Zoonotic Viruses Research Articles

Molecular Docking of Seaweed-Derived Drug Fucoxanthin Against the Monkeypox Virus.

Background The monkeypox virus (MPXV) is classified as a zoonotic virus of the Poxviridae family, resulting from the MPXV strain of the Orthopoxvirus genus. Seaweeds, or marine macroalgae, are abundant reservoirs of bioactive compounds that demonstrate diverse biological properties, such as antiviral actions. In the field of computational analysis, in silico analysis refers to the use of computer-based methods to study and assess biological systems and processes. To forecast the binding affinity and interaction between the discovered chemical and the target proteins of the MPXV, a molecular docking analysis was conducted. Aim The research aims to conduct an in silico examination of a protein-ligand interaction of a drug produced from seaweed that targets the MPXV. Methodology Protein Data Bank (PDB) and PubChem databases provided MPXV methyltransferase and fucoxanthin ligand compounds. AutoDockTools 1.5.7 calculated the molecular docking using the Lamarckian genetic algorithm. Autogrid created a grid box around target 8B07 active site hotspot residues. Each docked molecule's docking parameters were obtained from 100 docking experiments with a maximum of 2.5 × 106 energy evaluations, a 0.02 mutation rate, and a 0.8 crossover rate. The population comprised 250 randomly selected volunteers. PyMOL was utilized to observe ligand fragment interactions. Results The binding energy of the ligand fucoxanthin was -5.46 kcal/mol. Fucoxanthin interacts with receptor molecules via hydrogen bonding at the amino acid level: Chain A: PHE188 and TYR189; and Chain B: LYS33, GLN37, GLY38, GLY96, ARG97, PHE115, PRO202, and SER203. The higher the negative docking score, the stronger the binding affinity between the receptor and ligand molecules, indicating that bioactive substances are more effective. Conclusion The findings of this study indicate that fucoxanthin, a pharmaceutical derivative generated from seaweed, had antiviral activity against the MPXV. This conclusion was reached based on protein-ligand interactions.

Selective deforestation and exposure of African wildlife to bat-borne viruses

Proposed mechanisms of zoonotic virus spillover often posit that wildlife transmission and amplification precede human outbreaks. Between 2006 and 2012, the palm Raphia farinifera, a rich source of dietary minerals for wildlife, was nearly extirpated from Budongo Forest, Uganda. Since then, chimpanzees, black-and-white colobus, and red duiker were observed feeding on bat guano, a behavior not previously observed. Here we show that guano consumption may be a response to dietary mineral scarcity and may expose wildlife to bat-borne viruses. Videos from 2017–2019 recorded 839 instances of guano consumption by the aforementioned species. Nutritional analysis of the guano revealed high concentrations of sodium, potassium, magnesium and phosphorus. Metagenomic analyses of the guano identified 27 eukaryotic viruses, including a novel betacoronavirus. Our findings illustrate how “upstream” drivers such as socioeconomics and resource extraction can initiate elaborate chains of causation, ultimately increasing virus spillover risk.

Prediction of viral spillover risk based on the mass action principle

Infectious zoonotic disease emergence, through spillover events, is of global concern and has the potential to cause significant harm to society, as recently demonstrated by COVID-19. More than 70% of the 400 infectious diseases that emerged in the past five decades have a zoonotic origin, including all recent pandemics. There have been several approaches used to predict the risk of spillover through some of the known or suspected infectious disease emergence drivers, largely using correlative approaches. Here, we predict the spatial distribution of spillover risk by approximating general transmission through animal and human interactions. These mass action interactions are approximated through the multiplication of the spatial distribution of zoonotic virus diversity and human population density. Although our results indicate higher risk in regions along the equator and in Southeast Asia where both virus diversity and human population density are high, it should be noted that this is primarily a conceptual exercise. We compared our spillover risk map to key factors, including the model inputs of zoonotic virus diversity estimate map, human population density map, and the spatial distribution of species richness. Despite the limitations of this approach, this viral spillover map is a step towards developing a more comprehensive spillover risk prediction system to inform global monitoring.

Curcumin as a natural potential drug candidate against important zoonotic viruses and prions: A narrative review.

