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Nature Reviews. Microbiology Aug 2020Most viral pathogens in humans have animal origins and arose through cross-species transmission. Over the past 50 years, several viruses, including Ebola virus, Marburg... (Review)
Review
Most viral pathogens in humans have animal origins and arose through cross-species transmission. Over the past 50 years, several viruses, including Ebola virus, Marburg virus, Nipah virus, Hendra virus, severe acute respiratory syndrome coronavirus (SARS-CoV), Middle East respiratory coronavirus (MERS-CoV) and SARS-CoV-2, have been linked back to various bat species. Despite decades of research into bats and the pathogens they carry, the fields of bat virus ecology and molecular biology are still nascent, with many questions largely unexplored, thus hindering our ability to anticipate and prepare for the next viral outbreak. In this Review, we discuss the latest advancements and understanding of bat-borne viruses, reflecting on current knowledge gaps and outlining the potential routes for future research as well as for outbreak response and prevention efforts.
Topics: Animals; Biodiversity; Chiroptera; Communicable Diseases, Emerging; Disease Outbreaks; Humans; Research; Virus Diseases; Virus Physiological Phenomena; Zoonoses
PubMed: 32528128
DOI: 10.1038/s41579-020-0394-z -
Journal of Clinical Microbiology Jun 2018Nipah virus, a paramyxovirus related to Hendra virus, first emerged in Malaysia in 1998. Clinical presentation ranges from asymptomatic infection to fatal encephalitis.... (Review)
Review
Nipah virus, a paramyxovirus related to Hendra virus, first emerged in Malaysia in 1998. Clinical presentation ranges from asymptomatic infection to fatal encephalitis. Malaysia has had no more cases since 1999, but outbreaks continue to occur in Bangladesh and India. In the Malaysia-Singapore outbreak, transmission occurred primarily through contact with pigs, whereas in Bangladesh and India, it is associated with ingestion of contaminated date palm sap and human-to-human transmission. Bats are the main reservoir for this virus, which can cause disease in humans and animals. There are currently no effective therapeutics, and supportive care and prevention are the mainstays of management.
Topics: Abattoirs; Animals; Bangladesh; Chiroptera; Disease Outbreaks; Disease Reservoirs; Encephalitis; Henipavirus Infections; History, 20th Century; History, 21st Century; Humans; India; Malaysia; Nipah Virus; Phoeniceae; Singapore; Swine
PubMed: 29643201
DOI: 10.1128/JCM.01875-17 -
Virulence Dec 2023Paramyxoviruses are a family of single-stranded negative-sense RNA viruses, many of which are responsible for a range of respiratory and neurological diseases in humans... (Review)
Review
Paramyxoviruses are a family of single-stranded negative-sense RNA viruses, many of which are responsible for a range of respiratory and neurological diseases in humans and animals. Among the most notable are the henipaviruses, which include the deadly Nipah (NiV) and Hendra (HeV) viruses, the causative agents of outbreaks of severe disease and high case fatality rates in humans and animals. NiV and HeV are maintained in fruit bat reservoirs primarily in the family and spillover into humans directly or by an intermediate amplifying host such as swine or horses. Recently, non-chiropteran associated Langya (LayV), Gamak (GAKV), and Mojiang (MojV) viruses have been discovered with confirmed or suspected ability to cause disease in humans or animals. These viruses are less genetically related to HeV and NiV yet share many features with their better-known counterparts. Recent advances in surveillance of wild animal reservoir viruses have revealed a high number of henipaviral genome sequences distributed across most continents, and mammalian orders previously unknown to harbour henipaviruses. In this review, we summarize the current knowledge on the range of pathogenesis observed for the henipaviruses as well as their replication cycle, epidemiology, genomics, and host responses. We focus on the most pathogenic viruses, including NiV, HeV, LayV, and GAKV, as well as the experimentally non-pathogenic CedV. We also highlight the emerging threats posed by these and potentially other closely related viruses.
Topics: Animals; Humans; Swine; Horses; Virulence; Henipavirus Infections; Nipah Virus; Hendra Virus; Disease Outbreaks; Chiroptera
PubMed: 37948320
DOI: 10.1080/21505594.2023.2273684 -
Cell Jul 2022Stem cell research endeavors to generate specific subtypes of classically defined "cell types." Here, we generate >90% pure human artery or vein endothelial cells from...
Stem cell research endeavors to generate specific subtypes of classically defined "cell types." Here, we generate >90% pure human artery or vein endothelial cells from pluripotent stem cells within 3-4 days. We specified artery cells by inhibiting vein-specifying signals and vice versa. These cells modeled viral infection of human vasculature by Nipah and Hendra viruses, which are extraordinarily deadly (∼57%-59% fatality rate) and require biosafety-level-4 containment. Generating pure populations of artery and vein cells highlighted that Nipah and Hendra viruses preferentially infected arteries; arteries expressed higher levels of their viral-entry receptor. Virally infected artery cells fused into syncytia containing up to 23 nuclei, which rapidly died. Despite infecting arteries and occupying ∼6%-17% of their transcriptome, Nipah and Hendra largely eluded innate immune detection, minimally eliciting interferon signaling. We thus efficiently generate artery and vein cells, introduce stem-cell-based toolkits for biosafety-level-4 virology, and explore the arterial tropism and cellular effects of Nipah and Hendra viruses.
Topics: Arteries; Endothelial Cells; Hendra Virus; Humans; Nipah Virus; Pluripotent Stem Cells; Tropism
PubMed: 35738284
DOI: 10.1016/j.cell.2022.05.024 -
Proceedings of the National Academy of... Oct 2022Feline morbillivirus (FeMV) is a recently discovered pathogen of domestic cats and has been classified as a morbillivirus in the family. We determined the complete...
