Henipavirus 333398 225953865 2008-07-16T04:48:43Z 129.96.142.10 Outbreak sites {{Taxobox | color = violet | name = Henipaviruses | virus_group = V | ordo = ''[[Mononegavirales]]'' | familia = ''[[Paramyxoviridae]]'' | genus = '''''Henipavirus''''' | type_species = ''[[Hendra virus|Hendravirus]]'' | subdivision_ranks = [[Species]] | subdivision = ''[[Nipah virus|Nipahvirus]]'' }} '''Henipavirus''' is a [[genus]] of the [[Family (biology)|family]] ''[[Paramyxoviridae]]'', [[Order (biology)|order]] ''[[Mononegavirales]]'' containing two members, '''Hendravirus''' and '''Nipahvirus'''. The henipaviruses are naturally harboured by [[Pteropus|Pteropid]] [[fruit bat]]s (flying foxes) and are characterised by a large [[genome]], a wide host range and their recent emergence as [[zoonosis|zoonotic]] pathogens capable of causing illness and death in [[domestic animal]]s and [[human]]s.<ref name=sobrino5>{{cite book |chapterurl=http://www.horizonpress.com/avir|author=Sawatsky et al|year=2008|chapter=Hendra and Nipah Virus|title=Animal Viruses: Molecular Biology|publisher=Caister Academic Press|id=[http://www.horizonpress.com/avir ISBN 978-1-904455-22-6]}}</ref> ==Virus structure== [[Image:Henipavirus structure.png|thumb|350px|right|Structure of henipaviruses]] [[Image:Henipavirus genome.png|frame|right|The henipavirus genome (3’ to 5’ orientation) and products of the P gene]] Henipaviruses are '''''pleomorphic''''' (variably shaped), ranging in size from 40 to 600 nm in diameter.<ref name=hyatt> Hyatt''et al''. Ultrastructure of Hendra virus and Nipah virus within cultured cells and host animals. ''Microbes and Infection'' 2001; '''3''': 297&ndash;306. PMID 11334747</ref> 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 is to attach the virus to the surface of a host cell via [[ephrin B2]], a highly conserved protein present in many mammals.<ref name="bonaparte">{{cite journal |author=Bonaparte, M; Dimitrov, A; Bossart, K; ''et al.'' |year=2005 |month= |title=Ephrin-B2 ligand is a functional receptor for Hendra virus and Nipah virus |journal=[[Proceedings of the National Academy of Sciences|PNAS]] |volume=102 |issue=30 |pages=10652&ndash;10657 |doi=10.1073/pnas.0504887102 |url= |accessdate= |quote=|pmid=15998730 }}</ref><ref name="negrete">{{cite journal |last=Negrete |first=Oscar A. |authorlink= |coauthors=''et al.'' |year=2005 |month= |title=EphrinB2 is the entry receptor for Nipah virus, an emergent deadly paramyxovirus |journal=[[Nature (journal)|Nature]] |volume=436 |issue= |pages=401&ndash;405 |doi=10.1038/nature03838 |url= |accessdate= |quote= }}</ref> 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]]. ==Genome structure== As with all viruses in the ''Mononegavirales'' order, the Hendra virus and Nipah virus genomes are non-segmented, single-stranded [[sense (molecular biology)|negative-sense]] RNA. Both genomes are 18.2 kb in size and contain six [[gene]]s corresponding to six structural proteins.<ref name=wang>Wang L, Harcourt BH, Yu M, ''et al''. Molecular biology of Hendra and Nipah viruses. ''Microbes and Infection'' 2001; '''3''': 279&ndash;287. PMID 11334745</ref> In common with other members of the ''Paramyxovirinae'' subfamily, the number of [[nucleotide]]s in the henipavirus genome is a multiple of six, known as the 'rule of six'. 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. Henipaviruses employ an unusual process called [[RNA editing]] to generate multiple proteins from a single gene. The process involves the insertion of extra [[guanosine]] residues into the P gene [[mRNA]] prior to [[translation (genetics)|translation]]. The number of residues added determines whether the P, V or W proteins are synthesised. The functions of the V and W proteins are unknown, but they may be involved in disrupting host antiviral mechanisms. ==Hendra virus== ===Emergence=== Hendra virus (originally ''Equine [[morbillivirus]]'') was discovered in September [[1994]] when it caused the deaths of fourteen [[horse]]s, and a trainer at a training complex in [[Hendra, Queensland|Hendra]], a suburb of [[Brisbane]] in [[Queensland]], [[Australia]].