Nipah virus

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Nipah virus
Nipah virus from an infected VERO cell.jpg
False-color electron micrograph showing a Nipah virus particle (purple) by an infected Vero cell (brown)
Virus classification OOjs UI icon edit-ltr.svg
(unranked): Virus
Realm: Riboviria
Kingdom: Orthornavirae
Phylum: Negarnaviricota
Class: Monjiviricetes
Order: Mononegavirales
Family: Paramyxoviridae
Genus: Henipavirus
Species:
Nipah virus

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. [1]

Contents

Virology

Like other henipaviruses, the Nipah virus genome is a single (non-segmented) negative-sense, single-stranded RNA of over 18 kb, which is substantially longer than that of other paramyxoviruses. [2] [3] The enveloped virus particles are variable in shape, and can be filamentous or spherical; they contain a helical nucleocapsid. [2] Six structural proteins are generated: N (nucleocapsid), P (phosphoprotein), M (matrix), F (fusion), G (glycoprotein) and L (RNA polymerase). The P open reading frame also encodes three nonstructural proteins, C, V and W.

The Nipah virus structural model, constructed at an atomic resolution, depicts a particle with a diameter of 90 nm, adorned with spikes. This model affords a glimpse into the virus's interior. The Nipah virus is known for its high mortality rate and is viewed as a potential candidate for the next pandemic. The construction of this model utilized components from the UCSF Chimera database, sourced from the Protein Data Bank (pdb). Nipah 12142023 1 ps.tif
The Nipah virus structural model, constructed at an atomic resolution, depicts a particle with a diameter of 90 nm, adorned with spikes. This model affords a glimpse into the virus's interior. The Nipah virus is known for its high mortality rate and is viewed as a potential candidate for the next pandemic. The construction of this model utilized components from the UCSF Chimera database, sourced from the Protein Data Bank (pdb).

There are two envelope glycoproteins. The G glycoprotein ectodomain assembles as a homotetramer to form the viral anti-receptor or attachment protein, which binds to the receptor on the host cell. Each strand in the ectodomain consists of four distinct regions: at the N-terminal and connecting to the viral surface is the helical stalk, followed by the beta-sandwich neck domain, the linker region and finally, at the C-terminal, four heads which contain host cell receptor binding domains. [4] Each head consists of a beta-propeller structure with six blades. There are three unique folding patterns of the heads, resulting in a 2-up/2-down configuration where two heads are positioned distal to the virus and two heads are proximal. Due to the folding patterns and subsequent arrangement of the heads, only one of the four heads is positioned with its binding site accessible to associate with the host B2/B3 receptor. [4] The G protein head domain is also highly antigenic, inducing head-specific antibodies in primate models. As such, it is a prime target for vaccine development as well as antibody therapy. One head-specific antibody, m102.4, has been used in compassionate use cases and has completed Phase 1 clinical trials. [5] The F glycoprotein forms a trimer, which mediates membrane fusion. [2] [3]

Tropism

Ephrins B2 and B3 have been identified as the main receptors for Nipah virus. [2] [3] [6] Ephrin sub-types have a complex distribution of expression throughout the body, where the B3 is noted to have particularly high expression in some forebrain sub-regions. [7]

Geographic distribution

Pteropus vampyrus (large flying fox), one of the natural reservoirs of Nipah virus Pteropus vampyrus2.jpg
Pteropus vampyrus (large flying fox), one of the natural reservoirs of Nipah virus

Nipah virus has been isolated from Lyle's flying fox ( Pteropus lylei ) in Cambodia [8] and viral RNA found in urine and saliva from P. lylei and Horsfield's roundleaf bat ( Hipposideros larvatus ) in Thailand. [9] Ineffective forms of the virus has also been isolated from environmental samples of bat urine and partially eaten fruit in Malaysia. [10] Antibodies to henipaviruses have also been found in fruit bats in Madagascar ( Pteropus rufus, Eidolon dupreanum ) [11] and Ghana ( Eidolon helvum ) [12] indicating a wide geographic distribution of the viruses. No infection of humans or other species have been observed in Cambodia, Thailand or Africa as of May 2018. In September 2023, India reported at least five infections and two deaths. [13]

Symptoms

These symptoms can be followed by more serious conditions including:

History

Emergence

The first cases of Nipah virus infection were identified in 1998, when an outbreak of neurological and respiratory disease on pig farms in peninsular Malaysia caused 265 human cases, with 108 deaths. [15] [16] [17] The virus was isolated the following year in 1999. [1] This outbreak resulted in the culling of one million pigs. In Singapore, 11 cases, including one death, occurred in abattoir workers exposed to pigs imported from the affected Malaysian farms.

