A systematic review on current approaches in bat virus discovered between 2018 and 2022.

Zoonotic viruses are widely seen as the primary threat for future pandemics. Bats are the most diverse group of mammals, with more than 1400 species distributed across most habitats on Earth. So far, 31 known virus families were associated with bats, although the understanding of most viruses were insufficient. Continuous efforts to discover, understand and monitor these bats viruses, is thereby an area of public health interest. This systematic review was designed to catalogue publications reporting novel bat virus discoveries within PubMed, SCOPUS, and Web of Science databases, within a 5-year period from 2018 to 2022. Various experimental parameters, including sampling locations, methodology, bat species diversity, similarity to known viruses, species demarcation of new viruses, and genomic sequencing strategies, were extracted from 41 publications and analyzed. In total, 72 novel viruses from 19 virus families were identified between 2018 and 2022, particularly from Genomoviridae (DNA viruses) and Coronaviridae (RNA viruses). That said, only a limited number of bat families featured extensively despite noticeable shift towards next generation sequencing methods and metagenomics pipeline for virus identification across different sampling methods. This review aims to provide a comprehensive analysis of the global efforts made over the past five years to identify and characterize emerging viruses in bat species, and to provide a detailed overview of the current technologies and methodologies used in these studies.

Biological Characteristics and Pathogenesis of Monkeypox Virus: An Overview.

Although the smallpox virus has been eradicated worldwide, the World Health Organization (WHO) has issued a warning about the virus's potential to propagate globally. The WHO labeled monkeypox a world public health emergency in July 2022, requiring urgent prevention and treatment. The monkeypox virus is a part of the Poxviridae family, Orthopoxvirus genus, and is accountable for smallpox, which has killed over a million people in the past. Natural hosts of the virus include squirrels, Gambian rodents, chimpanzees, and other monkeys. The monkeypox virus has transmitted to humans through primary vectors (various animal species) and secondary vectors, including direct touch with lesions, breathing particles from body fluids, and infected bedding. The viral particles are ovoid or brick-shaped, 200-250 nm in diameter, contain a single double-stranded DNA molecule, and reproduce only in the cytoplasm of infected cells. Monkeypox causes fever, cold, muscle pains, headache, fatigue, and backache. The phylogenetic investigation distinguished between two genetic clades of monkeypox: the more pathogenic Congo Basin clade and the West Africa clade. In recent years, the geographical spread of the human monkeypox virus has accelerated despite a paucity of information regarding the disease's emergence, ecology, and epidemiology. Using lesion samples and polymerase chain reaction (PCR), the monkeypox virus was diagnosed. In the USA, the improved Ankara vaccine can now be used to protect people who are at a higher risk of getting monkeypox. Antivirals that we have now work well against smallpox and may stop the spread of monkeypox, but there is no particular therapy for monkeypox.

Drivers for a pandemic due to avian influenza and options for One Health mitigation measures.

Avian influenza viruses (AIV) remain prevalent among wild bird populations in the European Union and European Economic Area (EU/EEA), leading to significant illness in and death of birds. Transmission between bird and mammal species has been observed, particularly in fur animal farms, where outbreaks have been reported. While transmission from infected birds to humans is rare, there have been instances of exposure to these viruses since 2020 without any symptomatic infections reported in the EU/EEA. However, these viruses continue to evolve globally, and with the migration of wild birds, new strains carrying potential mutations for mammalian adaptation could be selected. If avian A(H5N1) influenza viruses acquire the ability to spread efficiently among humans, large-scale transmission could occur due to the lack of immune defences against H5 viruses in humans. The emergence of AIV capable of infecting mammals, including humans, can be facilitated by various drivers. Some intrinsic drivers are related to virus characteristics or host susceptibility. Other drivers are extrinsic and may increase exposure of mammals and humans to AIV thereby stimulating mutation and adaptation to mammals. Extrinsic drivers include the ecology of host species, such as including wildlife, human activities like farming practices and the use of natural resources, climatic and environmental factors. One Health measures to mitigate the risk of AIV adapting to mammals and humans focus on limiting exposure and preventing spread. Key options for actions include enhancing surveillance targeting humans and animals, ensuring access to rapid diagnostics, promoting collaboration between animal and human sectors, and implementing preventive measures such as vaccination. Effective communication to different involved target audiences should be emphasised, as well as strengthening veterinary infrastructure, enforcing biosecurity measures at farms, and reducing wildlife contact with domestic animals. Careful planning of poultry and fur animal farming, especially in areas with high waterfowl density, is highlighted for effective risk reduction.