<ref>Selvey, LA, Wells, RM, McCormack, JG, ''et al''. Infection of humans and horses by a newly described morbillivirus. ''Medical Journal of Australia'' 1995; '''162(12)''':642&ndash;645. PMID 7603375</ref> The index case, a mare, was housed with 23 other horses after falling ill and died two days later. Subsequently, 19 of the remaining horses succumbed with 13 dying. Both the trainer and a stable hand were involved in nursing the index case and both fell ill within one week of the horse’s death with an influenza-like illness. The stable hand recovered while the trainer died of respiratory and renal failure. The source of virus was most likely frothy nasal discharge from the index case. A second [[outbreak]] occurred in August 1994 (chronologically preceding the first outbreak) in [[Mackay, Queensland|Mackay]] 1000km north of Brisbane resulting in the deaths of two horses and their owner.<ref name=field>Field H, Young P, Yob JM, ''et al''. The natural history of Hendra and Nipah viruses. ''Microbes and Infection'' 2001; '''3''':307&ndash;314. PMID 11334748</ref> The owner assisted in [[autopsy|autopsies]] of the horses and within three weeks was admitted to hospital suffering from [[meningitis]]. He recovered, but 14 months later developed neurologic signs and died. This outbreak was diagnosed retrospectively by the presence of Hendra virus in the brain of the patient. A survey of wildlife in the outbreak areas was conducted and identified pteropid fruit bats as the most likely source of Hendra virus with a [[seroprevalence]] of 47%. All of the other 46 species sampled were negative. Virus isolations from the reproductive tract and urine of wild bats indicated that transmission to horses may have occurred via exposure to bat urine or birthing fluids.<ref name=halpin>Halpin K, Young PL, Field HE, Mackenzie JS. Isolation of Hendra virus from pteropid bats: a natural reservoir of Hendra virus. ''Journal of General Virology'' 2000; '''81''':1927&ndash;1932. PMID 10900029 [http://vir.sgmjournals.org/cgi/content/full/81/8/1927 Available from http://vir.sgmjournals.org/cgi/content/full/81/8/1927]</ref>. ===Outbreaks=== A total of eight outbreaks of Hendra virus have occurred since 1994, all involving infection of horses. Four of these outbreaks have spread to humans as a result of direct contact with infected horses. * August 1994, Mackay, Queensland: Death of two horses and one person.<ref name=field>Field H, Young P, Yob JM, ''et al''. The natural history of Hendra and Nipah viruses. ''Microbes and Infection'' 2001; '''3''':307&ndash;314. PMID 11334748</ref> * September 1994, Brisbane, Queensland: 14 horses died from a total of 20 infected. Two people infected with one death.<ref>Selvey, LA, Wells, RM, McCormack, JG, ''et al''. Infection of humans and horses by a newly described morbillivirus. ''Medical Journal of Australia'' 1995; '''162(12)''':642&ndash;645. PMID 7603375</ref> * January 1999, [[Cairns]], Queensland: Death of one horse.<ref>Field, HE, Barrat, PC, Hughes, RJ, ''et al''. A fatal case of Hendra virus infection in a horse in north Queensland: clinical and epidemiological features. ''Australian Veterinary Journal'' 2000; '''78(4)''':279&ndash;280. PMID 10840578</ref> * October 2004, Cairns, Queensland: Death of one horse. A vet involved in autopsy of the horse was infected with Hendra virus and suffered a mild illness.<ref>Hanna, JN, McBride, WJ, Brookes, DL, ''et al''. Hendra virus infection in a veterinarian. ''Medical Journal of Australia'' 2006; '''185(10)''':562&ndash;564. PMID 17115969</ref> * December 2004, [[Townsville]], Queensland: Death of one horse.<ref>Hanna, JN, McBride, WJ, Brookes, DL, ''et al''. Hendra virus infection in a veterinarian. ''Medical Journal of Australia'' 2006; '''185(10)''':562&ndash;564. PMID 17115969</ref> * June 2006, [[Sunshine Coast]], Queensland: Death of one horse.