scholarly journals Nipah virus in India: past, present and future

2018 ◽  
Vol 5 (9) ◽  
pp. 3653 ◽  
Author(s):  
Prarthana M. S.
Keyword(s):  
Environmental Changes ◽  
Nipah Virus ◽  
Case Fatality ◽  
Hendra Virus ◽  
High Morbidity ◽  
Surveillance Strategy ◽  
Rapid Urbanization ◽  
Highly Pathogenic ◽  
Effective Prevention ◽  
North East

Nipah virus (NiV) is one of the emerging highly pathogenic virus. Like Ebola and Zika viruses, NiV too is threatening the integrity of the mankind. The family Paramyxoviruses has been traditionally associated with a group of viruses with narrow host range and typically causes outbreaks with low mortality rates. But with the emergence of highly pathogenic Hendra virus and closely related NiV, they have evolved as a cause of fatal encephalitis across broad range of vertebrate species including humans. The natural reservoir of NiV is Pteropus bat, which is apparently distributed all over the South East Asia. The bat population from North East to North West states in India have NiV antibodies which mean there is active NiV infection among Indian bats. As NiV is associated with high morbidity and mortality they pose a risk from natural outbreaks, laboratory accidents or deliberate misuse. The development of effective prevention and treatment strategies is very crucial. Preparedness, surveillance, constant vigil needs to be carried out continuously in the country. The present outbreak in India after nearly eleven years with a high case fatality rate indicate that there is a total lack of health care systems preparedness and surveillance strategy. The anthropogenic and environmental changes occurring due to rapid urbanization and massive deforestation has made India now even more vulnerable for such recurrent outbreaks. This review highlights the changing trend of the NiV outbreaks in the past and the current outbreak in India.

scholarly journals Evaluation of a Single-Dose Nucleoside-Modified Messenger RNA Vaccine Encoding Hendra Virus-Soluble Glycoprotein Against Lethal Nipah virus Challenge in Syrian Hamsters

2019 ◽  
Vol 221 (Supplement_4) ◽  
pp. S493-S498 ◽  
Author(s):  
Michael K Lo ◽  
Jessica R Spengler ◽  
Stephen R Welch ◽  
Jessica R Harmon ◽  
JoAnn D Coleman-McCray ◽  
...  
Keyword(s):  
Single Dose ◽  
Immune Responses ◽  
Messenger Rna ◽  
Nipah Virus ◽  
Hendra Virus ◽  
Highly Pathogenic ◽  
Syrian Hamsters ◽  
Virus Challenge ◽  
Pathogenic Viruses ◽  
Rna Vaccine

Abstract In the absence of approved vaccines and therapeutics for use in humans, Nipah virus (NiV) continues to cause fatal outbreaks of encephalitis and respiratory disease in Bangladesh and India on a near-annual basis. We determined that a single dose of a lipid nanoparticle nucleoside-modified messenger RNA vaccine encoding the soluble Hendra virus glycoprotein protected up to 70% of Syrian hamsters from lethal NiV challenge, despite animals having suboptimally primed immune responses before challenge. These data provide a foundation from which to optimize future messenger RNA vaccination studies against NiV and other highly pathogenic viruses.

scholarly journals Heparan Sulfate-Dependent Enhancement of Henipavirus Infection

mBio ◽  
2015 ◽  
Vol 6 (2) ◽  
Author(s):  
Cyrille Mathieu ◽  
Kévin P. Dhondt ◽  
Marie Châlons ◽  
Stéphane Mély ◽  
Hervé Raoul ◽  
...  
Keyword(s):  
Heparan Sulfate ◽  
Anticoagulant Activity ◽  
Antiviral Treatment ◽  
Mammalian Species ◽  
Nipah Virus ◽  
Hendra Virus ◽  
Host Cells ◽  
Emerging Infections ◽  
Highly Pathogenic

