henipavirus

File:Henipavirus structure.svg

File:Henipavirus genome.png

Henipavirions are pleomorphic (variably shaped), ranging in size from 40 to 600 nm in diameter.{{cite journal |vauthors=Hyatt AD, Zaki SR, Goldsmith CS, Wise TG, Hengstberger SG |title=Ultrastructure of Hendra virus and Nipah virus within cultured cells and host animals |journal=Microbes and Infection |volume=3 |issue=4 |pages=297–306 |year=2001 |pmid=11334747 |doi= 10.1016/S1286-4579(01)01383-1}} They possess a lipid membrane overlying a shell of viral matrix protein. At the core is a single helical strand of genomic RNA tightly bound to N (nucleocapsid) protein and associated with the L (large) and P (phosphoprotein) proteins, which provide RNA polymerase activity during replication.

Embedded within the lipid membrane are spikes of F (fusion) protein trimers and G (attachment) protein tetramers. The function of the G protein (except in the case of MojV-G) is to attach the virus to the surface of a host cell via Ephrin B1, B2, or B3, a family of highly conserved mammalian proteins.{{cite journal |author1=Bonaparte, M |author2=Dimitrov, A |author3=Bossart, K |year=2005 |title=Ephrin-B2 ligand is a functional receptor for Hendra virus and Nipah virus |journal=Proceedings of the National Academy of Sciences |volume=102 |issue=30 |pages=10652–7 |doi=10.1073/pnas.0504887102 |pmid=15998730 |pmc=1169237 |bibcode=2005PNAS..10210652B |doi-access=free }}{{cite journal |vauthors=Negrete OA, Levroney EL, Aguilar HC |title=EphrinB2 is the entry receptor for Nipah virus, an emergent deadly paramyxovirus |journal=Nature |volume=436 |issue=7049 |pages=401–5 |year=2005 |pmid=16007075 |doi=10.1038/nature03838 |bibcode=2005Natur.436..401N |s2cid=4367038|doi-access=free }}{{Cite journal |last1=Bowden |first1=Thomas A. |last2=Crispin |first2=Max |last3=Jones |first3=E. Yvonne |last4=Stuart|first4=David I.|date=1 October 2010|title=Shared paramyxoviral glycoprotein architecture is adapted for diverse attachment strategies |journal=Biochemical Society Transactions |volume=38 |issue=5 |pages=1349–1355 |doi=10.1042/BST0381349 |pmc=3433257 |pmid=20863312}} The structure of the attachment glycoprotein has been determined by X-ray crystallography.{{Cite journal |last1=Bowden |first1=Thomas A. |last2=Crispin |first2=Max |last3=Harvey |first3=David J. |last4=Aricescu |first4=A. Radu |last5=Grimes |first5=Jonathan M. |last6=Jones |first6=E. Yvonne |last7=Stuart |first7=David I. |date=1 December 2008 |title=Crystal Structure and Carbohydrate Analysis of Nipah Virus Attachment Glycoprotein: a Template for Antiviral and Vaccine Design|journal=Journal of Virology |volume=82 |issue=23 |pages=11628–11636 |doi=10.1128/JVI.01344-08 |pmc=2583688 |pmid=18815311}} The F protein fuses the viral membrane with the host cell membrane, releasing the virion contents into the cell. It also causes infected cells to fuse with neighbouring cells to form large, multinucleated syncytia.

File:Journal.pone.0199534.g001.A.png

As all mononegaviral genomes, Hendra virus and Nipah virus genomes are non-segmented, single-stranded negative-sense RNA. Both genomes are 18.2 kb in length and contain six genes corresponding to six structural proteins.{{cite journal |vauthors=Wang L, Harcourt BH, Yu M |title=Molecular biology of Hendra and Nipah viruses |journal=Microbes and Infection |volume=3 |issue=4 |pages=279–87 |year=2001 |pmid=11334745 |doi=10.1016/S1286-4579(01)01381-8}}

In common with other members of the Paramyxoviridae family, the number of nucleotides in the henipavirus genome is a multiple of six, consistent with what is known as the 'rule of six'.{{Cite journal |last1=Halpin |first1=Kim |last2=Bankamp |first2=Bettina |last3=Harcourt |first3=Brian H. |last4=Bellini |first4=William J. |last5=Rota |first5=Paul A. |date=2004 |title=Nipah virus conforms to the rule of six in a minigenome replication assay |journal=Journal of General Virology |volume=85 |issue=3 |pages=701–707 |doi=10.1099/vir.0.19685-0 |pmid=14993656 |doi-access=free |issn=1465-2099}}{{cite journal |last1=Kolakofsky |first1=D |author2=Pelet, T |author3=Garcin, D |author4=Hausmann, S |author5=Curran, J |author6=Roux, L |title=Paramyxovirus RNA synthesis and the requirement for hexamer genome length: the rule of six revisited|journal=Journal of Virology|date=February 1998|volume=72|issue=2|pages=891–9|pmid=9444980|pmc=124558|doi=10.1128/JVI.72.2.891-899.1998 }} Deviation from the rule of six, through mutation or incomplete genome synthesis, leads to inefficient viral replication, probably due to structural constraints imposed by the binding between the RNA and the N protein.

