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Emerging Microbes & Infections Dec 2024Identification of the diverse animal hosts responsible for spill-over events from animals to humans is crucial for comprehending the transmission patterns of emerging...
Identification of the diverse animal hosts responsible for spill-over events from animals to humans is crucial for comprehending the transmission patterns of emerging infectious diseases, which pose significant public health risks. To better characterize potential animal hosts of Lassa virus (LASV), we assessed domestic and non-domestic animals from 2021-2022 in four locations in southern Nigeria with reported cases of Lassa fever (LF). Birds, lizards, and domestic mammals (dogs, pigs, cattle and goats) were screened using RT-qPCR, and whole genome sequencing was performed for lineage identification on selected LASV positive samples. Animals were also screened for exposure to LASV by enzyme-linked immunosorbent assay (ELISA). Among these animals, lizards had the highest positivity rate by PCR. Genomic sequencing of samples in most infected animals showed sub-lineage 2 g of LASV. Seropositivity was highest among cattle and lowest in pigs. Though the specific impact these additional hosts may have in the broader virus-host context are still unknown - specifically relating to pathogen diversity, evolution, and transmission - the detection of LASV in non-rodent hosts living in proximity to confirmed human LF cases suggests their involvement during transmission as potential reservoirs. Additional epidemiological data comparing viral genomes from humans and animals, as well as those circulating within the environment will be critical in understanding LASV transmission dynamics and will ultimately guide the development of countermeasures for this zoonotic health threat.
Topics: Humans; Animals; Cattle; Dogs; Swine; Lassa virus; Lassa Fever; Nigeria; Genome, Viral; Public Health; Mammals
PubMed: 38088796
DOI: 10.1080/22221751.2023.2294859 -
PLoS Neglected Tropical Diseases Nov 2023Lassa fever (Lf) is a viral haemorrhagic disease endemic to West Africa and is caused by the Lassa mammarenavirus. The rodent Mastomys natalensis serves as the primary...
Lassa fever (Lf) is a viral haemorrhagic disease endemic to West Africa and is caused by the Lassa mammarenavirus. The rodent Mastomys natalensis serves as the primary reservoir and its ecology and behaviour have been linked to the distinct spatial and temporal patterns in the incidence of Lf. Nigeria has experienced an unprecedented epidemic that lasted from January until April of 2018, which has been followed by subsequent epidemics of Lf in the same period every year since. While previous research has modelled the case seasonality within Nigeria, this did not capture the seasonal variation in the reproduction of the zoonotic reservoir and its effect on case numbers. To this end, we introduce an approximate Bayesian computation scheme to fit our model to the case data from 2018-2020 supplied by the NCDC. In this study we used a periodically forced seasonal nonautonomous system of ordinary differential equations as a vector model to demonstrate that the population dynamics of the rodent reservoir may be responsible for the spikes in the number of observed cases in humans. The results show that in December through to March, spillover from the zoonotic reservoir drastically increases and spreads the virus to the people of Nigeria. Therefore to effectively combat Lf, attention and efforts should be concentrated during this period.
Topics: Animals; Humans; Lassa Fever; Nigeria; Incidence; Bayes Theorem; Lassa virus; Murinae
PubMed: 37956170
DOI: 10.1371/journal.pntd.0011543 -
West African Journal of Medicine Jul 2023Lassa fever is an acute hemorrhagic viral disease caused by the Lassa virus. The Lassa virus belongs to the Arenaviridae family of RNA viruses. On 05/04/2016; two cases...
BACKGROUND
Lassa fever is an acute hemorrhagic viral disease caused by the Lassa virus. The Lassa virus belongs to the Arenaviridae family of RNA viruses. On 05/04/2016; two cases of Lassa fever were reported from Katsina State with the date of presentation of the first case on 23/03/2016 and 27/03/ 2016 for the second case. We investigated the outbreak to identify the agent and the source and propose recommendations as well as to assess the practice of infection, prevention and control (IPC).
METHODS
We used descriptive study to describe contact tracing and facility assessment. We described the outbreak by time, place, and person. We defined a case using established guidelines and line-listed the contacts. We conducted IPC facility check in the state. Blood specimens were collected for Lassa fever detection. Microsoft Excel and Epi-info version 7.1.6 were used for data analysis.
