Henipavirus | |
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Colored transmission electron micrograph of a Hendra henipavirus virion (ca. 300 nm length) | |
Virus classification | |
(unranked): | Virus |
Realm: | Riboviria |
Kingdom: | Orthornavirae |
Phylum: | Negarnaviricota |
Class: | Monjiviricetes |
Order: | Mononegavirales |
Family: | Paramyxoviridae |
Subfamily: | Orthoparamyxovirinae |
Genus: | Henipavirus |
Species | |
Henipavirus is a genus of negative-strand RNA viruses in the family Paramyxoviridae , order Mononegavirales containing six established species, [1] [2] and numerous others still under study. [3] Henipaviruses are naturally harboured by several species of small mammals, notably pteropid fruit bats (flying foxes), microbats of several species, [4] and shrews. [5] [6] Henipaviruses are characterised by long genomes and a wide host range. Their recent emergence as zoonotic pathogens capable of causing illness and death in domestic animals and humans is a cause of concern. [7] [8]
In 2009, RNA sequences of three novel viruses in phylogenetic relationship to known henipaviruses were detected in African straw-colored fruit bats ( Eidolon helvum ) in Ghana. The finding of these novel henipaviruses outside Australia and Asia indicates that the region of potential endemicity of henipaviruses may be worldwide. [9] These African henipaviruses are slowly being characterised. [10]
Nipah and Hendra henipaviruses are both considered category C (USDA-HHS overlap) select agents. [11]
Henipavirions are pleomorphic (variably shaped), ranging in size from 40 to 600 nm in diameter. [12] 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. [13] [14] [15] The structure of the attachment glycoprotein has been determined by X-ray crystallography. [16] 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.
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. [17]
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'. [18] [19] 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. [20] 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. [21] P, V, and W contain STAT1 binding domains, and act as interferon antagonists by sequestering STAT1 in the nucleus and cytoplasm. [22] The C protein controls the early pro-inflammatory response and is also known to promote the viral budding process via a ESCRT-dependent pathway. [23] [24]
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. [25] 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. [26] 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. [27]
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. [28] 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. [29] [30] 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. [31]
The primary mechanism of protection against NiV and HeV induced by vaccination is thought to be neutralizing antibodies. [32] 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. [33]
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. [34]
Genus | Species | Virus (Abbreviation) |
Henipavirus | Cedar henipavirus | Cedar virus (CedV) |
Ghanaian bat henipavirus | Kumasi virus (KV) | |
Hendra henipavirus | Hendra virus (HeV) | |
Mojiang henipavirus | Mòjiāng virus (MojV) [3] | |
Nipah henipavirus | Nipah virus (NiV) | |
Langya henipavirus | Langya virus (LayV) [6] [36] |
Paramyxoviridae is a family of negative-strand RNA viruses in the order Mononegavirales. Vertebrates serve as natural hosts. Diseases associated with this family include measles, mumps, and respiratory tract infections. The family has four subfamilies, 17 genera, three of which are unassigned to a subfamily, and 78 species.
Mononegavirales is an order of negative-strand RNA viruses which have nonsegmented genomes. Some members that cause human disease in this order include Ebola virus, human respiratory syncytial virus, measles virus, mumps virus, Nipah virus, and rabies virus. Important pathogens of nonhuman animals and plants are also in the group. The order includes eleven virus families: Artoviridae, Bornaviridae, Filoviridae, Lispiviridae, Mymonaviridae, Nyamiviridae, Paramyxoviridae, Pneumoviridae, Rhabdoviridae, Sunviridae, and Xinmoviridae.
Human metapneumovirus is a negative-sense single-stranded RNA virus of the family Pneumoviridae and is closely related to the Avian metapneumovirus (AMPV) subgroup C. It was isolated for the first time in 2001 in the Netherlands by using the RAP-PCR technique for identification of unknown viruses growing in cultured cells. As of 2016, it was the second most common cause of acute respiratory tract illness in otherwise-healthy children under the age of 5 in a large US outpatient clinic.
The mumps virus (MuV) is the virus that causes mumps. MuV contains a single-stranded, negative-sense genome made of ribonucleic acid (RNA). Its genome is about 15,000 nucleotides in length and contains seven genes that encode nine proteins. The genome is encased by a capsid that is in turn surrounded by a viral envelope. MuV particles, called virions, are pleomorphic in shape and vary in size from 100 to 600 nanometers in diameter. One serotype and twelve genotypes that vary in their geographic distribution are recognized. Humans are the only natural host of the mumps virus.
Measles morbillivirus(MeV), also called measles virus (MV), is a single-stranded, negative-sense, enveloped, non-segmented RNA virus of the genus Morbillivirus within the family Paramyxoviridae. It is the cause of measles. Humans are the natural hosts of the virus; no animal reservoirs are known to exist.
Rabies virus, scientific name Rabies lyssavirus, is a neurotropic virus that causes rabies in animals, including humans. Rabies transmission can occur through the saliva of animals and less commonly through contact with human saliva. Rabies lyssavirus, like many rhabdoviruses, has an extremely wide host range. In the wild it has been found infecting many mammalian species, while in the laboratory it has been found that birds can be infected, as well as cell cultures from mammals, birds, reptiles and insects. Rabies is reported in more than 150 countries and on all continents except Antarctica. The main burden of disease is reported in Asia and Africa, but some cases have been reported also in Europe in the past 10 years, especially in returning travellers.
