORF-1 and ORF-2 genes showed a complex evolutionary history between BSRV and close viruses, as well as for the Aparavirus genus. Herewith, we provide the first evidence of the presence of Dicistrovirus in Zimbabwe and highlight the need to further document the impact of such viruses on crops, as well as in beekeeping activities in Zimbabwe which represent a crucial source of income for Zimbabwean people.


Subject(s)
Chiroptera/virology , Crops, Agricultural/virology , Dicistroviridae/genetics , Agriculture , Animals , Biological Evolution , Dicistroviridae/isolation & purification , Feces/virology , High-Throughput Nucleotide Sequencing , Humans , Phylogeny , Sequence Analysis, RNA , Zimbabwe
9.
Viruses ; 11(10)2019 10 09.
Article in English | MEDLINE | ID: mdl-31601017

ABSTRACT

Mayaro (MAYV) is an emerging arthropod-borne virus belonging to the Alphavirus genus of the Togaviridae family. Although forest-dwelling Haemagogus mosquitoes have been considered as its main vector, the virus has also been detected in circulating Aedes ssp mosquitoes. Here we assess the susceptibility of Aedes aegypti and Aedes albopictus to infection with MAYV and their innate immune response at an early stage of infection. Aedes albopictus was more susceptible to infection with MAYV than Ae. aegypti. Analysis of transcript levels of twenty immunity-related genes by real-time PCR in the midgut of both mosquitoes infected with MAYV revealed increased expression of several immune genes, including CLIP-domain serine proteases, the anti-microbial peptides defensin A, E, cecropin E, and the virus inducible gene. The regulation of certain genes appeared to be Aedes species-dependent. Infection of Ae. aegypti with MAYV resulted in increased levels of myeloid differentiation2-related lipid recognition protein (ML26A) transcripts, as compared to Ae. albopictus. Increased expression levels of thio-ester-containing protein 22 (TEP22) and Niemann-Pick type C1 (NPC1) gene transcripts were observed in infected Ae. albopictus, but not Ae. aegypti. The differences in these gene expression levels during MAYV infection could explain the variation in susceptibility observed in both mosquito species.


Subject(s)
Aedes/virology , Alphavirus Infections/transmission , Alphavirus/immunology , Immunity, Innate , Aedes/immunology , Animals , Antimicrobial Cationic Peptides/genetics , Antimicrobial Cationic Peptides/metabolism , Gene Expression/immunology , Gene Expression Profiling , Immunity, Innate/genetics , Mosquito Vectors/virology , Real-Time Polymerase Chain Reaction , Serine Proteases/genetics , Serine Proteases/metabolism
10.
Viruses ; 11(9)2019 08 29.
Article in English | MEDLINE | ID: mdl-31470617

ABSTRACT

Mayaro virus (MAYV) is an emerging arthritogenic alphavirus belonging to the Togaviridae family. Infection leads to a dengue-like illness accompanied by severe polyarthralgia. However, the molecular and cellular mechanisms of arthritis as a result of MAYV infection remain poorly understood. In the present study, we assess the susceptibility of human chondrocytes (HC), fibroblast-like synoviocytes and osteoblasts that are the major cell types involved in osteoarthritis, to infection with MAYV. We show that these cells are highly permissive to MAYV infection and that viral RNA copy number and viral titers increase over time in infected cells. Knowing that HC are the primary cells in articular cartilage and are essential for maintaining the cartilaginous matrix, gene expression studies were conducted in MAYV-infected primary HC using polymerase chain reaction (PCR) arrays. The infection of the latter cells resulted in an induction in the expression of several matrix metalloproteinases (MMP) including MMP1, MMP7, MMP8, MMP10, MMP13, MMP14 and MMP15 which could be involved in the destruction of articular cartilage. Infected HC were also found to express significantly increased levels of various IFN-stimulated genes and arthritogenic mediators such as TNF-α and IL-6. In conclusion, MAYV-infected primary HC overexpress arthritis-related genes, which may contribute to joint degradation and pathogenesis.