RESULTS
The index case of Lassa fever in Katsina State was seen on 23/03/2016 with a travel history from Kaduna State. The second case had contact with a positive Lassa fever case from Gwagwalada, Federal Capital Territory (FCT). A total of 82 contacts were line listed (9 developed Lassa fever). The case fatality rate was 27.3%. IPC checklist revealed 37.5% of the health facilities lacked personal protective equipment and safety boxes, 25% lacked isolation wards, and none had chlorine solution. Overall, 61% of personnel had poor knowledge of Lassa fever, 31% had fair knowledge and 8% had good knowledge.
CONCLUSION
A multiple-source epidemic with sources of primary infection from outside Katsina state was noted. Most of the health facilities assessed lack basic IPC materials and knowledge on Lassa fever which should be addressed.
Topics: Humans; Lassa Fever; Nigeria; Disease Outbreaks; Lassa virus; Epidemics
PubMed: 37515581
DOI: No ID Found -
Viruses Aug 2023There is no specific chemotherapy approved for the treatment of pathogenic arenaviruses that cause severe hemorrhagic fever (HF) in the population of endemic regions in...
There is no specific chemotherapy approved for the treatment of pathogenic arenaviruses that cause severe hemorrhagic fever (HF) in the population of endemic regions in America and Africa. The present study reports the effects of the natural flavonoid quercetin (QUER) on the infection of A549 and Vero cells with Junín virus (JUNV), agent of the Argentine HF. By infectivity assays, a very effective dose-dependent reduction of JUNV multiplication was shown by cell pretreatment at 2-6 h prior to the infection at non-cytotoxic concentrations, with 50% effective concentration values in the range of 6.1-7.5 µg/mL. QUER was also active by post-infection treatment but with minor efficacy. Mechanistic studies indicated that QUER mainly affected the early steps of virus adsorption and internalization in the multiplication cycle of JUNV. Treatment with QUER blocked the phosphorylation of Akt without changes in the total protein expression, detected by Western blot, and the consequent perturbation of the PI3K/Akt pathway was also associated with the fluorescence redistribution from membrane to cytoplasm of TfR1, the cell receptor recognized by JUNV. Then, it appears that the cellular antiviral state, induced by QUER treatment, leads to the prevention of JUNV entry into the cell.
Topics: Chlorocebus aethiops; Animals; Quercetin; Flavonoids; Phosphatidylinositol 3-Kinases; Proto-Oncogene Proteins c-akt; Vero Cells; Arenaviridae Infections; Arenavirus
PubMed: 37632083
DOI: 10.3390/v15081741 -
European Journal of Immunology Aug 2023Previous studies that used peptide-MHC (pMHC) tetramers (tet) to identify self-specific T cells have questioned the effectiveness of thymic-negative selection. Here, we...
Previous studies that used peptide-MHC (pMHC) tetramers (tet) to identify self-specific T cells have questioned the effectiveness of thymic-negative selection. Here, we used pMHCI tet to enumerate CD8 T cells specific for the immunodominant gp33 epitope of lymphocytic choriomeningitis virus glycoprotein (GP) in mice transgenically engineered to express high levels of GP as a self-antigen in the thymus. In GP-transgenic mice (GP ), monoclonal P14 TCR CD8 T cells that express a GP-specific TCR could not be detected by gp33/D -tet staining, indicative of their complete intrathymic deletion. By contrast, in the same GP mice, substantial numbers of polyclonal CD8 T cells identifiable by gp33/D -tet were present. The gp33-tet staining profiles of polyclonal T cells from GP and GP-negative (GP ) mice were overlapping, but mean fluorescence intensities were ∼15% lower in cells from GP mice. Remarkably, the gp33-tet T cells in GP mice failed to clonally expand after lymphocytic choriomeningitis virus infection, whereas those of GP mice did so. In Nur77 -reporter mice, dose-dependent responses to gp33 peptide-induced TCR stimulation revealed that gp33-tet T cells with high ligand sensitivity are lacking in GP mice. Hence, pMHCI tet staining identifies self-specific CD8 T cells but tends to overestimate the number of truly self-reactive cells.
Topics: Mice; Animals; Viral Proteins; Antigens, Viral; Receptors, Antigen, T-Cell; CD8-Positive T-Lymphocytes; Mice, Transgenic; Glycoproteins; Lymphocytic choriomeningitis virus; Peptides; Mice, Inbred C57BL
PubMed: 37179469
DOI: 10.1002/eji.202350402 -
Journal of Immunology (Baltimore, Md. :... Feb 2024SHP-1 (Src homology region 2 domain-containing phosphatase 1) is a well-known negative regulator of T cells, whereas its close homolog SHP-2 is the long-recognized main...