Nipah virus is a bat-borne, zoonotic virus that causes Nipah virus infection in humans and other animals, a disease with a very high mortality rate (40-75%). Numerous disease outbreaks caused by Nipah virus have occurred in South East Africa and Southeast Asia. Nipah virus belongs to the genus Henipavirus along with the Hendra virus, which has also caused disease outbreaks.
Pestivirus is a genus of viruses, in the family Flaviviridae. Viruses in the genus Pestivirus infect mammals, including members of the family Bovidae and the family Suidae. There are 11 species in this genus. Diseases associated with this genus include: hemorrhagic syndromes, abortion, and fatal mucosal disease.
A viral envelope is the outermost layer of many types of viruses. It protects the genetic material in their life cycle when traveling between host cells. Not all viruses have envelopes. A viral envelope protein or E protein is a protein in the envelope, which may be acquired by the capsid from an infected host cell.
Murine respirovirus, formerly Sendai virus (SeV) and previously also known as murine parainfluenza virus type 1 or hemagglutinating virus of Japan (HVJ), is an enveloped, 150-200 nm–diameter, negative sense, single-stranded RNA virus of the family Paramyxoviridae. It typically infects rodents and it is not pathogenic for humans or domestic animals.
Pseudotyping is the process of producing viruses or viral vectors in combination with foreign viral envelope proteins. The result is a pseudotyped virus particle, also called a pseudovirus. With this method, the foreign viral envelope proteins can be used to alter host tropism or increase or decrease the stability of the virus particles. Pseudotyped particles do not carry the genetic material to produce additional viral envelope proteins, so the phenotypic changes cannot be passed on to progeny viral particles. In some cases, the inability to produce viral envelope proteins renders the pseudovirus replication incompetent. In this way, the properties of dangerous viruses can be studied in a lower risk setting.
Cedar virus, officially Cedar henipavirus, is a henipavirus known to be harboured by Pteropus spp. Infectious virus was isolated from the urine of a mixed Pteropus alecto and P. poliocephalus in Queensland, Australia in 2009. Unlike the Nipah and Hendra virus, Cedar virus infection does not lead to obvious disease in vivo. Infected animals mounted effective immune responses and seroconverted in challenge studies.
Aquaparamyxovirus is a genus of viruses in the family Paramyxoviridae, order Mononegavirales. The genus includes two species. Fish serve as the natural hosts for AsaPV, in which the virus may cause proliferative gill inflammation.
Ferlavirus, also referred to as Ophidian paramyxovirus, is a genus of viruses in the family Paramyxoviridae, order Mononegavirales. Reptiles serve as natural hosts. There is currently only one species in this genus to accommodate a single virus, Fer-de-Lance virus (FDLV).
Pneumoviridae is a family of negative-strand RNA viruses in the order Mononegavirales. Humans, cattle, and rodents serve as natural hosts. Respiratory tract infections are associated with member viruses such as human respiratory syncytial virus. There are five species in the family which are divided between the genera Metapneumovirus and Orthopneumovirus. The family used to be considered as a sub-family of Paramyxoviridae, but has been reclassified as of 2016.
Avian metaavulavirus 2, formerly Avian paramyxovirus 2, is a species of virus belonging to the family Paramyxoviridae and genus Metaavulavirus. The virus is a negative strand RNA virus containing a monopartite genome. Avian metaavulavirus 2 is one of nine species belonging to the genus Metaavulavirus. The most common serotype of Avulavirinae is serotype 1, the cause of Newcastle disease (ND). Avian metaavulavirus 2 has been known to cause disease, specifically mild respiratory infections in domestic poultry, including turkeys and chickens, and has many economic effects on egg production and poultry industries. The virus was first isolated from a strain in Yucaipa, California in 1956. Since then, other isolates of the virus have been isolated worldwide.
A Nipah virus infection is a viral infection caused by the Nipah virus. Symptoms from infection vary from none to fever, cough, headache, shortness of breath, and confusion. This may worsen into a coma over a day or two, and 50 to 75% of those infected die. Complications can include inflammation of the brain and seizures following recovery.
Bat mumps orthorubulavirus, formerly Bat mumps rubulavirus (BMV), is a member of genus Orthorubulavirus, family Paramyxoviridae, and order Mononegavirales. Paramyxoviridae viruses were first isolated from bats using heminested PCR with degenerate primers. This process was then followed by Sanger sequencing. A specific location of this virus is not known because it was isolated from bats worldwide. Although multiple paramyxoviridae viruses have been isolated worldwide, BMV specifically has not been isolated thus far. However, BMV was detected in African fruit bats, but no infectious form has been isolated to date. It is known that BMV is transmitted through saliva in the respiratory system of bats. While the virus was considered its own species for a few years, phylogenetic analysis has since shown that it is a member of Mumps orthorubulavirus.
Ghanaian bat henipavirus (also known Kumasi virus belongs to the genus Henipavirus in the family Paramyxoviridae. Human infections are caused by zoonotic events where the virus crosses over from another animal species. Therefore, humans are not the innate host for this virus family but instead become infected by peripheral viral reservoirs such as bats and other carriers of the virus. When these virus are spread to humans through zoonotic events they have been found to be one of the most deadly viruses with the capability to infect humans, with mortality rates between 50 and 100%. Therefore, these viruses have been classified as a biosafety level four virus with regards to its pathogenesis when it infects humans.
Mòjiāng virus(MojV), officially Mojiang henipavirus, is a virus in the family Paramyxoviridae. Based on phylogenetics, Mòjiāng virus is placed in the genus Henipavirus or described as a henipa-like virus. Antibodies raised against Mòjiāng virus glycoproteins are serologically distinct from other henipaviruses (among which higher cross-reactivity is observed).