ABSTRACTNipah virus and Hendra virus are emerging, highly pathogenic, zoonotic paramyxoviruses that belong to the genusHenipavirus. They infect humans as well as numerous mammalian species. Both viruses use ephrin-B2 and -B3 as cell entry receptors, and following initial entry into an organism, they are capable of rapid spread throughout the host. We have previously reported that Nipah virus can use another attachment receptor, different from its entry receptors, to bind to nonpermissive circulating leukocytes, thereby promoting viral dissemination within the host. Here, this attachment molecule was identified as heparan sulfate for both Nipah virus and Hendra virus. Cells devoid of heparan sulfate were not able to mediate henipavirustrans-infection and showed reduced permissivity to infection. Virus pseudotyped with Nipah virus glycoproteins bound heparan sulfate and heparin but no other glycosaminoglycans in a surface plasmon resonance assay. Furthermore, heparin was able to inhibit the interaction of the viruses with the heparan sulfate and to block cell-mediatedtrans-infection of henipaviruses. Moreover, heparin was shown to bind to ephrin-B3 and to restrain infection of permissive cellsin vitro. Consequently, treatment with heparin devoid of anticoagulant activity improved the survival of Nipah virus-infected hamsters. Altogether, these results reveal heparan sulfate as a new attachment receptor for henipaviruses and as a potential therapeutic target for the development of novel approaches against these highly lethal infections.IMPORTANCETheHenipavirusgenus includes two closely related, highly pathogenic paramyxoviruses, Nipah virus and Hendra virus, which cause elevated morbidity and mortality in animals and humans. Pathogenesis of both Nipah virus and Hendra virus infection is poorly understood, and efficient antiviral treatment is still missing. Here, we identified heparan sulfate as a novel attachment receptor used by both viruses to bind host cells. We demonstrate that heparin was able to inhibit the interaction of the viruses with heparan sulfate and to block cell-mediatedtrans-infection of henipaviruses. Moreover, heparin also bound to the viral entry receptor and thereby restricted infection of permissive cellsin vitro. Consequently, heparin treatment improved survival of Nipah virus-infected hamsters. These results uncover an important role of heparan sulfate in henipavirus infection and open novel perspectives for the development of heparan sulfate-targeting therapeutic approaches for these emerging infections.

scholarly journals Vaccines to Emerging Viruses: Nipah and Hendra

2020 ◽  
Vol 7 (1) ◽  
pp. 447-473
Author(s):  
Moushimi Amaya ◽  
Christopher C. Broder
Keyword(s):  
Vaccine Development ◽  
Severe Disease ◽  
Mammalian Species ◽  
Nipah Virus ◽  
Case Fatality ◽  
Hendra Virus ◽  
Emerging Viruses ◽  
Research Focus ◽  
Pandemic Threat ◽  
Made In

Hendra virus (HeV) and Nipah virus (NiV) are bat-borne zoonotic para-myxoviruses identified in the mid- to late 1990s in outbreaks of severe disease in livestock and people in Australia and Malaysia, respectively. HeV repeatedly re-emerges in Australia while NiV continues to cause outbreaks in South Asia (Bangladesh and India), and these viruses have remained transboundary threats. In people and several mammalian species, HeV and NiV infections present as a severe systemic and often fatal neurologic and/or respiratory disease. NiV stands out as a potential pandemic threat because of its associated high case-fatality rates and capacity for human-to-human transmission. The development of effective vaccines, suitable for people and livestock, against HeV and NiV has been a research focus. Here, we review the progress made in NiV and HeV vaccine development, with an emphasis on those approaches that have been tested in established animal challenge models of NiV and HeV infection and disease.

scholarly journals Agricultural intensification, priming for persistence and the emergence of Nipah virus: a lethal bat-borne zoonosis

2011 ◽  
Vol 9 (66) ◽  
pp. 89-101 ◽  
Author(s):  
Juliet R. C. Pulliam ◽  
Jonathan H. Epstein ◽  
Jonathan Dushoff ◽  
Sohayati A. Rahman ◽  
Michel Bunning ◽  
...  
Keyword(s):  
Southern Oscillation ◽  
Nipah Virus ◽  
Case Fatality ◽  
Climatic Conditions ◽  
Emerging Pathogens ◽  
Effective Prevention ◽  
Infection Dynamics ◽  
Index Site ◽  
Analyse Data ◽  
Human Infections