SHP-1 (Src homology region 2 domain-containing phosphatase 1) is a well-known negative regulator of T cells, whereas its close homolog SHP-2 is the long-recognized main signaling mediator of the PD-1 inhibitory pathway. However, recent studies have challenged the requirement of SHP-2 in PD-1 signaling, and follow-up studies further questioned the alternative idea that SHP-1 may replace SHP-2 in its absence. In this study, we systematically investigate the role of SHP-1 alone or jointly with SHP-2 in CD8+ T cells in a series of gene knockout mice. We show that although SHP-1 negatively regulates CD8+ T cell effector function during acute lymphocytic choriomeningitis virus (LCMV) infection, it is dispensable for CD8+ T cell exhaustion during chronic LCMV infection. Moreover, in contrast to the mortality of PD-1 knockout mice upon chronic LCMV infection, mice double deficient for SHP-1 and SHP-2 in CD8+ T cells survived without immunopathology. Importantly, CD8+ T cells lacking both phosphatases still differentiate into exhausted cells and respond to PD-1 blockade. Finally, we found that SHP-1 and SHP-2 suppressed effector CD8+ T cell expansion at the early and late stages, respectively, during chronic LCMV infection.
Topics: Animals; Mice; CD8-Positive T-Lymphocytes; Lymphocytic Choriomeningitis; Lymphocytic choriomeningitis virus; Mice, Inbred C57BL; Mice, Knockout; Programmed Cell Death 1 Receptor; T-Cell Exhaustion
PubMed: 38088801
DOI: 10.4049/jimmunol.2300462 -
Ecology Letters Nov 2023Zoonotic diseases threaten human health worldwide and are often associated with anthropogenic disturbance. Predicting how disturbance influences spillover risk is...
Zoonotic diseases threaten human health worldwide and are often associated with anthropogenic disturbance. Predicting how disturbance influences spillover risk is critical for effective disease intervention but difficult to achieve at fine spatial scales. Here, we develop a method that learns the spatial distribution of a reservoir species from aerial imagery. Our approach uses neural networks to extract features of known or hypothesized importance from images. The spatial distribution of these features is then summarized and linked to spatially explicit reservoir presence/absence data using boosted regression trees. We demonstrate the utility of our method by applying it to the reservoir of Lassa virus, Mastomys natalensis, within the West African nations of Sierra Leone and Guinea. We show that, when trained using reservoir trapping data and publicly available aerial imagery, our framework learns relationships between environmental features and reservoir occurrence and accurately ranks areas according to the likelihood of reservoir presence.
Topics: Animals; Humans; Lassa Fever; Disease Reservoirs; Zoonoses; Lassa virus; Guinea; Murinae
PubMed: 37737493
DOI: 10.1111/ele.14307 -
International Journal of Biological... Apr 2024The interactions between bovine serum albumin (BSA) and mycophenolic acid (MPA) were investigated in silico through molecular docking and in vitro, using fluorescence...
The interactions between bovine serum albumin (BSA) and mycophenolic acid (MPA) were investigated in silico through molecular docking and in vitro, using fluorescence spectroscopy. Dynamic light scattering and scanning electron microscopy were used to figure out the structure of MPA-Complex (MPA-C). The binding affinity between MPA and BSA was determined, yielding a Kd value of (12.0 ± 0.7) μM, and establishing a distance of 17 Å between the BSA and MPA molecules. The presence of MPA prompted protein aggregation, leading to the formation of MPA-C. The cytotoxicity of MPA-C and its ability to fight Junín virus (JUNV) were tested in A549 and Vero cell lines. It was found that treating infected cells with MPA-C decreased the JUNV yield and was more effective than free MPA in both cell line models for prolonged time treatments. Our results represent the first report of the antiviral activity of this type of BSA-MPA complex against JUNV, as assessed in cell culture model systems. MPA-C shows promise as a candidate for drug formulation against human pathogenic arenaviruses.
Topics: Humans; Serum Albumin, Bovine; Mycophenolic Acid; Molecular Docking Simulation; Virus Replication; Junin virus; Antiviral Agents
PubMed: 38513897
DOI: 10.1016/j.ijbiomac.2024.131023 -
Archives of Virology Oct 2023Lymphocytic choriomeningitis (LCM) is a "neglected" rodent-borne viral zoonotic disease caused by lymphocytic choriomeningitis virus (LCMV) (family Arenaviridae). The...