Zoonotic diseases are major public health concerns and undeniable threats to human health. Among Zoonotic diseases, zoonotic viruses and prions are much more difficult to eradicate, as they result in higher infections and mortality rates. Several investigations have shown curcumin, the active ingredient of turmeric, to have wide spectrum properties such as anti-microbial, anti-vascular, anti-inflammatory, anti-tumor, anti-neoplastic, anti-oxidant, and immune system modulator properties. In the present study, we performed a comprehensive review of existing in silico, in vitro, and in vivo evidence on the antiviral (54 important zoonotic viruses) and anti-prion properties of curcumin and curcuminoids in PubMed, Google Scholar, Science Direct, Scopus, and Web of Science databases. Database searches yielded 13,380 results, out of which 216 studies were eligible according to inclusion criteria. Of 216 studies, 135 (62.5%), 24 (11.1%), and 19 (8.8%) were conducted on the effect of curcumin and curcuminoids against SARS-CoV-2, Influenza A virus, and dengue virus, respectively. This review suggests curcumin and curcuminoids as promising therapeutic agents against a wide range of viral zoonoses by targeting different proteins and signaling pathways.

Global distribution, cross-species transmission, and receptor binding of canine parvovirus-2: Risks and implications for humans

For canine parvovirus -2 (CPV-2), a zoonotic virus capable of cross-species transmission in animals, the amino acid changes of capsid protein VP2 are key factors when binding to other species' transferrin receptors (TfR). CPV-2 variants can spread from felines and canines, for example, to Carnivora, Artiodactyla, and Pholidota species, and CPV-2c variants are essential to spread from Carnivora to Artiodactyla and Pholidota species in particular. In our study, a CPV-2a variant maintained a relatively stable trend, and the proportion of CPV-2c gradually rose from 1980 to 2021. The VP2 amino acid sequence analysis showed that five amino acid mutations at 426E/D, 305H/D, and 297S may be necessary for the virus to bind to different host receptors. Meanwhile, receptor-binding loop regions and amino acid sites 87 L, 93 N, 232I, and 305Y were associated with CPV-2 cross-species transmission. The homology of TfRs in different hosts infected with CPV-2 ranged from 77.2 % to 99.0 %, and from pig to feline, canine, and humans was 80.7 %, 80.4 %, and 77.2 %, respectively. The amino acid residues of TfRs involved in the viral binding in those hosts are highly conserved, which suggests that CPV-2 may be capable of pig-to-human transmission. Our analysis of the origin, evolutionary trend, cross-species transmission dynamics, and genetic characteristics of CPV-2 when binding to host receptors provides a theoretical basis for further research on CPV-2's mechanism of cross-species transmission and for establishing an early warning and monitoring mechanism for the possible threat of CPV-2 to animal–human public security.

Interaction of Nipah Virus F and G with the Cellular Protein Cortactin Discovered by a Proximity Interactome Assay.

Nipah virus (NiV) is a highly lethal zoonotic virus with a potential large-scale outbreak, which poses a great threat to world health and security. In order to explore more potential factors associated with NiV, a proximity labeling method was applied to investigate the F, G, and host protein interactions systematically. We screened 1996 and 1524 high-confidence host proteins that interacted with the NiV fusion (F) glycoprotein and attachment (G) glycoprotein in HEK293T cells by proximity labeling technology, and 863 of them interacted with both F and G. The results of GO and KEGG enrichment analysis showed that most of these host proteins were involved in cellular processes, molecular binding, endocytosis, tight junction, and other functions. Cytoscape software (v3.9.1) was used for visual analysis, and the results showed that Cortactin (CTTN), Serpine mRNA binding protein 1 (SERBP1), and stathmin 1 (STMN1) were the top 20 proteins and interacted with F and G, and were selected for further validation. We observed colocalization of F-CTTN, F-SERBP1, F-STMN1, G-CTTN, G-SERBP1, and G-STMN1 using confocal fluorescence microscopy, and the results showed that CTTN, SERBP1, and STMN1 overlapped with NiV F and NiV G in HEK293T cells. Further studies found that CTTN can significantly inhibit the infection of the Nipah pseudovirus (NiVpv) into host cells, while SERBP1 and STMN1 had no significant effect on pseudovirus infection. In addition, CTTN can also inhibit the infection of the Hendra pseudovirus (HeVpv) in 293T cells. In summary, this study revealed that the potential host proteins interacted with NiV F and G and demonstrated that CTTN could inhibit NiVpv and HeVpv infection, providing new evidence and targets for the study of drugs against these diseases.