Three additional protein products are produced from the henipavirus P gene: V, W, and C. The V and W proteins are generated through an unusual process called RNA editing. This specific process in henipaviruses involves the insertion of extra guanosine residues into the P gene mRNA prior to translation. The addition of a single guanosine results in production of V, and the addition of two guanosines residues produces W.{{Cite journal |last=Shaw |first=Megan L. |date=December 2009 |title=Henipaviruses Employ a Multifaceted Approach to Evade the Antiviral Interferon Response |journal=Viruses |language=en |volume=1 |issue=3 |pages=1190–1203 |doi=10.3390/v1031190 |issn=1999-4915 |pmc=3185527 |pmid=21994589 |doi-access=free }} The C protein is not produced through RNA editing but instead by leaky scanning of the host cell ribosome during translation of viral mRNA. P, V, and W possess an alternate open reading frame which results in production of C. P, V, W, and C are known to disrupt the host innate antiviral immune response through several different mechanisms.{{Cite journal |last1=Lawrence |first1=Philip |last2=Escudero-Pérez |first2=Beatriz |date=2022-04-29 |title=Henipavirus Immune Evasion and Pathogenesis Mechanisms: Lessons Learnt from Natural Infection and Animal Models |journal=Viruses |volume=14 |issue=5 |pages=936 |doi=10.3390/v14050936 |issn=1999-4915 |pmc=9146692 |pmid=35632678 |doi-access=free }} P, V, and W contain STAT1 binding domains, and act as interferon antagonists by sequestering STAT1 in the nucleus and cytoplasm.{{Cite journal |last1=Shaw |first1=Megan L. |last2=García-Sastre |first2=Adolfo |last3=Palese |first3=Peter |last4=Basler |first4=Christopher F. |date=June 2004 |title=Nipah virus V and W proteins have a common STAT1-binding domain yet inhibit STAT1 activation from the cytoplasmic and nuclear compartments, respectively |journal=Journal of Virology |volume=78 |issue=11 |pages=5633–5641 |doi=10.1128/JVI.78.11.5633-5641.2004 |issn=0022-538X |pmc=415790 |pmid=15140960}} The C protein controls the early pro-inflammatory response and is also known to promote the viral budding process via a ESCRT-dependent pathway.{{Cite journal |last1=Lo |first1=Michael K. |last2=Peeples |first2=Mark E. |last3=Bellini |first3=William J. |last4=Nichol |first4=Stuart T. |last5=Rota |first5=Paul A. |last6=Spiropoulou |first6=Christina F. |date=2012-10-19 |title=Distinct and Overlapping Roles of Nipah Virus P Gene Products in Modulating the Human Endothelial Cell Antiviral Response |journal=PLOS ONE |language=en |volume=7 |issue=10 |pages=e47790 |doi=10.1371/journal.pone.0047790 |issn=1932-6203 |pmc=3477106 |pmid=23094089 |bibcode=2012PLoSO...747790L |doi-access=free }}{{Cite journal |last1=Park |first1=Arnold |last2=Yun |first2=Tatyana |last3=Vigant |first3=Frederic |last4=Pernet |first4=Olivier |last5=Won |first5=Sohui T. |last6=Dawes |first6=Brian E. |last7=Bartkowski |first7=Wojciech |last8=Freiberg |first8=Alexander N. |last9=Lee |first9=Benhur |date=2016-05-20 |title=Nipah Virus C Protein Recruits Tsg101 to Promote the Efficient Release of Virus in an ESCRT-Dependent Pathway |journal=PLOS Pathogens |language=en |volume=12 |issue=5 |pages=e1005659 |doi=10.1371/journal.ppat.1005659 |pmid=27203423 |pmc=4874542 |issn=1553-7374 |doi-access=free }}

