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The genus Henipavirus in the family Paramyxoviridae contains two viruses, Hendra virus (HeV) and Nipah virus (NiV) for which pteropid bats act as the main natural reservoir. Each virus also causes serious and commonly lethal infection of people as well as various species of domestic animals, however little is known about the associated mechanisms of pathogenesis. Here, we report the isolation and characterization of a new paramyxovirus from pteropid bats, Cedar virus (CedPV), which shares significant features with the known henipaviruses. The genome size (18,162 nt) and organization of CedPV is very similar to that of HeV and NiV; its nucleocapsid protein displays antigenic cross-reactivity with henipaviruses; and it uses the same receptor molecule (ephrin-B2) for entry during infection. Preliminary challenge studies with CedPV in ferrets and guinea pigs, both susceptible to infection and disease with known henipaviruses, confirmed virus replication and production of neutralizing antibodies although clinical disease was not observed. In this context, it is interesting to note that the major genetic difference between CedPV and HeV or NiV lies within the coding strategy of the P gene, which is known to play an important role in evading the host innate immune system. Unlike HeV, NiV, and almost all known paramyxoviruses, the CedPV P gene lacks both RNA editing and also the coding capacity for the highly conserved V protein. Preliminary study indicated that CedPV infection of human cells induces a more robust IFN-β response than HeV.

RNA metagenomic analysis of tissues from 4 wild-caught northern short-tailed shrews in Alabama, USA, revealed a novel henipavirus (family Paramyxoviridae). Phylogenetic analysis supported the placement of the virus within the shrew henipavirus clade, related to human-infecting shrewborne henipaviruses. Our study results highlight the presence of henipavirus infections in North America.

We describe isolation and characterization of a novel henipavirus, designated Salt Gully virus, from the urine of pteropid bats in Australia. We noted the virus to be most closely related to Angavokely virus, not reliant on ephrin receptors for cell entry, and of unknown risk for human disease.

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 years ago. Including atypical hosts and regions in future investigations is necessary to control future outbreaks.

Bats are natural reservoirs for a wide range of microorganisms, including many notable zoonotic pathogens. However, the composition of the infectome (i.e., the collection of viral, bacterial and eukaryotic microorganisms) within bat kidneys remains poorly understood. To address this gap, we performed meta-transcriptomic sequencing on kidney tissues from 142 bats, spanning ten species sampled at five locations in Yunnan province, China. This analysis identified 22 viral species, including 20 novel viruses, two of which represented newly discovered henipaviruses closely related to the highly pathogenic Hendra and Nipah viruses. These henipaviruses were found in the kidneys of bats inhabiting an orchard near villages, raising concerns about potential fruit contamination via bat urine and transmission risks to livestock or humans. Additionally, we identified a novel protozoan parasite, tentatively named Klossiella yunnanensis , along with two highly abundant bacterial species, one of which is a newly discovered species— Flavobacterium yunnanensis . These findings broaden our understanding of the bat kidney infectome, underscore critical zoonotic threats, and highlight the need for comprehensive, full-spectrum microbial analyses of previously understudied organs to better assess spillover risks from bat populations.

Hendra virus (HeV) and Nipah virus (NiV) are closely related, recently emerged paramyxoviruses that form Henipavirus genus and are capable of causing considerable morbidity and mortality in a number of mammalian species, including humans. However, in contrast to many other species and despite expression of functional virus entry receptors, mice are resistant to henipavirus infection. We report here the susceptibility of mice deleted for the type I interferon receptor (IFNAR-KO) to both HeV and NiV. Intraperitoneally infected mice developed fatal encephalitis, with pathology and immunohistochemical features similar to what was found in humans. Viral RNA was found in the majority of analyzed organs, and sublethally infected animals developed virus-specific neutralizing antibodies. Altogether, these results reveal IFNAR-KO mice as a new small animal model to study HeV and NiV pathogenesis, prophylaxis, and treatment and suggest the critical role of type I interferon signaling in the control of henipavirus infection.

Background Hendra virus and Nipah virus are zoonotic viruses that have caused severe to fatal disease in livestock and human populations. The isolation of Cedar virus, a non-pathogenic virus species in the genus Henipavirus , closely-related to the highly pathogenic Hendra virus and Nipah virus offers an opportunity to investigate differences in pathogenesis and receptor tropism among these viruses. Methods We constructed full-length cDNA clones of Cedar virus from synthetic oligonucleotides and rescued two replication-competent, recombinant Cedar virus variants: a recombinant wild-type Cedar virus and a recombinant Cedar virus that expresses a green fluorescent protein from an open reading frame inserted between the phosphoprotein and matrix genes. Replication kinetics of both viruses and stimulation of the interferon pathway were characterized in vitro. Cellular tropism for ephrin-B type ligands was qualitatively investigated by microscopy and quantitatively by a split-luciferase fusion assay. Results Successful rescue of recombinant Cedar virus expressing a green fluorescent protein did not significantly affect virus replication compared to the recombinant wild-type Cedar virus. We demonstrated that recombinant Cedar virus stimulated the interferon pathway and utilized the established Hendra virus and Nipah virus receptor, ephrin-B2, but not ephrin-B3 to mediate virus entry. We further characterized virus-mediated membrane fusion kinetics of Cedar virus with the known henipavirus receptors ephrin-B2 and ephrin-B3. Conclusions The recombinant Cedar virus platform may be utilized to characterize the determinants of pathogenesis across the henipaviruses, investigate their receptor tropisms, and identify novel pan-henipavirus antivirals. Moreover, these experiments can be conducted safely under BSL-2 conditions.

