ETIDIOH - NEW

ABSTRACT Betacoronaviruses, which have caused three human outbreaks within the last two decades, are thought to originate from bats , raising the concern that bat coronaviruses could cause a novel human outbreak in the future. To determine whether the bat merbecovirus EjCoV-3 strain , previously detected in Eptesicus japonensis in Japan , has the potential to infect humans, we analyzed its cellular entry mechanism. Cellular entry of EjCoV-3 via the spike protein requires protease treatment and is mediated by an unknown receptor, other than DPP4 or ACE2 . We generated cultivable recombinant EjCoV-3 using bacterial artificial chromosome-based reverse genetics and found that it efficiently replicated in human respiratory and intestinal cell cultures as well as nasal ciliated epithelium in hamsters. These findings suggest that bat merbecovirus with ACE2- and DPP4-independent cell entry has the potential to cause human infections , highlighting the importance of extensive bat surveillance f...

Abstract Bats are the natural reservoirs for a variety of emerging and re-emerging viruses. Among them, rabies virus (genus Lyssavirus, family Rhabdoviridae) is one of the first and most emblematic described in these animals. Since its first description, several new bat lyssaviruses have been regularly identified. In addition to lyssaviruses, other bat rhabdoviruses have also been discovered, including members of the genera Vesiculovirus , Ledantevirus and, more recently, Alphanemrhavirus and Tupavirus . However, the family Rhabdoviridae is one of the most abundant and diverse viral families, with 434 officially recognized species , divided into 5 subfamilies and 56 different genera . The number of rhabdoviruses associated with bats is therefore probably higher than that currently available. In this study, we first developed and validated a combined nested RT-qPCR technique (pan-rhabdo RT-nqPCR) dedicated to the broad detection of animal rhabdoviruses. After validation, this technique ...

Abstract Despite accumulating evidence that bat-derived coronaviruses often require intermediate hosts to facilitate transmission to humans1, the potential role of fur animals in zoonotic coronavirus spillovers has largely been overlooked2. Here we report the isolation and characterization of a novel mink respiratory coronavirus (MRCoV) from farmed minks with pneumonia . Notably, MRCoV uses angiotensin-converting enzyme 2 (ACE2) as a receptor and can infect mink, bat, monkey, and human cells . Cryo-electron microscopy analysis revealed that the MRCoV receptor-binding domain (RBD) binds to the same interface on ACE2 receptors as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RBD , despite exhibiting notable structural differences. We identify the key determinants on ACE2 and MRCoV RBD that confer efficient binding. HKU5-33S, a bat coronavirus closely related to MRCoV , utilizes ACE2 of bat Pipistrellus abramus and requires only two amino acid substitutions to adapt to mink...

Abstract Prior to the discovery of bat influenza A virus (IAV) subtypes H17N10 and H18N11 , all IAVs were thought to bind sialic acid residues via hemagglutinin (HA) to mediate attachment and subsequent viral entry. However, H17 and H18 engage a proteinaceous receptor : the major histocompatibility complex class II (MHCII). The mechanistic details of this hitherto unknown protein-mediated entry are not understood. Given that conventional IAVs rely on multivalent binding to sialylated glycans , we hypothesized that bat HA similarly interacts with multiple MHCII molecules. Using photoactivated localization microscopy (PALM) on fixed and live cells, we demonstrate that bat IAV particles attach to pre-existing MHCII clusters and induce a further increase in cluster size upon binding. To measure the impact of viral attachment on the dynamics of MHCII, we employ an “inverse attachment” approach, immobilizing viral particles on coverslips before seeding live MHCII-expressing cells on top. Sin...