Lymphocytic choriomeningitis (LCM) is a "neglected" rodent-borne viral zoonotic disease caused by lymphocytic choriomeningitis virus (LCMV) (family Arenaviridae). The aim of this retrospective clinical and laboratory study was to detect LCMV RNA, using RT-PCR, in cerebrospinal fluid samples collected from patients with central nervous system (CNS) infections of unknown aetiology from over a 12-year period in Hungary. Between 2009 and 2020, a total of 74 cerebrospinal fluid samples were tested using an in-house LCMV-specific RT-PCR-based method at the Department of Medical Microbiology and Immunology, University of Pécs. The mean age of the 74 patients included in our study was 24 years (min. 5, max. 74), with a predominance of men (44 [59.5%]; women, 30 [40.5%]). Two (2.7%) cerebrospinal fluid samples were found to be positive for LCMV RNA by RT-PCR and sequencing. The first LCMV case was a 5-year-old preschool boy who had a hamster bite on his left-hand finger, and the second LCMV case was a 74-year-old man who was living in a village and had incipient dementia and a previous permanent functional CNS impairment. The two detected LCMV strains (MW558451 and OM648933) from the year 2020 belonged to two different genetic lineages (I and II). These two cases of CNS inflammation of unknown origin represent the first published human LCMV infections confirmed by molecular methods in Hungary.
Topics: Male; Animals; Cricetinae; Humans; Female; Child, Preschool; Young Adult; Adult; Aged; Lymphocytic Choriomeningitis; Lymphocytic choriomeningitis virus; Hungary; Retrospective Studies; RNA, Viral; Rodentia
PubMed: 37853289
DOI: 10.1007/s00705-023-05905-4 -
Frontiers in Immunology 2023Significant evidence suggests a connection between transplant rejection and the presence of high levels of pre-existing memory T cells. Viral infection can elicit...
INTRODUCTION
Significant evidence suggests a connection between transplant rejection and the presence of high levels of pre-existing memory T cells. Viral infection can elicit viral-specific memory T cells that cross-react with allo-MHC capable of driving allograft rejection in mice. Despite these advances, and despite their critical role in transplant rejection, a systematic study of allo-reactive memory T cells, their specificities, and the role of cross-reactivity with viral antigens has not been performed.
METHODS
Here, we established a model to identify, isolate, and characterize cross-reactive T cells using Nur77 reporter mice (C57BL/6 background), which transiently express GFP exclusively upon TCR engagement. We infected Nur77 mice with lymphocytic choriomeningitis virus (LCMV-Armstrong) to generate a robust memory compartment, where quiescent LCMV-specific memory CD8 T cells could be readily tracked with MHC tetramer staining. Then, we transplanted LCMV immune mice with allogeneic hearts and monitored expression of GFP within MHC-tetramer defined viral-specific T cells as an indicator of their ability to cross-react with alloantigens.
RESULTS
Strikingly, prior LCMV infection significantly increased the kinetics and magnitude of rejection as well as CD8 T cell recruitment into allogeneic, but not syngeneic, transplanted hearts, relative to non-infected controls. Interestingly, as early as day 1 after allogeneic heart transplant an average of ~8% of MHC-tetramer CD8 T cells expressed GFP, in contrast to syngeneic heart transplants, where the frequency of viral-specific CD8 T cells that were GFP was <1%. These data show that a significant percentage of viral-specific memory CD8 T cells expressed T cell receptors that also recognized alloantigens . Notably, the frequency of cross-reactive CD8 T cells differed depending upon the viral epitope. Further, TCR sequences derived from cross-reactive T cells harbored distinctive motifs that may provide insight into cross-reactivity and allo-specificity.
DISCUSSION
In sum, we have established a mouse model to track viral-specific, allo-specific, and cross-reactive T cells; revealing that prior infection elicits substantial numbers of viral-specific T cells that cross-react to alloantigen, respond very early after transplant, and may promote rapid rejection.
Topics: Mice; Animals; CD8-Positive T-Lymphocytes; Mice, Inbred C57BL; Lymphocytic choriomeningitis virus; Virus Diseases; Receptors, Antigen, T-Cell; Isoantigens; Allografts
PubMed: 38143762
DOI: 10.3389/fimmu.2023.1287546