Emerging zoonoses threaten global health, yet the processes by which they emerge are complex and poorly understood. Nipah virus (NiV) is an important threat owing to its broad host and geographical range, high case fatality, potential for human-to-human transmission and lack of effective prevention or therapies. Here, we investigate the origin of the first identified outbreak of NiV encephalitis in Malaysia and Singapore. We analyse data on livestock production from the index site (a commercial pig farm in Malaysia) prior to and during the outbreak, on Malaysian agricultural production, and from surveys of NiV's wildlife reservoir (flying foxes). Our analyses suggest that repeated introduction of NiV from wildlife changed infection dynamics in pigs. Initial viral introduction produced an explosive epizootic that drove itself to extinction but primed the population for enzootic persistence upon reintroduction of the virus. The resultant within-farm persistence permitted regional spread and increased the number of human infections. This study refutes an earlier hypothesis that anomalous El Niño Southern Oscillation-related climatic conditions drove emergence and suggests that priming for persistence drove the emergence of a novel zoonotic pathogen. Thus, we provide empirical evidence for a causative mechanism previously proposed as a precursor to widespread infection with H5N1 avian influenza and other emerging pathogens.

scholarly journals A structural basis for antibody-mediated neutralization of Nipah virus reveals a site of vulnerability at the fusion glycoprotein apex

2019 ◽  
Vol 116 (50) ◽  
pp. 25057-25067 ◽  
Author(s):  
Victoria A. Avanzato ◽  
Kasopefoluwa Y. Oguntuyo ◽  
Marina Escalera-Zamudio ◽  
Bernardo Gutierrez ◽  
Michael Golden ◽  
...  
Keyword(s):  
Host Cell ◽  
Cell Attachment ◽  
Nipah Virus ◽  
Case Fatality ◽  
Neutralizing Antibody ◽  
Distal Region ◽  
Hendra Virus ◽  
Structural Basis ◽  
Specific Sequence ◽  
A Site

Nipah virus (NiV) is a highly pathogenic paramyxovirus that causes frequent outbreaks of severe neurologic and respiratory disease in humans with high case fatality rates. The 2 glycoproteins displayed on the surface of the virus, NiV-G and NiV-F, mediate host-cell attachment and membrane fusion, respectively, and are targets of the host antibody response. Here, we provide a molecular basis for neutralization of NiV through antibody-mediated targeting of NiV-F. Structural characterization of a neutralizing antibody (nAb) in complex with trimeric prefusion NiV-F reveals an epitope at the membrane-distal domain III (DIII) of the molecule, a region that undergoes substantial refolding during host-cell entry. The epitope of this monoclonal antibody (mAb66) is primarily protein-specific and we observe that glycosylation at the periphery of the interface likely does not inhibit mAb66 binding to NiV-F. Further characterization reveals that a Hendra virus-F–specific nAb (mAb36) and many antibodies in an antihenipavirus-F polyclonal antibody mixture (pAb835) also target this region of the molecule. Integrated with previously reported paramyxovirus F−nAb structures, these data support a model whereby the membrane-distal region of the F protein is targeted by the antibody-mediated immune response across henipaviruses. Notably, our domain-specific sequence analysis reveals no evidence of selective pressure at this region of the molecule, suggestive that functional constraints prevent immune-driven sequence variation. Combined, our data reveal the membrane-distal region of NiV-F as a site of vulnerability on the NiV surface.

scholarly journals Immune Serum Produced by DNA Vaccination Protects Hamsters against Lethal Respiratory Challenge with Andes Virus