<ref>Hanna, JN, McBride, WJ, Brookes, DL, ''et al''. Hendra virus infection in a veterinarian. ''Medical Journal of Australia'' 2006; '''185(10)''':562&ndash;564. PMID 17115969</ref> * July 2008, Brisbane, Queensland: Infection of three horses with one death. A veterinary worker from the affected property tested positive to antibodies to Hendra virus. * July 2008, [[Cannonvale]], Queensland: Death of one horse. The distribution of black and spectacled flying foxes covers the outbreak sites, and the timing of incidents indicates a seasonal pattern of outbreaks possibly related to the seasonality of fruit bat birthing. As there is no evidence of transmission to humans directly from bats, it is thought that human infection only occurs via an intermediate host. ===Pathology=== Flying foxes are unaffected by Hendra virus infection. Symptoms of Hendra virus infection of humans may be respiratory, including [[haemorrhage]] and [[pulmonary oedema|oedema]] of the lungs, or [[encephalitis|encephalitic]] resulting in [[meningitis]]. In horses, infection usually causes pulmonary oedema and congestion. ==Nipah virus== ===Emergence=== [[Image:Pteropus vampyrus1.jpg|thumb|right|''Pteropus vampyrus'' (Malayan flying fox), one of the natural reservoirs of Nipah virus]] Nipah virus was identified in 1999 when it caused an outbreak of neurological and respiratory disease on pig farms in peninsular [[Malaysia]], resulting in 105 human deaths and the culling of one million pigs.<ref name=field>Field H, Young P, Yob JM, ''et al''. The natural history of Hendra and Nipah viruses. ''Microbes and Infection'' 2001; '''3''':307&ndash;314. PMID 11334748</ref> In [[Singapore]], 11 cases including one death occurred in abattoir workers exposed to pigs imported from the affected Malaysian farms. The Nipah virus has been classified by the CDC as a Category C agent (http://www.bt.cdc.gov/agent/agentlist-category.asp). Symptoms of infection from the Malaysian outbreak were primarily encephalitic in humans and respiratory in pigs. Later outbreaks have caused respiratory illness in humans, increasing the likelihood of human-to-human transmission and indicating the existence of more dangerous strains of the virus. Based on seroprevalence data and virus isolations, the primary reservoir for Nipah virus was identified as Pteropid fruit bats including ''Pteropus vampyrus'' (Malayan flying fox) and ''Pteropus hypomelanus'' (Island flying fox), both of which occur in Malaysia. The transmission of Nipah virus from flying foxes to pigs is thought to be due to an increasing overlap between bat habitats and piggeries in peninsular Malaysia. At the index farm, fruit orchards were in close proximity to the piggery, allowing the spillage of urine, faeces and partially eaten fruit onto the pigs.<ref name=chua>Chua KB, Chua BH, Wang CW. Anthropogenic deforestation, El Nino and the emergence of Nipah virus in Malaysia. ''Malaysian J Pathol'' 2002; '''24''': 15&ndash;21. PMID 16329551</ref> Retrospective studies demonstrate that viral spillover into pigs may have been occurring in Malaysia since 1996 without detection.<ref name=field>Field H, Young P, Yob JM, ''et al''. The natural history of Hendra and Nipah viruses. ''Microbes and Infection'' 2001; '''3''':307&ndash;314. PMID 11334748</ref> During 1998, viral spread was aided by the transfer of infected pigs to other farms where new outbreaks occurred. ===Outbreaks=== Eight more outbreaks of Nipah virus have occurred since [[1998]], all within [[Bangladesh]] and neighbouring parts of [[India]]. The outbreak sites lie within the range of Pteropus species (''Pteropus giganteus''). As with Hendra virus, the timing of the outbreaks indicates a seasonal effect. [[Image:Flying fox distribution.png|thumb|350px|right|Locations of henipavirus outbreaks (red stars&ndash;Hendra virus; blue stars&ndash;Nipah virus) and distribution of henipavirus flying fox reservoirs (red shading&ndash;Hendra virus ; blue shading&ndash;Nipah virus)]] * 2001 January 31 – February 23, [[Siliguri]], India: 66 cases with a 74% mortality rate.