Immunopathology of emerging and re-emerging viral infections: an updated overview

Humankind has witnessed increased frequency of emerging and re-emerging viral diseases in the past few decades. The major categories of pathogenic emerging and re-emerging viral infections include respiratory, arthropod-borne and bat-borne zoonotic viruses. These viral infections are notorious for causing immune dysregulation and have the potential to mount excessive immune reaction, causing immunopathology that includes tissue injury, systemic inflammation, multi-organ failure and even death. A better understanding of the emerging or re-emerging viral-mediated immunomodulation is necessary for controlling the virus, while preventing severity of the disease associated with exaggerated immune response. In this article, we review the current understanding of emerging and re-emerging respiratory, arboviral and bat-borne zoonotic viruses; and consequent immune dysregulation or immunopathology associated with these viral infections.

A novel approach to designing viral precision vaccines applied to SARS-CoV-2.

Efficient precision vaccines against several highly pathogenic zoonotic viruses are currently lacking. Proteolytic activation is instrumental for a number of these viruses to gain host-cell entry and develop infectivity. For SARS-CoV-2, this process is enhanced by the insertion of a furin cleavage site at the junction of the spike protein S1/S2 subunits upstream of the metalloprotease TMPRSS2 common proteolytic site. Here, we describe a new approach based on specific epitopes selection from the region involved in proteolytic activation and infectivity for the engineering of precision candidate vaccinating antigens. This approach was developed through its application to the design of SARS-CoV-2 cross-variant candidates vaccinating antigens. It includes an in silico structural analysis of the viral region involved in infectivity, the identification of conserved immunogenic epitopes and the selection of those eliciting specific immune responses in infected people. The following step consists of engineering vaccinating antigens that carry the selected epitopes and mimic their 3D native structure. Using this approach, we demonstrated through a Covid-19 patient-centered study of a 500 patients' cohort, that the epitopes selected from SARS-CoV-2 protein S1/S2 junction elicited a neutralizing antibody response significantly associated with mild and asymptomatic COVID-19 (p<0.001), which strongly suggests protective immunity. Engineered antigens containing the SARS-CoV-2 selected epitopes and mimicking the native epitopes 3D structure generated neutralizing antibody response in mice. Our data show the potential of this combined computational and experimental approach for designing precision vaccines against viruses whose pathogenicity is contingent upon proteolytic activation.

A case series of patients with ophthalmic manifestations of monkeypox in Spain

Monkeypox virus (MPXV) is a zoonotic orthopox DNA virus presently causing a global outbreak. The mucosae are affected in 41% of the cases; the nasal and eye regions are the least affected (1%). The most frequent eye infection is conjunctivitis with severe cases of corneal affection leading to permanent visual sequelae. We describe two cases of patients presenting facial edema, erythema, and vesiculo-pustular lesions with confirmed positive MPXV DNA polymerase chain reaction (PCR). Preseptal cellulitis and MPXV infection were diagnosed and treated with antibiotics and tecovirimat. A third patient was admitted to the hospital with pain and redness of the right eye and vesiculo-pustular skin lesions. On ophthalmological examination, he was diagnosed with a corneal ulcer and a creamy white infiltrate and was treated with systemic tecovirimat and ciprofloxacin eye drops. Healthcare professionals should be familiar with ocular manifestations of MPXV infection and consult ophthalmologists to reduce the risk of potentially vision-threatening complications.

Assessing environmental exposure to viruses in wastewater treatment plant and swine farm scenarios with next-generation sequencing and occupational risk approaches

Occupational exposure to pathogens can pose health risks. This study investigates the viral exposure of workers in a wastewater treatment plant (WWTP) and a swine farm by analyzing aerosol and surfaces samples. Viral contamination was evaluated using quantitative polymerase chain reaction (qPCR) assays, and target enrichment sequencing (TES) was performed to identify the vertebrate viruses to which workers might be exposed. Additionally, Quantitative Microbial Risk Assessment (QMRA) was conducted to estimate the occupational risk associated with viral exposure for WWTP workers, choosing Human Adenovirus (HAdV) as the reference pathogen. In the swine farm, QMRA was performed as an extrapolation, considering a hypothetical zoonotic virus with characteristics similar to Porcine Adenovirus (PAdV). The modelled exposure routes included aerosol inhalation and oral ingestion through contaminated surfaces and hand-to-mouth contact.HAdV and PAdV were widespread viruses in the WWTP and the swine farm, respectively, by qPCR assays. TES identified human and other vertebrate viruses WWTP samples, including viruses from families such as Adenoviridae, Circoviridae, Orthoherpesviridae, Papillomaviridae, and Parvoviridae. In the swine farm, most of the identified vertebrate viruses were porcine viruses belonging to Adenoviridae, Astroviridae, Circoviridae, Herpesviridae, Papillomaviridae, Parvoviridae, Picornaviridae, and Retroviridae.QMRA analysis revealed noteworthy risks of viral infections for WWTP workers if safety measures are not taken. The probability of illness due to HAdV inhalation was higher in summer compared to winter, while the greatest risk from oral ingestion was observed in workspaces during winter. Swine farm QMRA simulation suggested a potential occupational risk in the case of exposure to a hypothetical zoonotic virus.This study provides valuable insights into WWTP and swine farm worker's occupational exposure to human and other vertebrate viruses. QMRA and NGS analyses conducted in this study will assist managers in making evidence-based decisions, facilitating the implementation of protection measures, and risk mitigation practices for workers.