2007 ◽  
Vol 82 (3) ◽  
pp. 1332-1338 ◽  
Author(s):  
Jay W. Hooper ◽  
Anthony M. Ferro ◽  
Victoria Wahl-Jensen
Keyword(s):  
Dna Vaccine ◽  
Neutralizing Antibodies ◽  
Lethal Dose ◽  
Case Fatality ◽  
Immune Serum ◽  
Human Infection ◽  
M Gene ◽  
Hamster Model ◽  
Highly Pathogenic ◽  
Andes Virus

ABSTRACT Hantavirus pulmonary syndrome (HPS) is a highly pathogenic disease (40% case fatality rate) carried by rodents chronically infected with certain viruses within the genus Hantavirus of the family Bunyaviridae. The primary mode of transmission to humans is thought to be inhalation of excreta from infected rodents; however, ingestion of contaminated material and rodent bites are also possible modes of transmission. Person-to-person transmission of HPS caused by one species of hantavirus, Andes virus (ANDV), has been reported. Previously, we reported that ANDV injected intramuscularly causes a disease in Syrian hamsters that closely resembles HPS in humans. Here we tested whether ANDV was lethal in hamsters when it was administered by routes that more accurately model the most common routes of human infection, i.e., the subcutaneous, intranasal, and intragastric routes. We discovered that ANDV was lethal by all three routes. Remarkably, even at very low doses, ANDV was highly pathogenic when it was introduced by the mucosal routes (50% lethal dose [LD50], ∼100 PFU). We performed passive transfer experiments to test the capacity of neutralizing antibodies to protect against lethal intranasal challenge. The neutralizing antibodies used in these experiments were produced in rabbits vaccinated by electroporation with a previously described ANDV M gene-based DNA vaccine, pWRG/AND-M. Hamsters that were administered immune serum on days −1 and +5 relative to challenge were protected against intranasal challenge (21 LD50). These findings demonstrate the utility of using the ANDV hamster model to study transmission across mucosal barriers and provide evidence that neutralizing antibodies produced by DNA vaccine technology can be used to protect against challenge by the respiratory route.

scholarly journals Social Evaluation of Public Open Space Services and Their Impact on Well-Being: A Micro-Scale Assessment from a Coastal University

2021 ◽  
Vol 13 (8) ◽  
pp. 4372
Author(s):  
Abdullah Addas ◽  
Ahmad Maghrabi
Keyword(s):  
Open Space ◽  
Environmental Changes ◽  
Positive Impact ◽  
Well Being ◽  
Social Evaluation ◽  
Open Spaces ◽  
Rapid Urbanization ◽  
Public Open Space ◽  
The Impact ◽  
Public Open Spaces

Public open spaces services have been shown to be profoundly affected by rapid urbanization and environmental changes, and in turn, they have influenced socio-cultural relationships and human well-being. However, the impact of these changes on public open space services (POSS) remains unexplored, particularly in the Saudi Arabian context. This study examines the socio-cultural influence of POSS on the King Abdulaziz University campus, Jeddah, Saudi Arabia and the impact of these services on well-being. A field survey and questionnaire were used to collect data. Non-parametric tests (Kruskal–Wallis and Mann–Whitney tests) were used to find significant differences in the importance of POSS as perceived by stakeholders based on socio-demographic attributes. Factor analysis was performed for 14 POSS to identify those that are most important. The study showed that (i) university stakeholders are closely linked to services provided by public open spaces (POS) and dependent on POSS, (ii) there were significant differences in the perceived importance of POSS according to gender, age, and social groups, and (iii) 70 to 90% of stakeholders reported POSS as having a positive impact on well-being. Thus, the findings will help design and plan POSS to meet the needs of society and promote well-being.

scholarly journals Fc-Based Recombinant Henipavirus Vaccines Elicit Broad Neutralizing Antibody Responses in Mice

Viruses ◽  
2020 ◽  
Vol 12 (4) ◽  
pp. 480 ◽  
Author(s):  
Yaohui Li ◽  
Ruihua Li ◽  
Meirong Wang ◽  
Yujiao Liu ◽  
Ying Yin ◽  
...  
Keyword(s):  
Antibody Response ◽  
Fusion Protein ◽  
G Protein ◽  
G Proteins ◽  
Hendra Virus ◽  
Antibody Responses ◽  
Asia Pacific ◽  
Highly Pathogenic ◽  
Bivalent Vaccine ◽  
Tetravalent Vaccine