Human cytokeratin 1 plays a role in the interaction of Pteropine orthoreovirus with Hek293 cells but not HeLa cells.

Pteropine orthoreovirus (PRV) causes respiratory tract infections in humans. Despite its emergence as a zoonotic and respiratory virus, little is known about its cell tropism, which hampers progress in fully understanding its pathogenesis in humans. Hek293 cells are most susceptible to PRV infection, while HeLa cells are the least. Human cytokeratin 1 (CK1) was identified as the protein that interacts with PRV. The immunofluorescence assay and qPCR results revealed prior treatment with anti-CK1 may provide Hek293 cells protection against PRV. The KRT1-knockout Hek293 cells were less susceptible to PRV infection. Further study into the pathogenesis of PRV in humans is needed.

Severe zoonotic viruses carried by different species of bats and their regional distribution.

BACKGROUND: Bats have garnered increased attention in the field of life sciences for their typical biological characteristics of carrying a variety of zoonotic viruses without disease, long lifespans, low tumorigenesis rates, and high metabolism. When it was found that bats can carry the rabies virus, over 60 years of research revealed that bats host over 4100 distinct viruses, including Ebola virus and SARS-CoV. OBJECTIVES: This paper primarily reviews the profiles of zoonotic viruses carried by bats across various regions globally. The review aims to provide a foundation and reference for future research on monitoring zoonotic viruses in diverse global regions and bat species, exploring the coevolutionary relationship between bats and viruses, understanding the tolerance mechanisms of bat B cells, prevention, and treatment of zoonotic diseases caused by bats. SOURCES: The search used 'bat', 'bats', 'rabies virus', 'Dengue virus', 'West Nile virus', 'Zika virus', 'St. Louis encephalitis virus', 'Japanese encephalitis virus', 'Hantavirus', 'Novel hantavirus', 'Rift Valley fever virus', 'Crimean Congo hemorrhagic fever virus', 'Paramyxovirus', 'Nipah virus', 'Hendra virus', 'Menangle virus', 'Tioman virus', 'Marburg Virus', 'Bombali virus', 'Ebola virus', 'Influenza A virus', 'coronavirus', 'Hepatitis B virus', and 'Hepatitis E virus' as text in PubMed. CONTENT: A total of 147 references were obtained. Surveys on severe zoonotic virus carriage have been limited to only 83 bat species belonging to nine families, which are distributed all over the world. We also briefly describe the antibody responses and B-cell molecules in bats. IMPLICATIONS: Several viruses have been found in different species of bats. This suggests that bats may be important hosts for future viral infectious diseases. Particularly in recent years, the close correlation between human infection pandemics caused by coronaviruses and bats highlights the pressing need to comprehend the species, tolerance, and coevolutionary mechanisms of zoonotic viruses carried by different bat species.

Sequence-Based Antigenic Analyses of H1 Swine Influenza A Viruses from Colombia (2008-2021) Reveals Temporal and Geographical Antigenic Variations.

Swine influenza is a respiratory disease that affects the pork industry and is a public health threat. It is caused by type A influenza virus (FLUAV), which continuously undergoes genetic and antigenic variations. A large amount of information regarding FLUAV in pigs is available worldwide, but it is limited in Latin America. The HA sequences of H1 subtype FLUAV-positive samples obtained from pigs in Colombia between 2008-2021 were analyzed using sequence-based antigenic cartography and N-Glycosylation analyses. Of the 12 predicted global antigenic groups, Colombia contained five: four corresponding to pandemic strains and one to the classical swine H1N1 clade. Circulation of these clusters was observed in some regions during specific years. Ca2 was the immunodominant epitope among Colombian viruses. The counts of N-Glycosylation motifs were associated with the antigenic cluster ranging from three to five. The results show for the first time the existence of antigenic diversity of FLUAV in Colombia and highlight the impact of spatial and temporal factors on this diversity. This study provides information about FLUAV variability in pigs under natural conditions in the absence of vaccination and emphasizes the need for surveillance of its phylogenetic and antigenic characteristics.

