Bat Virus Research Articles

Exposure to Zoonotic West Nile Virus in Long-Tailed Macaques and Bats in Peninsular Malaysia.

Simple SummaryThe role of wildlife animals, such as macaques and bats, in the spreading and maintenance of deadly zoonotic pathogens in nature are documented in several studies. The present study substantially highlights the first evidence of West Nile Virus (WNV) infection, a mosquito borne virus in the Malaysian macaques and bats. Of the 81 macaques sampled, 24 of the long-tailed macaques were seropositive to WNV, indicating that they were exposed to the virus in the past. The long-tailed macaques were found in the mangrove forests located in the Central, Southern, and West Peninsular Malaysia. Meanwhile, five out of 41 bats (Lesser Short-nosed Fruit Bats, Lesser Sheath-tailed Bats, and Thai Horseshoe Bats) that were found in the caves from Northern Peninsular Malaysia showed susceptibility to WNV. Therefore, a constant bio surveillance of WNV in the wildlife in Malaysia is a proactive attempt. This study was aligned with the Malaysian government’s mission under the Malaysia Strategy for Emerging Diseases and Public Health Emergencies (MYSED) II (2017–2021) and the Ministry of Health priorities in order to enhance the regional capability to rapidly and accurately survey, detect, diagnose, and report outbreaks of pathogens and diseases of security concern.The role of wildlife such as wild birds, macaques, and bats in the spreading and maintenance of deadly zoonotic pathogens in nature have been well documented in many parts of the world. One such pathogen is the mosquitoes borne virus, namely the West Nile Virus (WNV). Previous research has shown that 1:7 and 1:6 Malaysian wild birds are WNV antibody and RNA positive, respectively, and bats in North America may not be susceptible to the WNV infection. This study was conducted to determine the status of WNV in Malaysian macaques and bats found in mangrove forests and caves, respectively. Archive sera and oropharyngeal swabs from long-tailed macaques were subjected to the antibody detection using WNV competitive enzyme-linked immunosorbent assay (c-ELISA) and WNV RNA using RT-PCR, respectively, while the archive oropharyngeal and rectal swabs from bats were subjected to RT-PCR without serological analysis due to the unavailability of serum samples. The analysis revealed a WNV seropositivity of 29.63% (24/81) and none of the macaques were positive for WNV RNA. Meanwhile, 12.2% (5/41) of the bats from Pteropodidae, Emballonuridae, and Rhinolophidae families tested positive for WNV RNA. Here, we show a high WNV antibody prevalence in macaques and a moderate WNV RNA in various Malaysian bat species, suggesting that WNV circulates through Malaysian wild animals and Malaysian bat species may be susceptible to the WNV infection.

On the role of viruses in nature and what this means for the COVID-19 pandemic.

On the role of viruses in nature and what this means for the COVID-19 pandemic.

Antigenic variation of SARS-CoV-2 in response to immune pressure.

Analysis of the bat viruses most closely related to SARS‐CoV‐2 indicated that the virus probably required limited adaptation to spread in humans. Nonetheless, since its introduction in human populations, SARS‐CoV‐2 must have been subject to the selective pressure imposed by the human immune system. We exploited the availability of a large number of high‐quality SARS‐CoV‐2 genomes, as well as of validated epitope predictions, to show that B cell epitopes in the spike glycoprotein (S) and in the nucleocapsid protein (N) have higher diversity than nonepitope positions. Similar results were obtained for other human coronaviruses and for sarbecoviruses sampled in bats. Conversely, in the SARS‐CoV‐2 population, epitopes for CD4+ and CD8+ T cells were not more variable than nonepitope positions. A significant reduction in epitope variability was instead observed for some of the most immunogenic proteins (S, N, ORF8 and ORF3a). Analysis over longer evolutionary time frames indicated that this effect is not due to differential constraints. These data indicate that SARS‐CoV‐2 evolves to elude the host humoral immune response, whereas recognition by T cells is not actively avoided by the virus. However, we also found a trend of lower diversity of T cell epitopes for common cold coronaviruses, indicating that epitope conservation per se is not directly linked to disease severity. We suggest that conservation serves to maintain epitopes that elicit tolerizing T cell responses or induce T cells with regulatory activity.