Subject(s)
Alphavirus Infections/virology , Alphavirus/physiology , Arthritis/genetics , Chondrocytes/virology , Alphavirus/immunology , Alphavirus Infections/genetics , Alphavirus Infections/immunology , Cell Adhesion/genetics , Cell Survival , Cells, Cultured , Chondrocytes/immunology , Cytokines/genetics , Cytokines/metabolism , Extracellular Matrix/genetics , Gene Expression Profiling , Humans , Matrix Metalloproteinases/genetics , Osteoblasts/virology , RNA, Viral/metabolism , Synoviocytes/virology
11.
PLoS One ; 14(8): e0221179, 2019.
Article in English | MEDLINE | ID: mdl-31415663

ABSTRACT

Dengue fever is caused by dengue viruses (DENV) from the Flavivirus genus and is the most prevalent arboviral disease. DENV exists in four immunogenically distinct and genetically-related serotypes (DENV-1 to 4), each subdivided in genotypes. Despite the endemicity of all four DENV serotypes in Thailand, no prior study has characterized the circulation of DENV in the southern provinces of the country. To determine the genetic diversity of DENV circulating in Southern Thailand in 2015 and 2016, we investigated 46 viruses from 182 patients' sera confirmed positive for DENV by serological and Nested RT-PCR tests. Our dataset included 2 DENV-1, 20 DENV-2, 9 DENV-3 and 15 DENV-4. Phylogenetic analysis was performed on viral envelop sequences. This revealed that part of the identified genotypes from DENV-1 and DENV-4 had been predominant in Asia (genotype I for both serotypes), while genotype II for DENV-4 and the Cosmopolitan genotype DENV-2 were also circulating. Whereas DENV-3 genotype II had been predominantly detected in South East Asia during the previous decades, we found genotype III and genotype I in Southern Thailand. All DENV genotype identified in this study were closely related to contemporary strains circulating in Southeast Asian countries, emphasizing the regional circulation of DENV. These results provide new insights into the co-circulation of all four DENV serotypes in Southern Thailand, confirming the hyperendemicity of DENV in the region. These findings also suggest a new trend of dissemination for some DENV serotypes with a possible shift in genotype distribution; as recently observed in other Asian countries.


Subject(s)
Dengue Virus/genetics , Dengue/genetics , Genotype , Phylogeny , Serogroup , Adolescent , Adult , Child , Coculture Techniques , Dengue/epidemiology , Dengue Virus/isolation & purification , Female , Humans , Male , Middle Aged , Polymerase Chain Reaction , Reverse Transcriptase Polymerase Chain Reaction , Thailand/epidemiology
12.
Int J Mol Sci ; 20(7)2019 Apr 05.
Article in English | MEDLINE | ID: mdl-30959732

ABSTRACT

Chikungunya virus (CHIKV) and Zika virus (ZIKV) are emerging arboviruses that pose a worldwide threat to human health. Currently, neither vaccine nor antiviral treatment to control their infections is available. As the skin is a major viral entry site for arboviruses in the human host, we determined the global proteomic profile of CHIKV and ZIKV infections in human skin fibroblasts using Stable Isotope Labelling by Amino acids in Cell culture (SILAC)-based mass-spectrometry analysis. We show that the expression of the interferon-stimulated proteins MX1, IFIT1, IFIT3 and ISG15, as well as expression of defense response proteins DDX58, STAT1, OAS3, EIF2AK2 and SAMHD1 was significantly up-regulated in these cells upon infection with either virus. Exogenous expression of IFITs proteins markedly inhibited CHIKV and ZIKV replication which, accordingly, was restored following the abrogation of IFIT1 or IFIT3. Overexpression of SAMHD1 in cutaneous cells, or pretreatment of cells with the virus-like particles containing SAMHD1 restriction factor Vpx, resulted in a strong increase or inhibition, respectively, of both CHIKV and ZIKV replication. Moreover, silencing of SAMHD1 by specific SAMHD1-siRNA resulted in a marked decrease of viral RNA levels. Together, these results suggest that IFITs are involved in the restriction of replication of CHIKV and ZIKV and provide, as yet unreported, evidence for a proviral role of SAMHD1 in arbovirus infection of human skin cells.