Tanapox, South Africa, 2022.

Tanapox is a rarely diagnosed zoonosis known to be endemic to equatorial Africa. All previously reported human cases were acquired within 10° north or south of the Equator, most recently 19 years ago. We describe a human case of tanapox in South Africa (24° south of the Equator). Expanded surveillance for this pathogen is warranted.

Characterization of experimental Shuni virus infection in the mouse.

Shuni virus (SHUV), an orthobunyavirus of the Simbu serogroup, was initially isolated in Nigeria in the 1960s, further detected in other African countries and in the Middle East, and is now endemic in Israel. Transmitted by blood-sucking insects, SHUV infection is associated with neurological disease in cattle and horses, and with abortion, stillbirth, or the birth of malformed offspring in ruminants. Surveillance studies also indicated a zoonotic potential. This study aimed to test the susceptibility of the well-characterized interferon (IFN)-α/ß receptor knock-out mouse model (Ifnar-/-), to identify target cells, and to describe the neuropathological features. Ifnar-/-mice were subcutaneously infected with two different SHUV strains, including a strain isolated from the brain of a heifer showing neurological signs. The second strain represented a natural deletion mutant exhibiting a loss of function of the S-segment-encoded nonstructural protein NSs, which counteracts the host's IFN response. Here it is shown that Ifnar-/-mice are susceptible to both SHUV strains and can develop fatal disease. Histological examination confirmed meningoencephalomyelitis in mice as described in cattle with natural and experimental infections. RNA in situ hybridization was applied using RNA Scope™ for SHUV detection. Target cells identified included neurons and astrocytes, as well as macrophages in the spleen and gut-associated lymphoid tissue. Thus, this mouse model is particularly beneficial for the evaluation of virulence determinants in the pathogenesis of SHUV infection in animals.

Surveillance, isolation and genomic characterization of Pteropine orthoreovirus of probable bat origin among patients with acute respiratory infection in Malaysia.

Pteropine orthoreovirus (PRV), an emerging bat-borne virus, has been linked to cases of acute respiratory infections (ARI) in humans. The prevalence, epidemiology and genomic diversity of PRV among ARI of unknown origin were studied. Among 632 urban outpatients tested negative for all known respiratory viruses, 2.2% were PRV-positive. Patients mainly presented with moderate to severe forms of cough, sore throat and muscle ache, but rarely with fever. Phylogenetic analysis revealed that over 90% of patients infected with the Melaka virus (MelV)-like PRV, while one patient infected with the Pulau virus previously found only in fruit bats. Human oral keratinocytes and nasopharyngeal epithelial cells were susceptible to clinical isolates of PRV, including the newly isolated MelV-like 12MYKLU1034. Whole genome sequence of 12MYKLU1034 using Nanopore technique revealed a novel reassortant strain. Evolutionary analysis of the global PRV strains suggests the continuous evolution of PRV through genetic reassortment among PRV strains circulating in human, bats and non-human primate hosts, creating a spectrum of reassortant lineages with complex evolutionary characteristics. In summary, the role of PRV as a common etiologic agent of ARI is evident. Continuous monitoring of PRV prevalence, pathogenicity and diversity among human and animal hosts is important to trace the emergence of novel reassortants.

Monkeypox and oral lesions associated with its occurrence: a systematic review and meta-analysis.