<ref name=chadha>Chadha MS, James AC, Lowe L ''et al''. Nipah virus-associated encephalitis outbreak, Siliguri, India. ''Emerging Infectious Diseases'' 2006; '''12''':235&ndash;240. PMID 16494748</ref> 75% of patients were either hospital staff or had visited one of the other patients in hospital, indicating person-to-person transmission. * 2001 April – May, [[Meherpur]] district, Bangladesh: 13 cases with nine fatalities (69% mortality).<ref name=hsu>Hsu VP, Hossain MJ, Parashar UD, ''et al''. Nipah virus encephalitis reemergence, Bangladesh. ''Emerging Infectious Disease'' 2004; '''10''': 2082&ndash;2087. PMID 15663842. [http://www.cdc.gov/ncidod/EID/vol10no12/04-0701.htm Available from http://www.cdc.gov/ncidod/EID/vol10no12/04-0701.htm]</ref> * 2003 January, [[Naogaon]] district, Bangladesh: 12 cases with eight fatalities (67% mortality).<ref name=hsu>Hsu VP, Hossain MJ, Parashar UD, ''et al''. Nipah virus encephalitis reemergence, Bangladesh. ''Emerging Infectious Disease'' 2004; '''10''': 2082&ndash;2087. PMID 15663842. [http://www.cdc.gov/ncidod/EID/vol10no12/04-0701.htm Available from http://www.cdc.gov/ncidod/EID/vol10no12/04-0701.htm]</ref> * 2004 January – February, [[Manikganj]] and [[Rajbari]] provinces, Bangladesh: 42 cases with 14 fatalities (33% mortality). * 2004 [[19 February]] – [[16 April]], [[Faridpur]] district, Bangladesh: 36 cases with 27 fatalities (75% mortality). Epidemiological evidence strongly suggests that this outbreak involved person-to-person transmission of Nipah virus, which had not previously been confirmed.<ref>[http://www.icddrb.org/pub/publication.jsp?pubID=5144&classificationID=0&typeClassificationID=0 ICDDR,B. (2004). Nipah encephalitis outbreak over wide area of Western Bangladesh, 2004. ''Health and Science Bulletin''. '''2(1)''':7&ndash;11.]</ref> 92% of cases involved close contact with at least one other person infected with Nipah virus. Two cases involved a single short exposure to an ill patient, including a rickshaw driver who transported a patient to hospital. In addition, at least six cases involved acute respiratory distress syndrome which has not been reported previously for Nipah virus illness in humans. This symptom is likely to have assisted human-to-human transmission through large droplet dispersal. * 2005 January, [[Tangail]] district, Bangladesh: 12 cases with 11 fatalities (92% mortality). The virus was probably contracted from drinking date palm juice contaminated by fruit bat droppings or saliva.<ref>[http://www.icddrb.org/pub/publication.jsp?classificationID=56&pubID=6590 ICDDR,B. (2005). Nipah virus outbreak from date palm juice. ''Health and Science Bulletin''. '''3(4)''':1&ndash;5.]</ref> * 2007 February – May, [[Nadia|Nadia District]], India: up to 50 suspected cases with 3-5 fatalities. The outbreak site borders the Bangladesh district of [[Kushtia]] where eight cases of Nipah virus encephalitis with five fatalities occurred during March and April 2007. This was preceded by an outbreak in [[Thakurgaon]] during January and February affecting seven people with three deaths.<ref>[http://www.icddrb.org/pub/publication.jsp?pubID=9038&classificationID=0&typeClassificationID=0. ICDDR,B. (2007). Person-to-person transmission of Nipah infection in Bangladesh, 2007. ''Health and Science Bulletin''. '''5(4)''':1&ndash;6.]</ref> All three outbreaks showed evidence of person-to-person transmission. * 2008 February - March, Manikganj and Rajbari provinces, Bangladesh: Nine cases with eight fatalities.<ref>[http://www.icddrb.org/pub/publication.jsp?pubID=9038&classificationID=0&typeClassificationID=0. ICDDR,B. (2008). Outbreaks of Nipah virus in Rajbari and Manikgonj, February 2008. ''Health and Science Bulletin''. '''6(1)''':12&ndash;13.]