In silico identification of novel pre-microRNA genes in Rift valley fever virus suggest new pathomechanisms for embryo-fetal dysgenesis

ABSTRACT 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.

Species-specific responses during Seoul orthohantavirus infection in human and rat lung microvascular endothelial cells.

Seoul orthohantavirus (SEOV) is a rat-borne zoonotic virus that is transmitted via inhalation of aerosolized infectious excreta, and can cause hemorrhagic fever with renal syndrome (HFRS) in humans worldwide. In rats, SEOV predominantly exists as a persistent infection in the absence of overt clinical signs. Lack of disease in rats is attributed to downregulation of pro-inflammatory and upregulation of regulatory host responses. As lung microvascular endothelial cells (LMECs) represent a primary target of infection in both human and rats, infections in these cells provide a unique opportunity to study the central role of LMECs in the dichotomy between pathogenicity in both species. In this study, host responses to SEOV infection in primary human and rat LMECs were directly compared on a transcriptional level. As infection of rat LMECs was more efficient than human LMECs, the majority of anti-viral defense responses were observed earlier in rat LMECs. Most prominently, SEOV-induced processes in both species included responses to cytokine stimulus, negative regulation of innate immune responses, responses to type I and II interferons, regulation of pattern recognition receptor signaling and MHC-I signaling. However, over time, in the rat LMECs, responses shifted from an anti-viral state towards a more immunotolerant state displayed by a PD-L1, B2M-, JAK2-focused interaction network aiding in negative regulation of cytotoxic CD8-positive T cell activation. This suggests a novel mechanism by which species-specific orthohantavirus-induced endothelium and T cell crosstalk may play a crucial role in the development of acute disease in humans and persistence in rodents.

Unveiling the Hidden Regulators: The Impact of lncRNAs on Zoonoses.

Zoonoses are diseases and infections naturally transmitted between humans and vertebrate animals. They form the dominant group of diseases among emerging infectious diseases and represent critical threats to global health security. This dilemma is largely attributed to our insufficient knowledge of the pathogenesis regarding zoonotic spillover. Long non-coding RNAs (lncRNAs) are transcripts with limited coding capacity. Recent technological advancements have enabled the identification of numerous lncRNAs in humans, animals, and even pathogens. An increasing body of literature suggests that lncRNAs function as key regulators in zoonotic infection. They regulate immune-related epigenetic, transcriptional, and post-transcriptional events across a broad range of organisms. In this review, we discuss the recent research progress on the roles of lncRNAs in zoonoses. We address the classification and regulatory mechanisms of lncRNAs in the interaction between host and zoonotic pathogens. Additionally, we explore the surprising function of pathogen-derived lncRNAs in mediating the pathogenicity and life cycle of zoonotic bacteria, viruses, and parasites. Understanding how these lncRNAs influence the zoonotic pathogenesis will provide important therapeutic insights to the prevention and control of zoonoses.

To the 55th аnniversary of the Department of Virus Ecology with the Scientific and Practical Center for the Ecology and Epidemiology of Influenza (D.I. Ivanovsky Institute of Virology of the N.F. Gamaleya National Research Center for Epidemiology and Microbiology of the Ministry of Health of Russian Federation)

The article presents historical aspects and key achievements of the Department of Virus Ecology (DVE) with the Scientific and Practical Center for Influenza Ecology and Epidemiology, which was established in 1969 at the D.I. Ivanovsky Institute of Virology of Academy of Medical Sciences of the USSR. For over 50 years, the DVE has been devoted to addressing fundamental issues in virus ecology, including the formation of viral populations in nature, and conducting comprehensive large-scale studies in the interest of the state’s biosecurity. The department’s primary focus is on particularly dangerous (arboviral) and socially significant (influenza and other acute respiratory viral infections, parenteral hepatitis) viral infections. As a result of this extensive work in the Northern Eurasia region, over 2,000 strains of zoonotic viruses (17 genera, 8 families), ecologically linked to various arthropod vectors and vertebrate hosts, have been isolated. Many of them have been registered in international catalogs as new species. The role of these isolated viruses in human pathology has been studied, new viral infections have been described, and diagnostic preparations have been developed. The scientific results obtained by the department are of high priority and internationally recognized.