Background: A zoonotic, double-stranded DNA virus belonging to the genus Orthopoxvirus, the mpox virus (MPXV) is most common in tropical regions of Central and West Africa. The frequency of monkeypox (mpox) cases, however, has sharply climbed globally since May 2022. Objectives: To establish the threat of mpox in terms of the oral lesions caused in sufferers. Materials and methods: After a thorough study of the literature identified in the PubMed, Web of Science, and Cochrane library databases using the PRISMA framework, 103 papers were found. Using inclusion and exclusion criteria, we chose research that was relevant for our review before shortlisting 14 papers that conformed to the review's guidelines. Results: In the 14 selected studies, it was found that oral lesions were among the first clinical signs of a mpox affliction, with ulcers on the dorsal surface of tongue lips being the most common areas affected. Conclusion: The rarely observed oral lesions of mpox infection may help in the diagnosis and management of this condition. It is critical to keep in mind that recognising and detecting oral lesions in mpox patients opens the door to more research and efficient patient management.

All That We Need to Know About the Current and Past Outbreaks of Monkeypox: A Narrative Review.

Monkeypox is a rare, zoonotic viral illness that was initially endemic mainly to Africa. The virus later spread to non-African countries and, in 2022, it exploded on a global scale, with an unprecedented number of cases. The rapid, multi-country transmission, primarily in men who have sex with men (MSM), and evolving clinical manifestations and demographic traits of the current outbreak have raised serious concerns among the international health community. An in-depth inquiry into the past and present outbreaks are required, especially when contrasting features are witnessed across countries and outbreaks. This narrative review aims to summarize the evolution in the epidemiology, clinical features, mode of transmission, and management protocol of human monkeypox infection (H-MPVX) over the decades. For a detailed characterization of the novelties associated with the current outbreak that would facilitate the accurate dissemination of information and policy-making, we performed a thorough literature search for MPVX infection on PubMed, Google Scholar, and Science Direct, using appropriate keywords to choose relevant articles.

Prevalence of foodborne and zoonotic viral pathogens in raw cow milk samples.

Foodborne and zoonotic viral pathogens are responsible for substantial morbidity and mortality worldwide. These viruses can be transmitted through foods such as dairy products to humans and cause several acute and chronic diseases. This study aimed to investigate the prevalence and profile of different foodborne and zoonotic viruses in raw cow milk samples. We collected 492 raw cow milk samples from local dairy markets in Qazvin, Iran. Then we evaluated the presence of hepatitis A virus, noroviruses, rotavirus, astrovirus, bovine leukaemia virus (BLV) and tick-borne encephalitis virus (TBEV) in samples using conventional and nested reverse transcription-polymerase chain reaction methods. We found that 34.95, 7.72, 25.81, 14.63, 66.86, 12.80 and 21.34% of raw milk samples were contaminated with norovirus GI, norovirus GII, hepatitis A virus, rotavirus, astrovirus, BLV and TBEV viruses, respectively. Interestingly, the samples collected from the city's south area revealed a higher prevalence of foodborne and zoonotic viruses. Astrovirus and its combination with norovirus GI were the most prevalent virus profiles. Also, the highest correlations were observed among the presence of rotavirus and hepatitis A viruses (0.36) and TBEV and norovirus GII (0.31). Considering the prevalence rate and virus profiles of different foodborne and zoonotic viruses in raw milk samples, hygiene practices and the pasteurization process are strongly suggested to be conducted throughout the cow milk production chain and in dairy industries to prevent infections with these pathogens.

Modern vaccine strategies for emerging zoonotic viruses.

INTRODUCTION: The significant increase in the emergence of notable zoonotic viruses in the previous decades has become a serious concern to global public health. Ninety-nine percent of infectious diseases have originated from zoonotic viruses with immense potential for dissemination, infecting the susceptible population completely lacking herd immunity. AREAS COVERED: Zoonotic viruses appear in the last two decades as a major health threat either newly evolved or previously present with elevated prevalence in the last few years are selected to explain their current prophylactic measures. In this review, modern generation vaccines including viral vector vaccines, mRNA vaccines, DNA vaccines, synthetic vaccines, virus-like particles, and plant-based vaccines are discussed with their benefits and challenges. Moreover, the traditional vaccines and their efficacy are also compared with the latest vaccines. EXPERT OPINION: The emergence and reemergence of viruses that constantly mutate themselves have greatly increased the chance of transmission and immune escape mechanisms in humans. Therefore, the only possible solution to prevent viral infection is the use of vaccines with improved safety profile and efficacy, which becomes the basis of modern generation vaccines.