Abstract We performed serologic surveillance for selected arthropod-borne viruses (arboviruses) in bats and opossums in the Lacandona Rainforest, Chiapas, Mexico , in 2023–2024. Sera were collected from 94 bats of at least 15 species and 43 opossums of three species. The sera were assayed by the plaque reduction neutralization test (PRNT) for antibodies to eight orthoflaviviruses ( dengue viruses 1–4, St. Louis encephalitis virus , T’Ho virus, West Nile virus, and Zika virus ) and one alphavirus (chikungunya virus; CHIKV). Twelve (12.8%) bats and 15 (34.9%) opossums contained orthoflavivirus-specific antibodies . One bat (a Jamaican fruit bat) was seropositive for Zika virus , and 11 bats contained antibodies to an undetermined orthoflavivirus , as did the 15 opossums. All bats and most opossums seropositive for an undetermined orthoflavivirus had low PRNT titers, possibly because they had been infected with another (perhaps unrecognized) orthoflavivirus not included in the PRNTs. Anti...

Abstract Circulating bat coronaviruses present a significant pandemic threat, yet our  understanding of  their genetic diversity and evolutionary dynamics remains limited.  Over 3 years, we sampled  1,462 bats in Cambodia’s Steung Treng province,  identifying extensive and diverse  coronaviruses co-circulation. Using  metatranscriptomic and amplicon sequencing, we  generated 33 complete  sarbecovirus genomes, revealing novel lineages that cluster into four  distinct  groups, each associated with different Rhinolophus bat species. Our analysis  highlights rapid migration and recombination of sarbecovirus lineages over  short distances  and timescales. Of note, the receptor-binding domains of two novel  viral groups exhibit high  similarity to SARS-CoV-2, and pseudovirus assays  confirmed the ability of this spike protein  to mediate entry into cells expressing  human ACE2, suggesting a potentia...

Abstract SARS-like betacoronaviruses (sarbecoviruses) endemic in bats pose a significant zoonotic threat to humans . Genetic pathways associated with spillover of bat sarbecoviruses into humans are incompletely understood. We previously showed that the WT spike of the rhinolophid bat coronavirus SHC014 -CoV has poor entry activity and uncovered two distinct genetic pathways outside the receptor-binding domain (RBD) that increased spike opening, ACE2 binding , and cell entry. Herein, we show that the widely studied bat sarbecovirus WIV1-CoV is likely a cell culture-adapted variant of Rs3367-CoV, which was sequenced from the same population of rhinolophid bats as SHC014-CoV. We demonstrate that the acquisition of a single amino-acid substitution in the ‘630-loop’ of the S1 subunit was the key spike adaptation event during the successful isolation of WIV1-CoV, and that it enhances spike opening, virus-receptor recognition, and cell entry in much the same manner as the substitutions we pre...

Abstract We report 1.3% (19/1,511) of Egyptian rousette bats (ERBs) in Uganda and Sierra Leone were co-infected with different combinations of Marburg, Sosuga, Kasokero, or Yogue viruses . To prevent infection by those viruses, we recommend avoiding ERB-populated areas, avoiding ERBs and ERB-contaminated objects, and thoroughly washing harvested fruits before consumption. Source: US Centers for Disease Control and Prevention,  https://wwwnc.cdc.gov/eid/article/31/5/24-1669_article ____

Abstract Most human emerging infectious diseases are zoonotic , originating in animal hosts prior to spillover to humans . Prioritizing the surveillance of wildlife that overlaps with humans and human activities can increase the likelihood of detecting viruses with a high potential for human infection. Here, we obtained fecal swabs from two fruit bat species —Eidolon helvum (n = 6) and Epomophorus wahlbergi (n = 43) (family Pteropodidae)— in peridomestic habitats in Nairobi, Kenya , and used metagenome sequencing to detect microorganisms. A near-complete genome of a novel virus assigned taxonomically to the Coronaviridae family Betacoronavirus genus and Nobecovirus subclade was characterized from E. wahlbergi. Phylogenetic analysis indicates this unique Nobecovirus clade shares a common ancestor with Eidolon/Rousettus Nobecovirus subclades isolated from Madagascar, Kenya, and Cameroon . Recombination was detected across open reading frames, except the spike protein, in all BOOTSCAN ana...