Unveiling the impacts of land use on the phylogeography of zoonotic New World Hantaviruses

Billions of genomic sequences and records of species occurrence are available in public repositories (e.g. National Center for Biotechnology Information, NCBI and the Global Biodiversity Information Facility, GBIF). By implementing analytical tools from different scientific disciplines, data mining these databases can aid in the global surveillance of zoonotic pathogens that circulate among wildlife. We illustrate this by investigating the Hantavirus–rodent system in the Americas, i.e. New World Hantaviruses (NWH). First, we considered the circulation of pathogenic NWH among Cricetidae rodents, by inferring the phylogenetic links among 277 genomic samples of the S segment (N protein) of NWH found in 55 species. Second, we used machine learning to assess the impact of land use on the probability of presence of the rodent species linked with reservoirs of pathogenic Hantaviruses. Our results show that hosts are widely present across the Americas. Some hosts are present in the primary forest and agricultural land, but not in the secondary forest, whereas other hosts are present in secondary forest and agricultural land. The diversity of host species allows Hantavirus to circulate in a wide spectrum of habitats, in particular rural rather than urban. We highlight that public repositories of genomic data and species occurrence are very useful resources for monitoring potential enzootic transmission and spillover of zoonotic viruses in relation with the changes that humans produce in the biosphere.

Protection of Chickens against H9N2 Avian Influenza Isolates with a Live Vector Vaccine Expressing Influenza Hemagglutinin Gene Derived from Y280 Avian Influenza Virus.

Since the outbreak of the H9N2/Y439 avian influenza virus in 1996, the Korean poultry industry has incurred severe economic losses. A novel possibly zoonotic H9N2 virus from the Y280-like lineage (H9N2/Y280) has been prevalent in Korea since June 2020, posing a threat to the poultry sector. Rapid mutation of influenza viruses urges the development of effective vaccines against newly generated strains. Thus, we engineered a recombinant virus rHVT/Y280 to combat H9N2/Y280. We integrated the hemagglutinin (HA) gene of the H9N2/Y280 strain into the US2 region of the herpesvirus of turkeys (HVT) Fc126 vaccine strain, utilizing CRISPR/Cas9 gene-editing technology. The successful construction of rHVT/Y280 was confirmed by polymerase chain reaction and sequencing, followed by efficacy evaluation. Four-day-old specific pathogen-free chickens received the rHVT/Y280 vaccine and were challenged with the H9N2/Y280 strain A21-MRA-003 at 3 weeks post-vaccination. In 5 days, there were no gross lesions among the vaccinated chickens. The rHVT/Y280 vaccine induced strong humoral immunity and markedly reduced virus shedding, achieving 100% inhibition of virus recovery in the cecal tonsil and significantly lowering tissue viral load. Thus, HVT vector vaccines expressing HA can be used for protecting poultry against H9N2/Y280. The induction of humoral immunity by live vaccines is vital in such cases. In summary, the recombinant virus rHVT/Y280 is a promising vaccine candidate for the protection of chickens against the H9N2/Y280.

Factors Involved in the Immunological Protection against Rabies Virus in Dogs in Spain.

Rabies, a viral disease spread by infected animal bites that causes encephalitis in humans and other mammals, is a neglected infectious disease present on all continents except Antarctica. Spain has been free of terrestrial rabies since 1978. However, due to its geographical situation, it represents a bridge for imported cases from an endemic continent such as Africa to Europe. Rabies vaccination in dogs is an essential preventive tool against this zoonosis. The aim of this study was to determine the state of the immune response against rabies virus in dogs in Spain and to demonstrate whether several factors that have been previously related to the influence of the seroprevalence of this species are involved here. The seroconversion level of this zoonotic virus was assessed in a total of 1060 animals. Indirect ELISA was used to obtain data for statistical analysis to evaluate the studied variables. Working under the concept of One Health, this study provides relevant information to be taken into consideration not only to prevent re-emergence in countries free of this disease but also for prevention and control in endemic countries.

