Henipavirus is a genus of the family Paramyxoviridae, order Mononegavirales containing two established species: Hendra virus and Nipah virus. The henipaviruses are naturally harboured by Pteropid fruit bats (flying foxes) and some microbat species. Henipavirus is characterised by a large genome, a wide host range, and their recent emergence as zoonotic pathogens capable of causing illness and death in domestic animals and humans.
In 2009, RNA sequences of three novel viruses in phylogenetic relationship to known Henipaviruses were detected in Eidolon helvum (the African Straw-coloured fruit bat) in Ghana. The finding of these novel putative Henipaviruses outside Australia and Asia indicates that the region of potential endemicity of Henipaviruses extends to Africa.
Henipaviruses
Virus classification Group: Group V ((-)ssRNA) Order: Mononegavirales Family: Paramyxoviridae
Genus: Henipavirus
Type species : Hendra virus
Species : Nipah virus
Virus structure
Henipaviruses are pleomorphic (variably shaped), ranging in size from 40 to 600 nm in diameter. 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 EFNB2, a highly conserved protein present in many mammals.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 negative-sense RNA. Both genomes are 18.2 kb in size and contain six genes corresponding to six structural proteins.
In common with other members of the Paramyxovirinae subfamily, the number of nucleotides in the henipavirus genome is a multiple of six, consistent with what is 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 specific process in henipaviruses involves the insertion of extra guanosine residues into the P gene mRNA prior to 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
Hendra virus (originally Equine morbillivirus) was discovered in September 1994 when it caused the deaths of thirteen horses, and a trainer at a training complex in Hendra, a suburb of Brisbane in Queensland, Australia.
The index case, a mare, was housed with 19 other horses after falling ill, and died two days later. Subsequently, all of the horses became ill, with 13 dying. The remaining 6 animals were subsequently euthanised as a way of preventing relapsing infection and possible further transmission. Both the trainer, Victory ('Vic') Rail, 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 Mr Rail died of respiratory and renal failure. The source of the 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 1,000 km north of Brisbane resulting in the deaths of two horses and their owner. The owner, Mark Preston, assisted in necropsies of the horses and within three weeks was admitted to hospital suffering from meningitis. Mr Preston 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.
Vaccine
A subunit vaccine that will neutralise Hendra virus is in development and is expected to be available in 2013. It is composed of a soluble version of the G surface antigen on Hendra virus and has been successful in ferret models. The trial vaccine may be available in 2012.
The vaccine is intended to be used in horses as stopping the virus at this point should protect both horses and humans.
Pathology
Flying foxes experimentally infected with the Hendra virus develop a viraemia then excrete the virus in their urine, faeces and saliva for approximately one week. Although they excrete live virus during this time there is no other indication of an illness. Symptoms of Hendra virus infection of humans may be respiratory, including hemorrhage and edema of the lungs, or encephalitic, resulting in meningitis. In horses, infection usually causes pulmonary oedema, congestion and / or neurological signs.
Ephrin B2 has been identified as the main receptor for the henipaviruses.