Subject(s)
Chikungunya virus/physiology , Fibroblasts/metabolism , Fibroblasts/virology , SAM Domain and HD Domain-Containing Protein 1/metabolism , Skin/pathology , Virus Replication/physiology , Zika Virus/physiology , Cell Line , Chikungunya Fever/virology , Humans , Molecular Sequence Annotation , Protein Interaction Maps , Proteolysis , Up-Regulation , Viral Regulatory and Accessory Proteins/metabolism , Zika Virus Infection/virology
13.
Viruses ; 10(10)2018 10 09.
Article in English | MEDLINE | ID: mdl-30304789

ABSTRACT

The maintenance mechanisms of ebolaviruses in African forest ecosystems are still unknown, but indirect evidences point at the involvement of some bat species. Despite intense research, the main bat-maintenance hypothesis has not been confirmed yet. The alternative hypotheses of a non-bat maintenance host or a maintenance community including, or not, several bat and other species, deserves more investigation. However, African forest ecosystems host a large biodiversity and abound in potential maintenance hosts. How does one puzzle out? Since recent studies have revealed that several bat species have been exposed to ebolaviruses, the common denominator to these hypotheses is that within the epidemiological cycle, some bats species must be exposed to the viruses and infected by these potential alternative hosts. Under this constraint, and given the peculiar ecology of bats (roosting behaviour, habitat utilisation, and flight mode), we review the hosts and transmission pathways that can lead to bat exposure and infection to ebolaviruses. In contrast to the capacity of bats to transmit ebolaviruses and other pathogens to many hosts, our results indicate that only a limited number of hosts and pathways can lead to the transmission of ebolaviruses to bats, and that the alternative maintenance host, if it exists, must be amongst them. A list of these pathways is provided, along with protocols to prioritise and investigate these alternative hypotheses. In conclusion, taking into account the ecology of bats and their known involvement in ebolaviruses ecology drastically reduces the list of potential alternative maintenance hosts for ebolaviruses. Understanding the natural history of ebolaviruses is a health priority, and investigating these alternative hypotheses could complete the current effort focused on the role of bats.


Subject(s)
Chiroptera/virology , Disease Reservoirs/virology , Ebolavirus/isolation & purification , Hemorrhagic Fever, Ebola/virology , Africa , Animals , Ebolavirus/classification , Ebolavirus/genetics , Ebolavirus/physiology , Hemorrhagic Fever, Ebola/transmission , Humans , Zoonoses/transmission , Zoonoses/virology
14.
PLoS One ; 13(10): e0206093, 2018.
Article in English | MEDLINE | ID: mdl-30359409

ABSTRACT

Zika virus (ZIKV) is an emerging arbovirus of the Flaviviridae family. Although infection with ZIKV generally leads to mild disease, its recent emergence in the Americas has been associated with an increase in the development of the Guillain-Barré syndrome in adults, as well as with neurological complications, in particular congenital microcephaly, in new-borns. To date, little information is available on neuroinflammation induced by ZIKV, notably in microglial cells in the context of their metabolic activity, a series of chemical transformations that are essential for their growth, reproduction, structural maintenance and environmental responses. Therefore, in the present study we investigated the metabolomic profile of ZIKV-infected microglia. Microglial cells were exposed to ZIKV at different time points and were analyzed by a Liquid Chromatography-High Resolution mass spectrometry-based metabolomic approach. The results show that ZIKV infection in microglia leads to modulation of the expression of numerous metabolites, including lysophospholipids, particulary Lysophosphatidylcholine, and phospholipids such as Phosphatidylcholine, Phosphatidylserine, Ceramide and Sphingomyelin, and carboxylicic acids as Undecanedioic and Dodecanedioic acid. Some of these metabolites are involved in neuronal differentiation, regulation of apoptosis, virion architecture and viral replication. ZIKV infection was associated with concomitant secretion of inflammatory mediators linked with central nervous system inflammation such as IL-6, TNF-α, IL-1ß, iNOS and NO. It also resulted in the upregulation of the expression of the gene encoding CX3CR1, a chemokine receptor known to regulate functional synapse plasticity and signaling between microglial cells. These findings highlight an important role for microglia and their metabolites in the process of neuroinflammation that occurs during ZIKV pathogenesis.