Cell receptor ephrin-B2, which is located on epithelial cells around smaller arteries, neurons, and smooth muscle cells, is targeted by the viral protein G.{{Cite journal |last1=Bonaparte |first1=Matthew I. |last2=Dimitrov |first2=Antony S. |last3=Bossart |first3=Katharine N. |last4=Crameri |first4=Gary |last5=Mungall |first5=Bruce A. |last6=Bishop |first6=Kimberly A. |last7=Choudhry |first7=Vidita |last8=Dimitrov |first8=Dimiter S. |last9=Wang |first9=Lin-Fa |last10=Eaton |first10=Bryan T. |last11=Broder |first11=Christopher C. |date=2005-07-05 |title=Ephrin-B2 ligand is a functional receptor for Hendra virus and Nipah virus |journal=Proceedings of the National Academy of Sciences |volume=102 |issue=30 |pages=10652–10657 |doi=10.1073/pnas.0504887102 |pmid=15998730 |pmc=1169237 |bibcode=2005PNAS..10210652B |issn=0027-8424|doi-access=free }} Once the protein G binds to ephrin-B2, the viral protein F facilitates fusion with the host cell membrane and releases viral RNA into the host cell cytoplasm.{{Cite journal |last=Zuckerman |first=Arie J. |date=1996-06-10 |title=Fields virology, 3rd edn. (two vol. set): Edited by B.N. Fields, D.M. Knipe, P.M. Howley, R.M. Chanock, J.L. Melnick, T.P. Monath, B. Roizman and S.E. Straus, Lippincott-Raven, Philadelphia, PA. 1996. 3216 pp. $339.50 (hc). ISBN 0 7817 0253 4 |journal=FEBS Letters |language=en |volume=388 |issue=1 |pages=88 |doi=10.1016/0014-5793(96)88179-8|doi-access=free |bibcode=1996FEBSL.388...88Z }} Upon entry, transcription of viral mRNA takes place using the viral RNA as a template. This process is started and stopped by the polymerase complex. Viral proteins are gathering in the cell as transcription occurs until the polymerase complex stops transcription and starts genome replication. Transcription of the viral RNA makes positive sense strands of RNA, which are then used as templates to make more negative sense viral RNA . Genome replication is halted before the viral particles can assemble to make a virion. Once the cell membrane is ready, new virions exit the host cell through budding.{{Citation |last1=Rota |first1=Paul A. |title=Molecular Virology of the Henipaviruses |date=2012 |work=Henipavirus |volume=359 |pages=41–58 |editor-last=Lee |editor-first=Benhur |place=Berlin, Heidelberg |publisher=Springer Berlin Heidelberg |doi=10.1007/82_2012_211 |isbn=978-3-642-29818-9 |last2=Lo |first2=Michael K. |pmid=22552699 |editor2-last=Rota |editor2-first=Paul A.}}

Henipaviruses have high mortality rates in mammalian hosts, both human and animal. Because of this, there is a need for immunization against HeV and NiV. The World Health Organization has classified henipaviral agents as R&D Blueprint Priority Pathogens, indicating that they pose a significant risk due to their epidemic potential.{{Cite web |title=Prioritizing diseases for research and development in emergency contexts |url=https://www.who.int/activities/prioritizing-diseases-for-research-and-development-in-emergency-contexts |access-date=2023-03-29 |website=www.who.int |language=en}} The broad species tropism of NiV and HeV have resulted in mortality in livestock species in addition to humans, and as a result veterinary vaccines are in various stages of development or licensure. EquiVac HeV, a veterinary vaccine for horses was licensed in Australia in 2012.{{Cite web |title=Equivac® HeV |url=https://www.zoetis.com.au/all-products/portal-site/equivac-hev.aspx |access-date=2023-03-29 |website=www.zoetis.com.au |language=en}}{{Cite journal |last1=Halpin |first1=Kim |last2=Graham |first2=Kerryne |last3=Durr |first3=Peter A. |date=2021-07-02 |title=Sero-Monitoring of Horses Demonstrates the Equivac® HeV Hendra Virus Vaccine to Be Highly Effective in Inducing Neutralising Antibody Titres |journal=Vaccines |volume=9 |issue=7 |pages=731 |doi=10.3390/vaccines9070731 |issn=2076-393X |pmc=8310234 |pmid=34358146 |doi-access=free }} A number of experimental vaccines designed for humans are in preclinical development, but none have yet been licensed. A soluble HeV attachment glycoprotein vaccine designed to protect against NiV completed a phase I clinical trial in November 2022, but results have not yet been published.{{Cite journal |last=Auro Vaccines LLC |date=2022-11-16 |others=PATH, Coalition for Epidemic Preparedness Innovations, Cincinnati Children's Hospital Medical Center (CCHMC) |title=A Phase 1 Randomized, Placebo-controlled, Observer-blind Trial to Assess the Safety and Immunogenicity of a Nipah Vaccine, HeV-sG-V (Hendra Virus Soluble Glycoprotein Vaccine), in Healthy Adults |website=ClinicalTrials.gov |url=https://clinicaltrials.gov/ct2/show/NCT04199169}}