</ref> Eleven isolated cases of Nipah virus encephalitis have also been documented in Bangladesh since 2001. Nipah virus has been isolated from Lyle's flying fox (''Pteropus lylei'') in [[Cambodia]]<ref name=reynes> Reynes JM, Counor D, Ong S, ''et al''. Nipah virus in Lyle’s flying foxes, Cambodia. ''Emerging Infectious Diseases'' 2005; '''11''':1042&ndash;7. PMID 16022778. [http://www.cdc.gov/ncidod/EID/vol11no07/04-1350.htm Available from http://www.cdc.gov/ncidod/EID/vol11no07/04-1350.htm]</ref> and viral RNA found in urine and saliva from ''P. lylei'' and Horsfield's roundleaf bat (''Hipposideros larvartus'') in [[Thailand]].<ref name=Wacharapluesadee>Wacharapluesadee S, Lumlertdacha B, Boongird K, ''et al''. Bat Nipah virus, Thailand. ''Emerging Infectious Diseases'' 2005; '''11''': 1949-51. PMID 16485487. [http://www.cdc.gov/ncidod/EID/vol11no12/05-0613.htm Available from http://www.cdc.gov/ncidod/EID/vol11no12/05-0613.htm] </ref> Infective virus has also been isolated from environmental samples of bat urine and partially-eaten fruit in Malaysia.<ref name="Chua KB">Chua KB, Koh CL, Hooi PS, Wee KF, Khong JH, Chua BH, Chan YP, Lim ME, Lam SK. Isolation of Nipah virus from Malaysian Island flying-foxes. Microbes and Infection. 2002 Feb;4(2):145-51. PMID: 11880045 </ref> [[antibody|Antibodies]] to henipaviruses have also been found in fruit bats (''Pteropus rufus, Eidolon dupreanum'') in [[Madagascar]] indicating a wide geographic distribution of the viruses.<ref>Iehle, C, Razafitrimo, G, Razainirina, J, ''et al''. Henipavirus and Tioman virus in Pteropodid bats, Madagascar. ''Emerging Infectious Diseases'' 2007; '''13(1)'''. [http://www.cdc.gov/EID/13/1/06-0791.htm Available from http://www.cdc.gov/EID/13/1/06-0791.htm] </ref> No infection of humans or other species have been observed in Cambodia, Thailand or Madagascar. ===Pathology=== In humans, the infection presents as fever, headache and drowsiness. Cough, abdominal pain, nausea, vomiting, weakness, problems with swallowing and blurred vision are relatively common. About a quarter of the patients have seizures and about 60% become comatose and might need mechanical ventilation. In patients with severe disease, their conscious state may deteriorate and they may develop severe hypertension, fast heart rate, and very high temperature. Nipah virus is also known to cause relapse encephalitis. In the initial Malaysian outbreak, a patient presented with relapse encephalitis some 53 months after his initial infection. There is no definitive treatment for Nipah encephalitis, apart from supportive measures, such as mechanical ventilation and prevention of secondary infection. [[Ribavirin]], an antiviral drug, was tested in the Malaysian outbreak and the results were encouraging, though further studies are still needed. In animals, especially in pigs, the virus causes porcine respiratory and neurologic syndrome also known as barking pig syndrome or one mile cough. ==Causes of Emergence== The emergence of henipaviruses parallels the emergence of other zoonotic viruses in recent decades. [[SARS coronavirus]], [[Australian bat lyssavirus]], [[Menangle virus]] and probably [[Ebola virus]] and [[Marburg virus]] are also harbored 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 of 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, creating greater overlap of human and flying fox distributions. ==See also== *[[Animal virology|Animal viruses]] *[[Paramyxovirus]] ==References== {{reflist|2}} ==External links== *[http://www.csiro.au/csiro/content/standard/ps1o5,,.html Hendra virus] [[CSIRO]] FAQ *[http://www.csiro.au/csiro/content/standard/ps1so,,.html Nipah virus] [[CSIRO]] FAQ *[http://www.henipavirus.net Henipavirus] [[Henipavirus Ecology Research Group (HERG)]] INFO *[http://www.horizonpress.com/gateway/animal-viruses.html Animal viruses] {{Viral diseases}} [[Category:Mononegavirales]] [[Category:Viral diseases]] [[Category:Zoonoses]] [[Category:Animal virology]] [[Category:Microbiology]] [[de:Henipavirus]] [[fr:Henipavirus]] [[pl:Wirus Nipah]]