Subject(s)
Metabolome/physiology , Microglia/metabolism , Zika Virus Infection/metabolism , Animals , Cells, Cultured , Chlorocebus aethiops , Culicidae , Fetus/cytology , Fetus/virology , Humans , Metabolomics , Microcephaly/metabolism , Microcephaly/pathology , Microglia/pathology , Vero Cells , Virus Replication/physiology , Zika Virus/physiology , Zika Virus Infection/pathology
15.
Infect Genet Evol ; 58: 253-257, 2018 03.
Article in English | MEDLINE | ID: mdl-29331670

ABSTRACT

Bats carry a great diversity of zoonotic viruses with a high-impact on human health and livestock. Since the emergence of new coronaviruses and paramyxoviruses in humans (e.g. Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) and Nipah virus), numerous studies clearly established that bats can maintain some of these viruses. Improving our understanding on the role of bats in the epidemiology of the pathogens they harbour is necessary to prevent cross-species spill over along the wild/domestic/human gradient. In this study, we screened bat faecal samples for the presence of Coronavirus and Paramyxovirus in two caves frequently visited by local people to collect manure and/or to hunt bats in Zimbabwe. We amplified partial RNA-dependent RNA polymerase genes of Alpha and Betacoronavirus together with the partial polymerase gene of Paramyxovirus. Identified coronaviruses were related to pathogenic human strains and the paramyxovirus belonged to the recently described Jeilongvirus genus. Our results highlighted the importance of monitoring virus circulation in wildlife, especially bats, in the context of intense human-wildlife interfaces in order to strengthen prevention measures among local populations and to implement sentinel surveillance in sites with high zoonotic diseases transmission potential.


Subject(s)
Alphacoronavirus/genetics , Betacoronavirus/genetics , Chiroptera/virology , Coronavirus Infections/veterinary , Paramyxoviridae Infections/veterinary , Paramyxoviridae/genetics , Alphacoronavirus/classification , Animals , Betacoronavirus/classification , Communicable Diseases, Emerging/veterinary , Evolution, Molecular , Genetic Variation , Genome, Viral , Paramyxoviridae/classification , Phylogeny , Zimbabwe
16.
Infect Genet Evol ; 55: 68-70, 2017 11.
Article in English | MEDLINE | ID: mdl-28866137

ABSTRACT

Chikungunya virus (CHIKV) transmission occurs through the bite of an infected Aedes mosquito which injects virus-containing saliva into the skin of the human host during blood feeding. In the present study, we have determined the effect of Aedes aegypti saliva on CHIKV replication in human skin fibroblasts, a major cell type for viral entry, which mimics the events that occur during natural transmission. A significant increase in the expression of viral transcripts and infectious viral particles was observed in fibroblasts infected with CHIKV in the presence of saliva, as compared with those infected with virus alone. CHIKV-infected human fibroblasts were found to express significantly increased levels of various type I IFN-responsive genes, as demonstrated by specific PCR array analysis. In contrast, the expression of these genes was markedly decreased in cells infected with CHIKV in the presence of mosquito saliva. Moreover, Western blotting analysis revealed that STAT2 and its phosphorylated form were down-regulated in the presence of mosquito saliva. Our data demonstrate for the first time the significance of Aedes aegypti saliva in promoting CHIKV infection via down-regulation of several type I IFN-responsive genes in infected human skin fibroblasts via the JAK-STAT signaling pathway.