Abstract Ebola virus (EBOV) and Marburg virus (MARV) are zoonotic filoviruses that cause hemorrhagic fever in humans . Correlative data implicate bats as natural EBOV hosts , but neither a full-length genome nor an EBOV isolate has been found in any bats sampled. Here, we model filovirus infection in the Jamaican fruit bat (JFB), Artibeus jamaicensis, by inoculation with either EBOV or MARV through a combination of oral, intranasal, and subcutaneous routes . Infection with EBOV results in systemic virus replication and oral shedding of infectious virus. MARV replication is transient and does not shed. In vitro, JFB cells replicate EBOV more efficiently than MARV, and MARV infection induces innate antiviral responses that EBOV efficiently suppresses. Experiments using VSV pseudoparticles or replicating VSV expressing the EBOV or MARV glycoprotein demonstrate an advantage for EBOV entry and replication early , respectively, in JFB cells. Overall, this study describes filovirus species-sp...

Abstract Influenza viruses are highly capable of mutating and adapting in mammalian hosts . While these viruses have been extensively studied in birds, research on their presence in bats has been limited. However, influenza viruses circulating in bats have shown notable molecular divergence . The present study aimed to characterize the phylogenetic, evolutionary, and antigenic relationships of an influenza A virus detected in the fishing bat Noctilio albiventris . As part of a pathogen surveillance study of public health interest, 159 rectal samples were collected from bats in the Colombian Caribbean . The samples were sequenced using RNA-Seq. A genome (eight viral contigs) associated with the Orthomyxoviridae family was identified in a pool. Most segments showed approximately 90% similarity with H18N11, except for the neuraminidase. Analysis of the N protein shows that occupies a basal position relative to the N11 subtype, with its divergence date estimated to be approximately 50 year...

Abstract Henipaviruses, such as Hendra and Nipah viruses, are major zoonotic pathogens that cause encephalitis and respiratory infections in humans and animals . The recent emergence of Langya virus in China highlights the need to understand henipavirus host diversity and geographic spread to prevent future outbreaks. Our analysis of the National Center for Biotechnology Information Virus and VIRION databases revealed ≈1,117 henipavirus sequences and 142 complete genomes. Bats (64.7%) and shrews (11.7%) dominated the host species record, and the genera Pteropus and Crocidura contained key henipavirus hosts in Asia, Australia, and Africa . Henipaviruses found in the Eidolon bat genus exhibited the highest within-host genetic distance. Phylogenetic analysis revealed batborne and rodent- or shrew-derived henipaviruses diverged ≈11,000 years ago and the first known lineage originating in Eidolon genus bats ≈9,900 years ago. Pathogenic henipaviruses diverged from their ancestors 2,800–1,200...

Highlights •   A distinct HKU5 coronavirus lineage (HKU5-CoV-2) is discovered in bats •  Bat HKU5-CoV-2 uses human ACE2 receptor and ACE2 orthologs from multiple species •   Bat HKU5-CoV-2 RBD engages human ACE2 with a distinct binding mode from other CoVs •  Bat HKU5-CoV-2 was isolated and infect human-ACE2-expressing cells Summary Merbecoviruses comprise four viral species with remarkable genetic diversity: MERS -related coronavirus, Tylonycterisbat coronavirus HKU4, Pipistrellusbat coronavirus HKU5, and Hedgehog coronavirus 1. However, the potential human spillover risk of animal merbecoviruses remains to be investigated. Here, we reported the discovery of HKU5-CoV lineage 2 (HKU5-CoV-2) in bats that efficiently utilize human angiotensin-converting enzyme 2 (ACE2) as a functional receptor and exhibits a broad host tropism . Cryo-EM analysis of HKU5-CoV-2 receptor-binding domain (RBD) and human ACE2 complex revealed an entirely distinct binding mode compared with o...