Nipah Virus Disease: An Updated Review

The Nipah virus (NiV) is a member of the Paramyxoviridae family of zoonotic viruses that is extremely contagious and potentially fatal. The Nipah virus was first discovered in 1999 during an outbreak in Malaysia. Since then, it has periodically caused outbreaks throughout South and Southeast Asia, especially in Bangladesh and India, and it continues to be a serious public health concern. The virus is primarily transmitted to humans through direct contact with infected fruit bats, which serve as natural reservoir hosts for the Nipah virus. Human-to-human transmission can also happen when infected people's body fluids come into close contact with one another. The Nipah virus has a high death rate that varies depending on the outbreak and can cause a variety of clinical presentations, including encephalitis, severe respiratory illnesses, and asymptomatic infections. Fever, headache, dizziness, drowsiness, and confusion are common signs of Nipah virus infections, which may lead to the rapid onset of coma in the patient. The Nipah virus does not presently have a specific antiviral treatment; instead, infection control methods and supportive care are the foundation of management to stop the virus from spreading. Nipah virus outbreaks must be stopped with an approach that includes community involvement, public health education, and surveillance of both human and animal populations. Additionally, efforts are directed toward developing vaccines as a more potent form of prevention. The Nipah virus is a clear reminder of the continuous threat that newly emerging infectious diseases pose, as well as the necessity of having strong surveillance systems and quick response times in place to lessen the effects that these outbreaks have on public health.

The Multi-Kingdom Microbiome of Wintering Migratory Birds in Poyang Lake, China.

Wild birds are a natural reservoir for zoonotic viruses. To clarify the role of migratory birds in viruses spread in Poyang Lake, we investigated the microbiome of 250 wild bird samples from 19 species in seven orders. The bacterial and viral content abundance and diversity were preliminarily evaluated by Kraken2 and Bracken. After de novo assembly by Megahit and Vamb, viral contigs were identified by CheckV. The reads remapped to viral contigs were quantified using Bowtie2. The bacterial microbiome composition of the samples covers 1526 genera belonging to 175 bacterial orders, while the composition of viruses covers 214 species belonging to 22 viral families. Several taxonomic biomarkers associated with avian carnivory, oral sampling, and raptor migration were identified. Additionally, 17 complete viral genomes belonging to Astroviridae, Caliciviridae, Dicistroviridae, Picornaviridae, and Tombusviridae were characterized, and their phylogenetic relationships were analyzed. This pioneering metagenomic study of migratory birds in Poyang Lake, China illuminates the diverse microbial landscape within these birds. It identifies potential pathogens, and uncovers taxonomic biomarkers relevant to varied bird habitats, feeding habits, ecological classifications, and sample types, underscoring the public health risks associated with wintering migratory birds.

MHC-I alleles mediate clearance and antibody response to the zoonotic Lassa virus in Mastomys rodent reservoirs.

West African Mastomys rodents are the primary reservoir of the zoonotic Lassa virus (LASV). The virus causes haemorrhagic Lassa fever and considerable mortality in humans. To date, the role of Mastomys immunogenetics in resistance to, and persistence of, LASV infections is largely unknown. Here, we investigated the role of Major Histocompatibility Complex class I (MHC-I) on LASV infection status (i.e., active vs. cleared infection, determined via PCR and an immunofluorescence assay on IgG antibodies, respectively) in Mastomys natalensis and M. erythroleucus sampled within southwestern Nigeria. We identified more than 190 and 90 MHC-I alleles by Illumina high throughput-sequencing in M. natalensis and M. erythroleucus, respectively, with different MHC allele compositions and frequencies between LASV endemic and non-endemic sites. In M. natalensis, the MHC allele ManaMHC-I*006 was negatively associated with active infections (PCR-positive) and positively associated with cleared infections (IgG-positive) simultaneously, suggesting efficient immune responses that facilitate LASV clearance in animals carrying this allele. Contrarily, alleles ManaMHC-I*008 and ManaMHC-I*021 in M. natalensis, and MaerMHC-I*008 in M. erythroleucus, were positively associated with active infection, implying susceptibility. Alleles associated with susceptibility shared a glutamic acid at the positively selected codon 57, while ManaMHC-I*006 featured an arginine. There was no link between number of MHC alleles per Mastomys individual and LASV prevalence. Thus, specific alleles, but not MHC diversity per se, seem to mediate antibody responses to viremia. We conclude that co-evolution with LASV likely shaped the MHC-I diversity of the main LASV reservoirs in southwestern Nigeria, and that information on reservoir immunogenetics may hold insights into transmission dynamics and zoonotic spillover risks.