The name "Nipah" refers to the place, Sungai Nipah (literally nipah river') in Port Dickson, Negeri Sembilan, the source of the human case from which Nipah virus was first isolated. [18] [19]

The outbreak was originally mistaken for Japanese encephalitis, but physicians in the area noted that persons who had been vaccinated against Japanese encephalitis were not protected in the epidemic, and the number of cases among adults was unusual. [20] Although these observations were recorded in the first month of the outbreak, the Ministry of Health failed to take them into account, and launched a nationwide campaign to educate people on the dangers of Japanese encephalitis and its vector, Culex mosquitoes.[ citation needed ]

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.

During the 1999 outbreak of Nipah virus, which occurred among pig farmers, the majority of human infections stemmed from direct contact with sick pigs and the unprotected handling of secretions from the pigs.

Based on seroprevalence data and virus isolations, the primary reservoir for Nipah virus was identified as Pteropid fruit bats, including Pteropus vampyrus (large flying fox), and Pteropus hypomelanus (small flying fox), both found in Malaysia. [21]

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. In one outbreak, fruit orchards were in close proximity to the piggery, allowing the spillage of urine, faeces and partially eaten fruit onto the pigs. [22] Retrospective studies demonstrate that viral spillover into pigs may have been occurring, undetected, in Malaysia since 1996. [15] During 1998, viral spread was aided by the transfer of infected pigs to other farms, where new outbreaks occurred. [14]

Future threat

The Nipah virus has been classified by the Centers for Disease Control and Prevention as a Category C agent. [23] Nipah virus is one of several viruses identified by WHO as a potential cause of future epidemics in a new plan developed after the Ebola epidemic for urgent research and development toward new diagnostic tests, vaccines and medicines. [24] [25]

Prevention & Treatment

Presently, there are no dedicated drugs or vaccines available for the treatment or prevention of Nipah virus infection. The World Health Organization (WHO) has designated Nipah virus as a priority disease within the WHO Research and Development Blueprint. In cases of severe respiratory and neurological complications resulting from Nipah virus infection, healthcare professionals advise intensive supportive care as the primary treatment approach. [14]

In January 2024 a candidate vaccine, ChAdOx1 NipahB, commenced Phase I clinical trials after completing laboratory and animal testing. [26] [27]

Outbreaks of disease

Nipah virus infection outbreaks have been reported in Malaysia, Singapore, Bangladesh and India. The highest mortality due to Nipah virus infection has occurred in Bangladesh, where outbreaks are typically seen in winter. [28] Nipah virus first appeared in 1998, in peninsular Malaysia in pigs and pig farmers. By mid-1999, more than 265 human cases of encephalitis, including 105 deaths, had been reported in Malaysia, and 11 cases of either encephalitis or respiratory illness with one fatality were reported in Singapore. [29] In 2001, Nipah virus was reported from Meherpur District, Bangladesh [30] [31] and Siliguri, India. [30] The outbreak again appeared in 2003, 2004 and 2005 in Naogaon District, Manikganj District, Rajbari District, Faridpur District and Tangail District. [31] In Bangladesh there were also outbreaks in subsequent years. [32] In September 2021, Nipah virus resurfaced in Kerala, India claiming the life of a 12-year-old boy. [33] The most recent outbreak of Nipah virus occurred during January and February 2023 in Bangladesh with a total of 11 cases (ten confirmed, one probable) resulting in 8 deaths, a case fatality rate of 73%. [34] This outbreak resulted in the highest number of cases reported since 2015 in Bangladesh, and ten of the 11 cases during the 2023 outbreak had a confirmed history of consuming date palm sap. [34]