Feline morbillivirus (FeMV) is a recently discovered pathogen of domestic cats and has been classified as a morbillivirus in the family. We determined the complete sequence of FeMV directly from an FeMV-positive urine sample without virus isolation or cell passage. Sequence analysis of the viral genome revealed potential divergence from characteristics of archetypal morbilliviruses. First, the virus lacks the canonical polybasic furin cleavage signal in the fusion (F) glycoprotein. Second, conserved amino acids in the hemagglutinin (H) glycoprotein used by all other morbilliviruses for binding and/or fusion activation with the cellular receptor CD150 (signaling lymphocyte activation molecule [SLAM]/F1) are absent. We show that, despite this sequence divergence, FeMV H glycoprotein uses feline CD150 as a receptor and cannot use human CD150. We demonstrate that the protease responsible for cleaving the FeMV F glycoprotein is a cathepsin, making FeMV a unique morbillivirus and more similar to the closely related zoonotic Nipah and Hendra viruses. We developed a reverse genetics system for FeMV and generated recombinant viruses expressing Venus fluorescent protein from an additional transcription unit located either between the phospho-protein () and matrix () genes or the and large () genes of the genome. We used these recombinant FeMVs to establish a natural infection and demonstrate that FeMV causes an acute morbillivirus-like disease in the cat. Virus was shed in the urine and detectable in the kidneys at later time points. This opens the door for long-term studies to address the postulated role of this morbillivirus in the development of chronic kidney disease.
Topics: Amino Acids; Animals; Cathepsins; Cats; Furin; Hemagglutinins; Humans; Kidney; Morbillivirus; Morbillivirus Infections
PubMed: 36251995
DOI: 10.1073/pnas.2209405119 -
Current Opinion in Virology Feb 2018The genus Henipavirus has expanded rapidly in geographic range, number of species, and host range. Hendra and Nipah virus are two henipaviruses known to cause severe... (Review)
Review
The genus Henipavirus has expanded rapidly in geographic range, number of species, and host range. Hendra and Nipah virus are two henipaviruses known to cause severe disease in humans with a high case-fatality rate. Pteropid spp. bats are the natural reservoir of Hendra and Nipah virus. From these bats, virus can be transmitted to an amplifying host, horses and pigs, and from these hosts to humans, or the virus can be transmitted directly to humans. Although the main route of shedding varies between host species, close contact is required for transmission in all hosts. Understanding the transmission routes of Hendra and Nipah virus in their respective hosts is essential for devising strategies to block zoonotic transmission.
Topics: Animals; Chiroptera; Disease Reservoirs; Hendra Virus; Henipavirus Infections; Horses; Host Specificity; Humans; Nipah Virus; Swine; Virus Shedding; Zoonoses
PubMed: 29035743
DOI: 10.1016/j.coviro.2017.09.004 -
Viruses Sep 2023Hendra virus (HeV) and Nipah virus (NiV) are zoonotic paramyxoviruses in the genus (HNV) that emerged nearly thirty years ago. Outbreaks of HeV and NiV have led to... (Review)
Review
Hendra virus (HeV) and Nipah virus (NiV) are zoonotic paramyxoviruses in the genus (HNV) that emerged nearly thirty years ago. Outbreaks of HeV and NiV have led to severe respiratory disease and encephalitis in humans and animals characterized by a high mortality rate. Despite the grave threat HNVs pose to public health and global biosecurity, no approved medical countermeasures for human use currently exist against HeV or NiV. To develop candidate vaccines and therapeutics and advance the field's understanding of HNV pathogenesis, animal models of HeV and NiV have been instrumental and remain indispensable. Various species, including rodents, ferrets, and nonhuman primates (NHPs), have been employed for HNV investigations. Among these, NHPs have demonstrated the closest resemblance to human HNV disease, although other animal models replicate some key disease features. Here, we provide a comprehensive review of the currently available animal models (mice, hamsters, guinea pigs, ferrets, cats, dogs, nonhuman primates, horses, and swine) to support HNV research. We also discuss the strengths and limitations of each model for conducting pathogenesis and transmission studies on HeV and NiV and for the evaluation of medical countermeasures.
Topics: Cricetinae; Animals; Humans; Guinea Pigs; Horses; Mice; Dogs; Ferrets; Henipavirus Infections; Hendra Virus; Nipah Virus; Disease Models, Animal; Primates
PubMed: 37896758
DOI: 10.3390/v15101980 -
Pathogens (Basel, Switzerland) Nov 2022Nipah and Hendra viruses are deadly zoonotic paramyxoviruses with a case fatality rate of upto 75%. The viruses belong to the genus henipavirus in the family , a family... (Review)
Review
Nipah and Hendra viruses are deadly zoonotic paramyxoviruses with a case fatality rate of upto 75%. The viruses belong to the genus henipavirus in the family , a family of negative-sense single-stranded RNA viruses. The natural reservoirs of NiV and HeV are bats (flying foxes) in which the virus infection is asymptomatic. The intermediate hosts for NiV and HeV are swine and equine, respectively. In humans, NiV infections result in severe and often fatal respiratory and neurological manifestations. The Nipah virus was first identified in Malaysia and Singapore following an outbreak of encephalitis in pig farmers and subsequent outbreaks have been reported in Bangladesh and India almost every year. Due to its extreme pathogenicity, pandemic potential, and lack of established antiviral therapeutics and vaccines, research on henipaviruses is highly warranted so as to develop antivirals or vaccines that could aid in the prevention and control of future outbreaks.
PubMed: 36558753
DOI: 10.3390/pathogens11121419