Monkeypox 2022 Identify-Isolate-Inform: A 3I Tool for frontline clinicians for a zoonosis with escalating human community transmission.

Monkeypox 2022, a zoonotic virus similar to smallpox, presented as a rapidly escalating human outbreak with community transmission outside endemic regions of Africa. In just over one month of detection, confirmed cases escalated to over 3300, with reports of patients in at least 43 non-African nations. Mechanisms of transmission in animals and the reservoir host remain uncertain; spread from humans to wild or domestic animals risks the creation of new endemic zones. While initial cases were reported in men who have sex with men (MSM), monkeypox is not considered a sexually transmitted infection. Anyone with close contact with an infected person, aerosolized infectious material (e.g., from shaken bedsheets), or contact with fomites or infected animals is at risk. In humans, monkeypox typically presents with a non-specific prodromal phase followed by a classic rash with an incubation period of 5-21 days (usually 6-13 days). The prodrome may be subclinical, and the monkeypox virus may be transmissible from person-to-person before observed symptom onset. Most clinicians are unfamiliar with monkeypox. Information is rapidly evolving, producing an urgent need for immediate access to clear, concise, fact-based, and actionable information for frontline healthcare workers in prehospital, emergency departments/hospitals, and acute care/sexual transmitted infection clinics. This paper provides a novel Identify-Isolate-Inform (3I) Tool for the early detection and management of patients under investigation for monkeypox 2022. Patients are identified as potentially exposed or infected after an initial assessment of risk factors and signs/symptoms. Management of exposed patients includes consideration of quarantine and post-exposure prophylaxis with a smallpox vaccine. For infectious patients, providers must immediately don personal protective equipment and isolate patients. Healthcare workers must report suspected and confirmed cases in humans or animals to public health authorities. This innovative 3I Tool will assist emergency, primary care, and prehospital clinicians in effectively managing persons with suspected or confirmed monkeypox.

Major bat-borne zoonotic viral epidemics in Asia and Africa: A systematic review and meta-analysis.

Bats are the natural reservoir host for many pathogenic and non-pathogenic viruses, potentially spilling over to humans and domestic animals directly or via an intermediate host. The ongoing COVID-19 pandemic is the continuation of virus spillover events that have taken place over the last few decades, particularly in Asia and Africa. Therefore, these bat-associated epidemics provide a significant number of hints, including respiratory cellular tropism, more intense susceptibility to these cell types, and overall likely to become a pandemic for the next spillover. In this systematic review, we analysed data to insight, through bat-originated spillover in Asia and Africa. We used STATA/IC-13 software for descriptive statistics and meta-analysis. The random effect of meta-analysis showed that the pooled estimates of case fatality rates of bat-originated viral zoonotic diseases were higher in Africa (61.06%, 95%CI: 50.26 to 71.85, l2 % = 97.3, p < 0.001). Moreover, estimates of case fatality rates were higher in Ebola (61.06%; 95%CI: 50.26 to 71.85, l2 % = 97.3, p < 0.001) followed by Nipah (55.19%; 95%CI: 39.29 to 71.09, l2 % = 94.2, p < 0.001), MERS (18.49%; 95%CI: 8.19 to 28.76, l2 % = 95.4, p < 0.001) and SARS (10.86%; 95%CI: 6.02 to 15.71, l2 % = 85.7, p < 0.001) with the overall case fatality rates of 29.86 (95%CI: 29.97 to 48.58, l2 % = 99.0, p < 0.001). Bat-originated viruses have caused several outbreaks of deadly diseases, including Nipah, Ebola, SARS and MERS in Asia and Africa in a sequential fashion. Nipah virus emerged first in Malaysia, but later, periodic outbreaks were noticed in Bangladesh and India. Similarly, the Ebola virus was detected in the African continent with neurological disorders in humans, like Nipah, seen in the Asian region. Two important coronaviruses, MERS and SARS, were introduced, both with the potential to infect respiratory passages. This paper explores the dimension of spillover events within and/or between bat-human and the epidemiological risk factors, which may lead to another pandemic occurring. Further, these processes enhance the bat-originated virus, which utilises an intermediate host to jump into human species.