Locations of henipavirus outbreaks (red stars-Hendra virus; blue stars-Nipah virus) and distribution of henipavirus flying fox reservoirs (red shading-Hendra virus; blue shading-Nipah virus) Flying fox distribution.png
Locations of henipavirus outbreaks (red stars–Hendra virus; blue stars–Nipah virus) and distribution of henipavirus flying fox reservoirs (red shading–Hendra virus; blue shading–Nipah virus)

See also

Related Research Articles

<span class="mw-page-title-main">Encephalitis</span> Inflammation of the brain

Encephalitis is inflammation of the brain. The severity can be variable with symptoms including reduction or alteration in consciousness, headache, fever, confusion, a stiff neck, and vomiting. Complications may include seizures, hallucinations, trouble speaking, memory problems, and problems with hearing.

<i>Henipavirus</i> Genus of RNA viruses

Henipavirus is a genus of negative-strand RNA viruses in the family Paramyxoviridae, order Mononegavirales containing six established species, and numerous others still under study. Henipaviruses are naturally harboured by several species of small mammals, notably pteropid fruit bats, microbats of several species, and shrews. 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.

<i>Human metapneumovirus</i> Species of virus

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.

<span class="mw-page-title-main">Japanese encephalitis</span> Infection of the brain caused by the Japanese encephalitis virus

Japanese encephalitis (JE) is an infection of the brain caused by the Japanese encephalitis virus (JEV). While most infections result in little or no symptoms, occasional inflammation of the brain occurs. In these cases, symptoms may include headache, vomiting, fever, confusion and seizures. This occurs about 5 to 15 days after infection.

<span class="mw-page-title-main">Hendra virus</span> Species of virus

Hendra virus is a zoonotic virus found solely in Australia. First isolated in 1994, the virus has since been connected to numerous outbreaks of disease in domestic horses and seven human cases. Hendra virus belongs to the genus Henipavirus, which also contains the zoonotic Nipah virus. The reservoir species of Hendra virus are four species of bat within the genus Pteropus native to Australia.

<span class="mw-page-title-main">Viral hemorrhagic fever</span> Type of illnesses

Viral hemorrhagic fevers (VHFs) are a diverse group of animal and human illnesses. VHFs may be caused by five distinct families of RNA viruses: the families Filoviridae, Flaviviridae, Rhabdoviridae, and several member families of the Bunyavirales order such as Arenaviridae, and Hantaviridae. All types of VHF are characterized by fever and bleeding disorders and all can progress to high fever, shock and death in many cases. Some of the VHF agents cause relatively mild illnesses, such as the Scandinavian nephropathia epidemica, while others, such as Ebola virus, can cause severe, life-threatening disease.

Lymphocytic choriomeningitis (LCM) is a rodent-borne viral infectious disease that presents as aseptic meningitis, encephalitis or meningoencephalitis. Its causative agent is lymphocytic choriomeningitis mammarenavirus (LCMV), a member of the family Arenaviridae. The name was coined by Charles Armstrong in 1934.

<span class="mw-page-title-main">Human parainfluenza viruses</span> Viruses that cause human parainfluenza

Human parainfluenza viruses (HPIVs) are the viruses that cause human parainfluenza. HPIVs are a paraphyletic group of four distinct single-stranded RNA viruses belonging to the Paramyxoviridae family. These viruses are closely associated with both human and veterinary disease. Virions are approximately 150–250 nm in size and contain negative sense RNA with a genome encompassing about 15,000 nucleotides.

<i>Australian bat lyssavirus</i> Species of virus

Australian bat lyssavirus (ABLV), originally named Pteropid lyssavirus (PLV), is a enzootic virus closely related to the rabies virus. It was first identified in a 5-month-old juvenile black flying fox collected near Ballina in northern New South Wales, Australia, in January 1995 during a national surveillance program for the recently identified Hendra virus. ABLV is the seventh member of the genus Lyssavirus and the only Lyssavirus member present in Australia. ABLV has been categorized to the Phylogroup I of the Lyssaviruses.