Subject(s)
Aedes/virology , Chikungunya Fever/metabolism , Chikungunya Fever/virology , Chikungunya virus/physiology , Interferon Type I/metabolism , Saliva/virology , Signal Transduction , Virus Replication , Animals , Cells, Cultured , Chikungunya Fever/genetics , Chikungunya Fever/transmission , Fibroblasts/metabolism , Fibroblasts/virology , Gene Expression Regulation , Humans
17.
Sci Rep ; 7(1): 3145, 2017 06 09.
Article in English | MEDLINE | ID: mdl-28600536

ABSTRACT

Chikungunya virus (CHIKV) is an emerging arbovirus of the Togaviridae family that poses a present worldwide threat to human in the absence of any licensed vaccine or antiviral treatment to control viral infection. Here, we show that compounds interfering with intracellular cholesterol transport have the capacity to inhibit CHIKV replication in human skin fibroblasts, a major viral entry site in the human host. Pretreatment of these cells with the class II cationic amphiphilic compound U18666A, or treatment with the FDA-approved antidepressant drug imipramine resulted in a near total inhibition of viral replication and production at the highest concentration used without any cytotoxic effects. Imipramine was found to affect both the fusion and replication steps of the viral life cycle. The key contribution of cholesterol availability to the CHIKV life cycle was validated further by the use of fibroblasts from Niemann-Pick type C (NPC) patients in which the virus was unable to replicate. Interestingly, imipramine also strongly inhibited the replication of several Flaviviridae family members, including Zika, West Nile and Dengue virus. Together, these data show that this compound is a potential drug candidate for anti-arboviral treatment.


Subject(s)
Chikungunya virus/drug effects , Cholesterol/metabolism , Imipramine/pharmacology , Skin/virology , Androstenes/pharmacology , Biological Transport/drug effects , Cells, Cultured , Fibroblasts/cytology , Fibroblasts/virology , Humans , Niemann-Pick Disease, Type C/pathology , Skin/cytology , Skin/drug effects , Virus Internalization/drug effects , Virus Replication/drug effects
18.
PLoS One ; 12(1): e0169067, 2017.
Article in English | MEDLINE | ID: mdl-28081564

ABSTRACT

Enteroviruses (EVs) belong to the family Picornaviridae and are responsible for mild to severe diseases in mammals including humans and non-human primates (NHP). Simian EVs were first discovered in the 1950s in the Old World Monkeys and recently in wild chimpanzee, gorilla and mandrill in Cameroon. In the present study, we screened by PCR EVs in 600 fecal samples of wild apes and monkeys that were collected at four sites in Gabon. A total of 32 samples were positive for EVs (25 from mandrills, 7 from chimpanzees, none from gorillas). The phylogenetic analysis of VP1 and VP2 genes showed that EVs identified in chimpanzees were members of two human EV species, EV-A and EV-B, and those identified in mandrills were members of the human species EV-B and the simian species EV-J. The identification of two novel enterovirus types, EV-B112 in a chimpanzee and EV-B113 in a mandrill, suggests these NHPs could be potential sources of new EV types. The identification of EV-B107 and EV90 that were previously found in humans indicates cross-species transfers. Also the identification of chimpanzee-derived EV110 in a mandrill demonstrated a wide host range of this EV. Further research of EVs in NHPs would help understanding emergence of new types or variants, and evaluating the real risk of cross-species transmission for humans as well for NHPs populations.


Subject(s)
Ape Diseases , Enterovirus Infections , Enterovirus , Gorilla gorilla/virology , Mandrillus/virology , Pan troglodytes/virology , Phylogeny , Animals , Ape Diseases/genetics , Ape Diseases/virology , Enterovirus/genetics , Enterovirus/isolation & purification , Enterovirus Infections/genetics , Enterovirus Infections/veterinary , Enterovirus Infections/virology , Humans
19.
Infect Genet Evol ; 49: 134-137, 2017 04.
Article in English | MEDLINE | ID: mdl-28095299