Unsupervised explainable AI for molecular evolutionary study of forty thousand SARS-CoV-2 genomes.

BACKGROUND: Unsupervised AI (artificial intelligence) can obtain novel knowledge from big data without particular models or prior knowledge and is highly desirable for unveiling hidden features in big data. SARS-CoV-2 poses a serious threat to public health and one important issue in characterizing this fast-evolving virus is to elucidate various aspects of their genome sequence changes. We previously established unsupervised AI, a BLSOM (batch-learning SOM), which can analyze five million genomic sequences simultaneously. The present study applied the BLSOM to the oligonucleotide compositions of forty thousand SARS-CoV-2 genomes. RESULTS: While only the oligonucleotide composition was given, the obtained clusters of genomes corresponded primarily to known main clades and internal divisions in the main clades. Since the BLSOM is explainable AI, it reveals which features of the oligonucleotide composition are responsible for clade clustering. Additionally, BLSOM also provided information concerning the special genomic region possibly undergoing RNA modifications. CONCLUSIONS: The BLSOM has powerful image display capabilities and enables efficient knowledge discovery about viral evolutionary processes, and it can complement phylogenetic methods based on sequence alignment.

Ranking the risk of animal-to-human spillover for newly discovered viruses.

The death toll and economic loss resulting from the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic are stark reminders that we are vulnerable to zoonotic viral threats. Strategies are needed to identify and characterize animal viruses that pose the greatest risk of spillover and spread in humans and inform public health interventions. Using expert opinion and scientific evidence, we identified host, viral, and environmental risk factors contributing to zoonotic virus spillover and spread in humans. We then developed a risk ranking framework and interactive web tool, SpillOver, that estimates a risk score for wildlife-origin viruses, creating a comparative risk assessment of viruses with uncharacterized zoonotic spillover potential alongside those already known to be zoonotic. Using data from testing 509,721 samples from 74,635 animals as part of a virus discovery project and public records of virus detections around the world, we ranked the spillover potential of 887 wildlife viruses. Validating the risk assessment, the top 12 were known zoonotic viruses, including SARS-CoV-2. Several newly detected wildlife viruses ranked higher than known zoonotic viruses. Using a scientifically informed process, we capitalized on the recent wealth of virus discovery data to systematically identify and prioritize targets for investigation. The publicly accessible SpillOver platform can be used by policy makers and health scientists to inform research and public health interventions for prevention and rapid control of disease outbreaks. SpillOver is a living, interactive database that can be refined over time to continue to improve the quality and public availability of information on viral threats to human health.

Human cell-dependent, directional, time-dependent changes in the mono- and oligonucleotide compositions of SARS-CoV-2 genomes.

BACKGROUND: When a virus that has grown in a nonhuman host starts an epidemic in the human population, human cells may not provide growth conditions ideal for the virus. Therefore, the invasion of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), which is usually prevalent in the bat population, into the human population is thought to have necessitated changes in the viral genome for efficient growth in the new environment. In the present study, to understand host-dependent changes in coronavirus genomes, we focused on the mono- and oligonucleotide compositions of SARS-CoV-2 genomes and investigated how these compositions changed time-dependently in the human cellular environment. We also compared the oligonucleotide compositions of SARS-CoV-2 and other coronaviruses prevalent in humans or bats to investigate the causes of changes in the host environment. RESULTS: Time-series analyses of changes in the nucleotide compositions of SARS-CoV-2 genomes revealed a group of mono- and oligonucleotides whose compositions changed in a common direction for all clades, even though viruses belonging to different clades should evolve independently. Interestingly, the compositions of these oligonucleotides changed towards those of coronaviruses that have been prevalent in humans for a long period and away from those of bat coronaviruses. CONCLUSIONS: Clade-independent, time-dependent changes are thought to have biological significance and should relate to viral adaptation to a new host environment, providing important clues for understanding viral host adaptation mechanisms.