<i>Andes orthohantavirus</i> Species of virus

Andes orthohantavirus (ANDV), a species of Orthohantavirus, is a major causative agent of hantavirus cardiopulmonary syndrome (HCPS) and hantavirus pulmonary syndrome (HPS) in South America. It is named for the Andes mountains of Chile and Argentina, where it was first discovered. Originating in the reservoir of rodents, Andes orthohantavirus is easily transmitted to humans who come into contact with infected rodents or their fecal droppings. However, infected rodents do not appear ill, so there is no readily apparent indicator to determine whether the rodent is infected or not. Additionally, Andes orthohantavirus, specifically, is the only hantavirus that can be spread by human to human contact via bodily fluids or long-term contact from one infected individual to a healthy person.

A breakthrough infection is a case of illness in which a vaccinated individual becomes infected with the illness, because the vaccine has failed to provide complete immunity against the pathogen. Breakthrough infections have been identified in individuals immunized against a variety of diseases including mumps, varicella (Chickenpox), influenza, and COVID-19. The characteristics of the breakthrough infection are dependent on the virus itself. Often, infection of the vaccinated individual results in milder symptoms and shorter duration than if the infection were contracted naturally.

<span class="mw-page-title-main">Influenza</span> Infectious disease

Influenza, commonly known as "the flu" or just "flu", is an infectious disease caused by influenza viruses. Symptoms range from mild to severe and often include fever, runny nose, sore throat, muscle pain, headache, coughing, and fatigue. These symptoms begin from one to four days after exposure to the virus and last for about 2–8 days. Diarrhea and vomiting can occur, particularly in children. Influenza may progress to pneumonia, which can be caused by the virus or by a subsequent bacterial infection. Other complications of infection include acute respiratory distress syndrome, meningitis, encephalitis, and worsening of pre-existing health problems such as asthma and cardiovascular disease.

<i>Zika virus</i> Species of flavivirus

Zika virus is a member of the virus family Flaviviridae. It is spread by daytime-active Aedes mosquitoes, such as A. aegypti and A. albopictus. Its name comes from the Ziika Forest of Uganda, where the virus was first isolated in 1947. Zika virus shares a genus with the dengue, yellow fever, Japanese encephalitis, and West Nile viruses. Since the 1950s, it has been known to occur within a narrow equatorial belt from Africa to Asia. From 2007 to 2016, the virus spread eastward, across the Pacific Ocean to the Americas, leading to the 2015–2016 Zika virus epidemic.

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.

<span class="mw-page-title-main">Bat virome</span> Group of viruses associated with bats

The bat virome is the group of viruses associated with bats. Bats host a diverse array of viruses, including all seven types described by the Baltimore classification system: (I) double-stranded DNA viruses; (II) single-stranded DNA viruses; (III) double-stranded RNA viruses; (IV) positive-sense single-stranded RNA viruses; (V) negative-sense single-stranded RNA viruses; (VI) positive-sense single-stranded RNA viruses that replicate through a DNA intermediate; and (VII) double-stranded DNA viruses that replicate through a single-stranded RNA intermediate. The greatest share of bat-associated viruses identified as of 2020 are of type IV, in the family Coronaviridae.

<span class="mw-page-title-main">Nipah virus infection</span> Disease caused by Nipah virus

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.

<span class="mw-page-title-main">1998–1999 Malaysia Nipah virus outbreak</span> Disease outbreak in Malaysia

The 1998–1999 Malaysia Nipah virus outbreak was a Nipah virus outbreak occurring from September 1998 to May 1999 in the states of Perak, Negeri Sembilan and Selangor in Malaysia. A total of 265 cases of acute encephalitis with 105 deaths caused by the virus were reported in the three states throughout the outbreak. The Malaysian health authorities at first thought that Japanese encephalitis (JE) was the cause of the infection. This misunderstanding hampered the deployment of effective measures to prevent the spread, before the disease was identified by a local virologist from the Faculty of Medicine, University of Malaya as a newly discovered agent. It was named Nipah virus (NiV). The disease was as deadly as the Ebola virus disease (EVD), but attacked the brain system instead of the blood vessels. University of Malaya's Faculty of Medicine and the University of Malaya Medical Centre played a major role in serving as a major referral centre for the outbreak, treating majority of the Nipah patients and was instrumental in isolating the novel virus and researched on its features.

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.

<span class="mw-page-title-main">Mòjiāng virus</span> Species of virus

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).

References

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