The primary mechanism of protection against NiV and HeV induced by vaccination is thought to be neutralizing antibodies.{{Cite journal |last1=Amaya |first1=Moushimi |last2=Broder |first2=Christopher C. |date=2020-09-29 |title=Vaccines to Emerging Viruses: Nipah and Hendra |journal=Annual Review of Virology |language=en |volume=7 |issue=1 |pages=447–473 |doi=10.1146/annurev-virology-021920-113833 |issn=2327-056X |pmc=8782152 |pmid=32991264 |doi-access=free}} However, a number of preclinical vaccine studies in animal models of disease have identified that the cell-mediated immune response including CD8+ and CD4+ T-cells may play a role in protection.{{Cite journal |last1=Liew |first1=Yvonne Jing Mei |last2=Ibrahim |first2=Puteri Ainaa S. |last3=Ong |first3=Hui Ming |last4=Chong |first4=Chee Ning |last5=Tan |first5=Chong Tin |last6=Schee |first6=Jie Ping |last7=Gómez Román |first7=Raúl |last8=Cherian |first8=Neil George |last9=Wong |first9=Won Fen |last10=Chang |first10=Li-Yen |date=June 2022 |title=The Immunobiology of Nipah Virus |journal=Microorganisms |language=en |volume=10 |issue=6 |pages=1162 |doi=10.3390/microorganisms10061162 |issn=2076-2607 |pmc=9228579 |pmid=35744680 |doi-access=free }}

The emergence of henipaviruses parallels the emergence of other zoonotic viruses in recent decades. SARS coronavirus, Australian bat lyssavirus, Menangle virus, Marburg virus, COVID 19 and possibly Ebola viruses are also harboured by bats, and are capable of infecting a variety of other species. The emergence of each of these viruses has been linked to an increase in contact between bats and humans, sometimes involving an intermediate domestic animal host. The increased contact is driven both by human encroachment into the bats' territory (in the case of Nipah, specifically pigpens in said territory) and by movement of bats towards human populations due to changes in food distribution and loss of habitat.

There is evidence that habitat loss for flying foxes, both in South Asia and Australia (particularly along the east coast) as well as encroachment of human dwellings and agriculture into the remaining habitats, is creating greater overlap of human and flying fox distributions.{{Cite journal |last1=Breed |first1=Andrew C. |last2=Field |first2=Hume E. |last3=Epstein |first3=Jonathan H. |last4=Daszak |first4=Peter |date=August 2006 |title=Emerging henipaviruses and flying foxes - Conservation and management perspectives |journal=Biological Conservation |volume=131 |issue=2 |pages=211–220 |doi=10.1016/j.biocon.2006.04.007 |issn=0006-3207 |pmc=7096729 |pmid=32226079|bibcode=2006BCons.131..211B }}

The genus contains the following species, listed by scientific name and followed by their common names:{{cite web|title=Virus Taxonomy: 2024 Release|url=https://ictv.global/taxonomy|publisher=International Committee on Taxonomy of Viruses|access-date=14 March 2025}}

• Henipavirus angavokelyense, Angavokely virus
• Henipavirus cedarense, Cedar virus
• Henipavirus ghanaense, Ghanaian bat henipavirus, also called Kumasi virus
• Henipavirus hendraense, Hendra virus
• Henipavirus nipahense, Nipah virus

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• Animal viruses
• Paramyxovirus

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{{Commons category|Henipavirus}}

• [http://www.ictv.global/report/paramyxoviridae ICTV Report: Paramyxoviridae]
• [http://www.oie.int/en/animal-health-in-the-world/technical-disease-cards/ Disease card]
• [http://www.expasy.org/viralzone/all_by_species/85.html ViralZone: Henipavirus]
• [https://web.archive.org/web/20150801131243/http://henipavirus.net/ Henipavirus] – Henipavirus Ecology Research Group (HERG) INFO
• [http://www.viprbrc.org/brc/home.do?decorator=paramyxo Virus Pathogen Database and Analysis Resource (ViPR): Paramyxoviridae]

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Category:Animal virology

Category:Paramyxoviridae

Category:Virus genera

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