Background Bats and rodents have been identified as reservoirs for several highly pathogenic and zoonotic viruses including henipaviruses, a genus within the Paramyxoviridae family. A number of studies have revealed the circulation of henipaviruses at the wildlife-human-livestock interface in Cameroon. In this study, we describe the molecular analysis as well as the development and evaluation of a Bead-based Multiplex Binding Assay (BMBA) using an in-house Indirect Enzyme Linked Immunosorbent Assay (ELISA) to confirm the detection of henipavirus infection in wildlife species. Results A total of 600 fruit bats and 600 rodents were sampled between March 2018 and June 2020. Samples were analyzed using a semi-nested RT-PCR assay followed by sequencing of the PCR fragments. Transudates (754) were screened for the presence of henipavirus-specific antibodies in a BMBA and confirmed by ELISA using Hendra virus (HeV), Nipah virus (NiV) and Ghana virus (GhV) glycoproteins expressed in Leishmania tarentolae , and commercially available HeV G and NiV G glycoproteins. Henipavirus-specific antibodies were detected in 19/531 (3.6%) bat transudates screened by BMBA and confirmed by ELISA. Seroprevalence rates in the Centre and North Regions were 12/291 (4.1%) and 7/240 (2.9%) respectively. All rodents and shrews were serologically negative. Henipavirus RNA sequences were not detected in any of the samples screened in this work. Conclusion This study provides further data supporting the circulation of Henipaviruses in fruit bats ( Eidolon helvum ) which are roosting and reproducing in proximity to human and livestock populations in the Centre and North Regions of Cameroon. This also establishes the first detection of Henipavirus specific antibodies in Eidolon helvum populations in the North Region of Cameroon.

Henipaviruses are emerging zoonotic viruses that have caused deadly outbreaks in humans and livestock across several regions of the world. The fusion (F) protein of henipaviruses plays a critical role in viral entry into host cells and represents a key determinant of viral pathogenicity. This review provides a comprehensive analysis of current knowledge regarding trafficking, activation, as well as the role in particle assembly, of henipavirus F proteins. We discuss the unique characteristics of henipavirus F proteins compared to other paramyxovirus fusion proteins, with particular emphasis on their distinctive trafficking and activation mechanisms. Attention is also given to novel henipaviruses that have been detected in hosts other than bats, namely rodents and shrews. These viruses are sufficiently different that the International Committee on Taxonomy of Viruses has proposed a new genus for them, the Parahenipaviruses. We discuss how variations in F protein characteristics between Henipaviruses, Parahenipaviruses, and yet-unclassified henipa-like viruses might influence their trafficking and activation. Understanding these molecular mechanisms is crucial for developing effective therapeutic strategies against henipavirus infections and for predicting the emergence of novel henipavirus strains with pandemic potential.

Paramyxoviruses, negative-sense single-stranded RNA viruses, pose a critical threat to human public health. Currently, 78 species, 17 genera, and 4 subfamilies of paramyxoviruses are harbored by multiple natural reservoirs, including rodents, bats, birds, reptiles, and fish. Henipaviruses are critical zoonotic pathogens that cause severe acute respiratory distress and neurological diseases in humans. Using reverse transcription-polymerase chain reaction, 115 Crocidura species individuals were examined for the prevalence of paramyxovirus infections. Paramyxovirus RNA was observed in 26 (22.6%) shrews collected at five trapping sites, Republic of Korea. Herein, we report two genetically distinct novel paramyxoviruses (genus: Henipavirus): Gamak virus (GAKV) and Daeryong virus (DARV) isolated from C. lasiura and C. shantungensis, respectively. Two GAKVs and one DARV were nearly completely sequenced using next-generation sequencing. GAKV and DARV contain six genes (3′-N-P-M-F-G-L-5′) with genome sizes of 18,460 nucleotides and 19,471 nucleotides, respectively. The phylogenetic inference demonstrated that GAKV and DARV form independent genetic lineages of Henipavirus in Crocidura species. GAKV-infected human lung epithelial cells elicited the induction of type I/III interferons, interferon-stimulated genes, and proinflammatory cytokines. In conclusion, this study contributes further understandings of the molecular prevalence, genetic characteristics and diversity, and zoonotic potential of novel paramyxoviruses in shrews.