Incidence of Viruses in Neotropical Bats

The diversity of bat species and some of their distinct biological and ecological characteristics contribute to their wide distribution, being generally abundant and common in a variety of habitats, factors that can influence their association with different emerging and reemerging viruses. Studies have shown that bats have characteristics which contribute to the evolution of a unique set of antiviral immune responses that control the replication of viruses, such as their gregarious social organization and ability to fly. In this paper we review the incidence of viruses in Neotropical bats, and the role of species as hosts or vectors of these diseases. A total of 110 species belonging to seven families were found to have been detected carrying virus in the region. Although Chiroptera is the second most diverse order of mammals, the diversity of bat-hosted viruses has only recently come into focus, as the result of improved wildlife surveillance. Diverse viruses have been detected in bats, however, in the majority of the cases, there is no evidence that the virus is transmitted from bats to other animals or causes disease in humans.

Lyssaviruses in Insectivorous Bats, South Africa, 2003-2018.

We detected 3 lyssaviruses in insectivorous bats sampled in South Africa during 2003–2018. We used phylogenetic analysis to identify Duvenhage lyssavirus and a potentially new lyssavirus, provisionally named Matlo bat lyssavirus, that is related to West Caucasian bat virus. These new detections highlight that much about lyssaviruses remains unknown.

The Potential of Rats and Bats as Reservoirs of Leptospirosis and Japanese Encephalitis (JE) in Muna Region, Southeast Sulawesi Province, Indonesia

BACKGROUND: Small mammals such as rats and bats are important animal reservoirs of various zoonotic diseases of public health importance. The potential of rats and bats as a reservoir of leptospirosis and Japanese Encephalitis (JE) in Muna Regency remains unknown. This study aimed to determine the presence of Leptospira spp and JE virus (JEV) in rats and bats in Muna Regency, Southeast Sulawesi Province.
 
 METHODS: A cross-sectional survey was carried out in three districts, namely Kabawo, Batalaiworu, and Katobu. Bats and rats were caught in six ecosystems spread across the three districts. Serological (Microscopic Agglutination Test, MAT) and molecular examinations (Polymerase Chain Reactions, PCR) were performed to detect Leptospira spp. and JEV in rats and bats, respectively. 
 
 RESULTS: A total of 137 rats from seven species were successfully caught, namely Mus sp., Rattus argentiventer, R. nitidus, R. exulans, R. hoffmanni, R. norvegicus, and R. tanezumi. Of which, six species were confirmed positive for Leptospira spp by PCR, with the highest prevalence was found in R. argentiventer (50%) and R. tanezumi (36.4%). Meanwhile, a total of 86 bats were also successfully captured. The JEV antibody was detected in D. viridis, R. celebensis and S. wallacei. 
 
 CONCLUSION: Rats and bats are the potential reservoirs of leptospirosis and JE in Muna Regency. Most importantly, the study provides the first evidence of JE reservoirs (R. celebensis and S. wallacei) in Sulawesi. Surveillance of leptospirosis and JE are recommended. 

The Viral Zoonotic Diseases from bats

Bats are known reservoirs of virulent zoonotic pathogens not known to experience disease. They are known as nature’s pest controllers which are insectivorous and pollinators which are frugivorous in their nature. In the entire ecosystem bats play a vital role in various ways to sustain the diversity at its best. However, recent events have cast great aspersions on the bat behavior and the potential impact it has on Public Health not just in a specified region but globally. The impact has been devastating and disastrous. The recent COVID 19 pandemic spell, opened the eyes of the scientific community, economists and even governments to work together.
 A host of issues were brought to light, as to how viral pathogenicity has played havoc with such virulence in the world community. Numerous studies proved beyond doubt bats act as natural reservoirs for a large number of emerging and re emerging pathogens that other animals and humans can contract. It would be surprising to know that these viruses are also listed in the bioterrorism list of pathogens. Such diversity shows that the bats are well adapted to the effects of virulent pathogens within their internal milieu. The first report of transmission of a bat virus to human was reported in 1960, it was the Rabies virus belonging to the Lyssa virus genus. SARS, Ebola, Nipah have already proven to be virulent and lethal.(1)
 