The genus Henipavirus (HNVs) includes two fatal viruses, namely Nipah virus (NiV) and Hendra virus (HeV). Since 1994, NiV and HeV have been endemic to the Asia–Pacific region and responsible for more than 600 cases of infections. Two emerging HNVs, Ghana virus (GhV) and Mojiang virus (MojV), are speculated to be associated with unrecognized human diseases in Africa and China, respectively. Despite many efforts to develop vaccines against henipaviral diseases, there is presently no licensed human vaccine. As HNVs are highly pathogenic and diverse, it is necessary to develop universal vaccines to prevent future outbreaks. The attachment enveloped glycoprotein (G protein) of HNVs mediates HNV attachment to the host cell’s surface receptors. G proteins have been used as a protective antigen in many vaccine candidates for HNVs. We performed quantitative studies on the antibody responses elicited by the G proteins of NiV, HeV, GhV, and MojV. We found that the G proteins of NiV and HeV elicited only a limited cross-reactive antibody response. Further, there was no cross-protection between MojV, GhV, and highly pathogenic HNVs. We then constructed a bivalent vaccine where the G proteins of NiV and HeV were fused with the human IgG1 Fc domain. The immunogenicity of the bivalent vaccine was compared with that of monovalent vaccines. Our results revealed that the Fc-based bivalent vaccine elicited a potent antibody response against both NiV and HeV. We also constructed a tetravalent Fc heterodimer fusion protein that contains the G protein domains of four HNVs. Immunization with the tetravalent vaccine elicited broad antibody responses against NiV, HeV, GhV, and MojV in mice, indicating compatibility among the four antigens in the Fc-fusion protein. These data suggest that our novel bivalent and tetravalent Fc-fusion proteins may be efficient candidates to prevent HNV infection.

scholarly journals Mutations in the PA Protein of Avian H5N1 Influenza Viruses Affect Polymerase Activity and Mouse Virulence

2017 ◽  
pp. JVI.01557-17 ◽  
Author(s):  
Gongxun Zhong ◽  
Mai Quynh Le ◽  
Tiago J.S. Lopes ◽  
Peter Halfmann ◽  
Masato Hatta ◽  
...  
Keyword(s):  
Amino Acid ◽  
Case Fatality ◽  
Polymerase Activity ◽  
Influenza Viruses ◽  
Viral Polymerase ◽  
Highly Pathogenic ◽  
H5n1 Influenza ◽  
Increased Risk ◽  
Severe Infections ◽  
Viral Determinants

To study the influenza viral determinants of pathogenicity, we characterized two highly pathogenic avian H5N1 influenza viruses isolated in Vietnam in 2012 (A/duck/Vietnam/QT1480/2012; QT1480) and 2013 (A/duck/Vietnam/QT1728/2013; QT1728) and found that the activity of their polymerase complexes differed significantly, even though both viruses were highly pathogenic in mice. Further studies revealed that the PA-S343A/E347D mutations reduced viral polymerase activity and mouse virulence when tested in the genetic background of QT1728 virus. In contrast, the PA-343S/347E mutations increased the polymerase activity of QT1480 and the virulence of a low pathogenic H5N1 influenza virus. The PA-343S residue (which alone increased viral polymerase activity and mouse virulence significantly relative to viral replication complexes encoding PA-343A) is frequently found in H5N1 influenza viruses of several subclades; infection with a virus possessing this amino acid may pose an increased risk to humans.IMPORTANCEH5N1 influenza viruses cause severe infections in humans with a case fatality rate that exceeds 50%. The factors that determine the high virulence of these viruses in humans are not fully understood. Here, we identified two amino acid changes in the viral polymerase PA protein that affect the activity of the viral polymerase complex and virulence in mice. Infection with viruses possessing these amino acid changes may pose an increased risk to humans.

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