ABSTRACT

ZIKA virus (ZIKV) is a newly emerging arbovirus. Since its discovery 60years ago in Uganda, it has spread throughout the Pacific, Latin America and the Caribbean, emphasizing the capacity of ZIKV to spread to non-endemic regions worldwide. Although infection with ZIKV often leads to mild disease, its recent emergence in the Americas has coincided with an increase in adults developing Guillain-Barré syndrome and neurological complications in new-borns, such as congenital microcephaly. Many questions remain unanswered regarding the complications caused by different primary isolates of ZIKV. Here, we report the permissiveness of primary human astrocytes for two clinically relevant, Asian and African ZIKV strains and show that both isolates strongly induce antiviral immune responses in these cells albeit with markedly different kinetics. This study describes for the first time the specific antiviral gene expression in infected primary human astrocytes, the major glial cells within the central nervous system.


Subject(s)
Astrocytes/immunology , DEAD Box Protein 58/immunology , Host-Pathogen Interactions , NLR Proteins/immunology , Toll-Like Receptors/immunology , Astrocytes/virology , DEAD Box Protein 58/genetics , Gene Expression Regulation , Humans , Immunity, Innate , NLR Proteins/genetics , Primary Cell Culture , RNA, Viral/biosynthesis , RNA, Viral/genetics , Receptors, Immunologic , Time Factors , Toll-Like Receptors/genetics , Viral Load/immunology , Virus Replication/immunology , Zika Virus/genetics , Zika Virus/growth & development
20.
J Virol ; 91(6)2017 03 15.
Article in English | MEDLINE | ID: mdl-28077632

ABSTRACT

Human immunodeficiency virus type 1 (HIV-1) is the result of cross-species transmission of simian immunodeficiency virus from chimpanzees (SIVcpz). SIVcpz is a chimeric virus which shares common ancestors with viruses infecting red-capped mangabeys and a subset of guenon species. The epidemiology of SIV infection in hominoids is characterized by low prevalences and an uneven geographic distribution. Surveys in Cameroon indicated that two closely related members of the guenon species subset, mustached guenons and greater spot-nosed guenons, infected with SIVmus and SIVgsn, respectively, also have low rates of SIV infections in their populations. Compared to that for other monkeys, including red-capped mangabeys and closely related guenon species, such an epidemiology is unusual. By intensifying sampling of geographically distinct populations of mustached and greater spot-nosed guenons in Gabon and including large sample sets of mona guenons from Cameroon, we add strong support to the hypothesis that the paucity of SIV infections in wild populations is a general feature of this monophyletic group of viruses. Furthermore, comparative phylogenetic analysis reveals that this phenotype is a feature of this group of viruses infecting phylogenetically disparate hosts, suggesting that this epidemiological phenotype results from infection with these HIV-1-related viruses rather than from a common host factor. Thus, these HIV-1-related viruses, i.e., SIVcpz and the guenon viruses which share an ancestor with part of the SIVcpz genome, have an epidemiology distinct from that found for SIVs in other African primate species.IMPORTANCE Stable virus-host relationships are established over multiple generations. The prevalence of viral infections in any given host is determined by various factors. Stable virus-host relationships of viruses that are able to cause persistent infections and exist with high incidences of infection are generally characterized by a lack of morbidity prior to host reproduction. Such is the case for cytomegalovirus (CMV) and Epstein-Barr virus (EBV) infections of humans. SIV infections of most African primate species also satisfy these criteria, with these infections found at a high prevalence and with rare cases of clinical disease. In contrast, SIVcpz, the ancestor of HIV-1, has a different epidemiology, and it has been reported that infected animals suffer from an AIDS-like disease in the wild. Here we conclusively demonstrate that viruses which are closely related to SIVcpz and infect a subset of guenon monkeys show an epidemiology resembling that of SIVcpz.


Subject(s)
Genetic Variation , Phylogeography , Simian Acquired Immunodeficiency Syndrome/epidemiology , Simian Acquired Immunodeficiency Syndrome/virology , Simian Immunodeficiency Virus/classification , Simian Immunodeficiency Virus/genetics , Topography, Medical , Animals , Cameroon , Gabon , Haplorhini , Prevalence , Simian Immunodeficiency Virus/isolation & purification
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