 AIM
 To ascertain the viral dynamics in bats that lead to rapid transmission and infectivity in humans
 Objectives
 To understand the characteristics that bats possess, to host virulent pathogens
 To outline the mechanisms in bats in causing rapid transmission to humans

Catalogue of bat viruses (2020)

Aim. Aim of this the research presented in this article is to analyze the representation of bat (Chiroptera) viruses in various taxa of the Virae kingdom.Discussion. Currently, 260 viruses are associated with bats belonging to 19 orders, 28 families (9 DNA‐containing and 19 RNA‐containing) and 61 genera (18 DNA‐containing and 43 RNA‐containing). This number includes viruses annotated by the International Committee on the Taxonomy of Viruses (excluding synonymous species) for which the taxonomic status has been verified by sequencing subgenomic or full‐genomic nucleotide sequences. A large number of unidentified strains from bats are noteworthy – they apparently contain many future prototype viruses for new taxa.Conclusion. The data presented in this article will undoubtedly be expanded in the nearest future. This is due to the need to improve the system for prevention of dangerous epidemic and pandemic situations primarily by increasing priority attention on bat viruses. Therefore, the catalogue of bat viruses, known as of mid‐2020, presented in this paper could be considered as a kind of "starting point" for future research in this area.

On the Evolution of Virulent Zoonotic Viruses in Bats

Ideas formulated by Paul Ewald about the “evolution of virulence” are used to explain why bats, more often than other mammals, are a reservoir of virulent viruses, and why many of these viruses severely affect other mammals, including humans, but are apparently less pathogenic for bats. Potential factors contributing to bat viruses often being zoonotic are briefly discussed.

Corona Virus- An Overview

Coronavirus disease 19 (COVID-19) is a highly communicable and pathogenic viral infection caused bythe severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that has developed in Wuhan, Chinaand spread all over the world.Genomic analysis revealed that SARS-CoV-2 is phylogenetically associatedwith severe, acute respiratory syndrome-like (SARS-like) bat viruses, so bats could be the primary reservoirpossible. The intermediate source of origin and human transfer is unknown, but the accelerated human tohuman transmission has been widely confirmed.Maximal precautionary steps and resources have also beenput forwardby most nations to mitigate transmission and decrease mortality rates.

Review of the Corona Viruses Causing Acute Respiratory Syndrome and COVID-2019 (COVID-19) Pandemic

A new virus, Severe Acute Respiratory Syndrome Corona Virus-2 (SARS CoV-2) emerged in December 2019 and still continuing to pose a great threat all over the Globe claiming to a fatality 980,031 persons. Among the human corona viruses it is the third one causing acute respiratory distress syndrome. The others two are SARS CoV and MERS CoV. The objective of this study is to review the human corona viruses causing severe respiratory distresses which are detected thru analysis of some recently published documents on the deadly SARS CoV-2 as well as information on SARS-CoV and MERS CoV from different world class trust worthy reliable and dependable sources. Genetic analysis reveals that the new human corona virus (SARS CoV-2) has similarities with the severe acute respiratory syndrome like (SARS like) bat virus which thought to be the primary reservoir. SARSCoV and MERS-CoV also have same bat reservoir but the intermediate host are different for three human corona viruses. Though the clinical picture is more or less similar but efficiency of human to human transmission is not same for these viruses. So, strict control measures are critical to contain this very big pandemic been occurring since December 2019. Everyday new information has been coming causing strategy to change to control this pandemic. Zoonotic origin of corona viruses indicate researchers, public health specialists should keep the continuous surveillance for early detection of new virus alike SARS –CoV-2.International Journal of Human and Health Sciences Vol. 05 No. 02 April’21 Page: 139-147

Different tertiary interactions create the same important 3D features in a distinct flavivirus xrRNA.

During infection by a flavivirus (FV), cells accumulate noncoding subgenomic flavivirus RNAs (sfRNAs) that interfere with several antiviral pathways. These sfRNAs are formed by structured RNA elements in the 3′ untranslated region (UTR) of the viral genomic RNA, which block the progression of host cell exoribonucleases that have targeted the viral RNA. Previous work on these exoribonuclease-resistant RNAs (xrRNAs) from mosquito-borne FVs revealed a specific three-dimensional fold with a unique topology in which a ring-like structure protectively encircles the 5′ end of the xrRNA. Conserved nucleotides make specific tertiary interactions that support this fold. Examination of more divergent FVs reveals differences in their 3′ UTR sequences, raising the question of whether they contain xrRNAs and if so, how they fold. To answer this, we demonstrated the presence of an authentic xrRNA in the 3′ UTR of the Tamana bat virus (TABV) and solved its structure by X-ray crystallography. The structure reveals conserved features from previously characterized xrRNAs, but in the TABV version these features are created through a novel set of tertiary interactions not previously seen in xrRNAs. This includes two important A–C interactions, four distinct backbone kinks, several ordered Mg2+ ions, and a C+–G–C base triple. The discovery that the same overall architecture can be achieved by very different sequences and interactions in distantly related flaviviruses provides insight into the diversity of this type of RNA and will inform searches for undiscovered xrRNAs in viruses and beyond.

Evolutionary Arms Race between Virus and Host Drives Genetic Diversity in Bat Severe Acute Respiratory Syndrome-Related Coronavirus Spike Genes.

The Chinese horseshoe bat (Rhinolophus sinicus), reservoir host of severe acute respiratory syndrome coronavirus (SARS-CoV), carries many bat SARS-related CoVs (SARSr-CoVs) with high genetic diversity, particularly in the spike gene. Despite these variations, some bat SARSr-CoVs can utilize the orthologs of the human SARS-CoV receptor, angiotensin-converting enzyme 2 (ACE2), for entry. It is speculated that the interaction between bat ACE2 and SARSr-CoV spike proteins drives diversity. Here, we identified a series of R. sinicus ACE2 variants with some polymorphic sites involved in the interaction with the SARS-CoV spike protein. Pseudoviruses or SARSr-CoVs carrying different spike proteins showed different infection efficiencies in cells transiently expressing bat ACE2 variants. Consistent results were observed by binding affinity assays between SARS-CoV and SARSr-CoV spike proteins and receptor molecules from bats and humans. All tested bat SARSr-CoV spike proteins had a higher binding affinity to human ACE2 than to bat ACE2, although they showed a 10-fold lower binding affinity to human ACE2 compared with that of their SARS-CoV counterpart. Structure modeling revealed that the difference in binding affinity between spike and ACE2 might be caused by the alteration of some key residues in the interface of these two molecules. Molecular evolution analysis indicates that some key residues were under positive selection. These results suggest that the SARSr-CoV spike protein and R. sinicus ACE2 may have coevolved over time and experienced selection pressure from each other, triggering the evolutionary arms race dynamics.IMPORTANCE Evolutionary arms race dynamics shape the diversity of viruses and their receptors. Identification of key residues which are involved in interspecies transmission is important to predict potential pathogen spillover from wildlife to humans. Previously, we have identified genetically diverse SARSr-CoVs in Chinese horseshoe bats. Here, we show the highly polymorphic ACE2 in Chinese horseshoe bat populations. These ACE2 variants support SARS-CoV and SARSr-CoV infection but with different binding affinities to different spike proteins. The higher binding affinity of SARSr-CoV spike to human ACE2 suggests that these viruses have the capacity for spillover to humans. The positive selection of residues at the interface between ACE2 and SARSr-CoV spike protein suggests long-term and ongoing coevolutionary dynamics between them. Continued surveillance of this group of viruses in bats is necessary for the prevention of the next SARS-like disease.

A New Subclass of Exoribonuclease-Resistant RNA Found in Multiple Genera of Flaviviridae.

Viruses have developed innovative strategies to exploit the cellular machinery and overcome the antiviral defenses of the host, often using specifically structured RNA elements. Examples are found in the Flavivirus genus (in the family Flaviviridae), where during flaviviral infection, pathogenic subgenomic flaviviral RNAs (sfRNAs) accumulate in the cell. These sfRNAs are formed when a host cell 5' to 3' exoribonuclease degrades the viral genomic RNA but is blocked by an exoribonuclease-resistant RNA structure (xrRNA) located in the viral genome's 3' untranslated region (UTR). Although known to exist in several Flaviviridae genera, the full distribution and diversity of xrRNAs in this family were unknown. Using the recently solved high-resolution structure of an xrRNA from the divergent flavivirus Tamana bat virus (TABV) as a reference, we used bioinformatic searches to identify xrRNAs in the remaining three genera of Flaviviridae: Pegivirus, Pestivirus, and Hepacivirus We biochemically and structurally characterized several examples, determining that they are genuine xrRNAs with a conserved fold. These new xrRNAs look superficially similar to the previously described xrRNAs but possess structural differences making them distinct from previous classes of xrRNAs. Overall, we have identified the presence of xrRNA in all four genera of Flaviviridae, but not in all species. Our findings thus require adjustments of previous xrRNA classification schemes and expand the previously known distribution of xrRNA in Flaviviridae.IMPORTANCE The members of the Flaviviridae comprise one of the largest families of positive-sense single-stranded RNA (+ssRNA) and are divided into the Flavivirus, Pestivirus, Pegivirus, and Hepacivirus genera. The genus Flavivirus contains many medically relevant viruses such as Zika virus, dengue virus, and Powassan virus. In these, a part of the RNA of the virus twists up into a distinct three-dimensional shape called an exoribonuclease-resistant RNA (xrRNA) that blocks the ability of the cell to "chew up" the viral RNA. Hence, part of the RNA of the virus remains intact, and this protected part is important for viral infection. These xrRNAs were known to occur in flaviviruses, but whether they existed in the other members of the family was not known. In this study, we identified a new subclass of xrRNA found not only in flaviviruses but also in the remaining three genera. The fact that these structured viral RNAs exist throughout the Flaviviridae family suggests they are important parts of the infection strategy of diverse pathogens, which could lead to new avenues of research.

Evolutionary origins of the SARS-CoV-2 sarbecovirus lineage responsible for the COVID-19 pandemic.

There are outstanding evolutionary questions on the recent emergence of human coronavirus SARS-CoV-2 including the role of reservoir species, the role of recombination and its time of divergence from animal viruses. We find that the sarbecoviruses-the viral subgenus containing SARS-CoV and SARS-CoV-2-undergo frequent recombination and exhibit spatially structured genetic diversity on a regional scale in China. SARS-CoV-2 itself is not a recombinant of any sarbecoviruses detected to date, and its receptor-binding motif, important for specificity to human ACE2 receptors, appears to be an ancestral trait shared with bat viruses and not one acquired recently via recombination. To employ phylogenetic dating methods, recombinant regions of a 68-genome sarbecovirus alignment were removed with three independent methods. Bayesian evolutionary rate and divergence date estimates were shown to be consistent for these three approaches and for two different prior specifications of evolutionary rates based on HCoV-OC43 and MERS-CoV. Divergence dates between SARS-CoV-2 and the bat sarbecovirus reservoir were estimated as 1948 (95% highest posterior density (HPD): 1879-1999), 1969 (95% HPD: 1930-2000) and 1982 (95% HPD: 1948-2009), indicating that the lineage giving rise to SARS-CoV-2 has been circulating unnoticed in bats for decades.

NPC1 as a Modulator of Disease Severity and Viral Entry of SARSCoV- 2.

The COVID-19 plague is hitting mankind. Several viruses, including SARS-CoV-1, MERS-CoV, EBOV, and SARS-CoV-2, use the endocytic machinery to enter the cell. Genomic variants in NPC1, which encodes for the endo-lysosomal Niemann-Pick type C1 protein, restricts the host-range of viruses in bats and susceptibility to infections in humans. Lack of NPC1 and its pharmacological suppression inhibits many viral infections including SARS-CoV-1 and Type I Feline Coronavirus Infection. Antiviral effects of NPC1-inhibiting drugs for COVID-19 treatment should be explored.

SARS-CoV-2 and bat RaTG13 spike glycoprotein structures inform on virus evolution and furin-cleavage effects.

SARS-CoV-2 is thought to have emerged from bats, possibly via a secondary host. Here, we investigate the relationship of spike (S) glycoprotein from SARS-CoV-2 with the S protein of a closely related bat virus, RaTG13. We determined cryo-EM structures for RaTG13 S and for both furin-cleaved and uncleaved SARS-CoV-2 S; we compared these with recently reported structures for uncleaved SARS-CoV-2 S. We also biochemically characterized their relative stabilities and affinities for the SARS-CoV-2 receptor ACE2. Although the overall structures of human and bat virus S proteins are similar, there are key differences in their properties, including a more stable precleavage form of human S and about 1,000-fold tighter binding of SARS-CoV-2 to human receptor. These observations suggest that cleavage at the furin-cleavage site decreases the overall stability of SARS-CoV-2 S and facilitates the adoption of the open conformation that is required for S to bind to the ACE2 receptor.

A viral infection explanation for Kawasaki disease in general and for COVID-19 virus-related Kawasaki disease symptoms.

SARS-CoV-2, a new virus that appeared in Wuhan, China, in 2019 has approximately an 80% genomic match to the Severe Acute Respiratory Symptom (SARS) virus, which is known to come from a bat virus. Symptoms of Kawasaki disease in general and incomplete Kawasaki disease have been seen in a subset of pediatric patients having a current or previous infection of SARS-CoV-2. A viral infection, such as a SARS-CoV-2 virus infection, could result in extensive antigen–antibody immune complexes that cannot be quickly cleared in a subset of patients and thus create a type III hypersensitivity immune reaction and cause Kawasaki disease or Kawasaki disease symptoms (also known as multisystem inflammatory syndrome) in a subset of patients. Extensive binding of antibodies to viral antigens can create antigen–antibody immune complexes, which, if not eliminated in certain individuals having dysfunctional complement systems, can start inflammatory type III hypersensitivity symptoms, including protease releases that can disrupt epithelium, mesothelium, and endothelium basement membranes, and induce pervasive inflammation throughout the body. This could continue after SARS-CoV-2 infections end if the first wave of protease attacks on basement membranes created new secondary autoantibodies and new uncleared antigen–antibody immune complexes.

SARS-COV-2 and biomimetics: What saves the planet will save our health.

SARS-COV-2 and biomimetics: What saves the planet will save our health.

Bat and Lyssavirus Exposure among Humans in Area that Celebrates Bat Festival, Nigeria, 2010 and 2013.

Using questionnaires and serologic testing, we evaluated bat and lyssavirus exposure among persons in an area of Nigeria that celebrates a bat festival. Bats from festival caves underwent serologic testing for phylogroup II lyssaviruses (Lagos bat virus, Shimoni bat virus, Mokola virus). The enrolled households consisted of 2,112 persons, among whom 213 (10%) were reported to have ever had bat contact (having touched a bat, having been bitten by a bat, or having been scratched by a bat) and 52 (2%) to have ever been bitten by a bat. Of 203 participants with bat contact, 3 (1%) had received rabies vaccination. No participant had neutralizing antibodies to phylogroup II lyssaviruses, but >50% of bats had neutralizing antibodies to these lyssaviruses. Even though we found no evidence of phylogroup II lyssavirus exposure among humans, persons interacting with bats in the area could benefit from practicing bat-related health precautions.