Sepik virus

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Sepik virus
Virus classification Red Pencil Icon.png
(unranked): Virus
Realm: Riboviria
Kingdom: Orthornavirae
Phylum: Kitrinoviricota
Class: Flasuviricetes
Order: Amarillovirales
Family: Flaviviridae
Genus: Flavivirus
Species:
Sepik virus

Sepik virus (SEPV) is an arthropod-borne virus (arbovirus) of the genus Flavivirus and family Flaviviridae . [1] Flaviviridae is one of the most well characterized viral families, as it contains many well-known viruses that cause diseases that have become very prevalent in the world, like Dengue virus. [2] The genus Flavivirus is one of the largest viral genera and encompasses over 50 viral species, including tick and mosquito borne viruses like Yellow fever virus and West Nile virus. [1] Sepik virus is much less well known and has not been as well-classified as other viruses because it has not been known of for very long. Sepik virus was first isolated in 1966 from the mosquito Mansonia septempunctata, and it derives its name from the Sepik River area in Papua New Guinea, where it was first found. [3] The geographic range of Sepik virus is limited to Papua New Guinea, due to its isolation. [4]

Contents

Map of Papua New Guinea, the only place Sepik virus has been found Papua New Guinea map.png
Map of Papua New Guinea, the only place Sepik virus has been found

Arboviruses are a continuing threat to public health in Papua New Guinea especially because of lack of surveillance and reporting, so much of the prevalence of disease due to these viruses are unknown in that area. Arboviruses cause outbreaks when the virus that infects an endemic population spreads through a vector like mosquitoes or ticks to humans. [5] While the principal host species for Sepik virus is still unknown, it has been discovered that the primary mosquito species that transmits Sepik virus is Mansoniaseptempunctata. [4] This differs from other related viruses, as most of the well-classified mosquito borne viruses public health officials focus on are transmitted by Culex and Aedes aegypti mosquito species. [2] [6]

Viral classification and evolution

Sepik virus is in the genus Flavivirus, which means it is similar to yellow fever virus, as Yellow Fever Virus is the type virus for the family. [7] It is also an arbovirus, so the virus is transmitted by an arthropod vector. The genus Flavivirus can further be broken down into clades based on whether the vector that transmits the virus to humans, and what the vector is. If the vector is known, it forms a clade, which is further broken down into type of vector. In the known vector clade, there is a mosquito group and a tick group, which diverged early in the phylogeny and do not have much overlap, ecologically. [7] The mosquito group is further divided into the types of diseases the virus causes, like neurotropic viruses and hemorrhagic disease viruses. Neurotropic viruses like Japanese encephalitis virus cause encephalitic disease and is commonly spread by Culex mosquito species and has a reservoir in birds, while hemorrhagic disease viruses like Yellow Fever are commonly spread by Aedes mosquito species and have primate hosts. [2] Sepik virus is classified as a hemorrhagic disease virus because it is in the Yellow fever group, as it is most closely related to Yellow Fever virus. However, Sepik virus does not have the same pathogenicity or virulence as Yellow Fever virus, as it is not known to cause hemorrhagic fever, but rather a febrile illness. [4]

Viral structure

Similar to other viruses in the genus Flavivirus, Sepik virus is a circular, enveloped virus that displays icosahedral symmetry in the nucleocapsid. [3] The virion is relatively small, only about 50 nm in diameter. [8] The virus particle contains three major structural proteins; there are two membrane-associated proteins, the envelope protein (E) and membrane protein (M). The virus also has a capsid protein (C) that protects the genome from the environment, which could cause the genome to dry out or become degraded. The capsid is mainly protein, but 17% of the capsid are lipids by weight, which were derived from the host cell membrane; the capsid is also about 9% carbohydrate by weight in the form of glycolipids and glycoproteins. [8]

Viral genome

The genome for Sepik virus is a non-segmented, single stranded, positive sense RNA molecule that is about 10.79 kilobases in length. [3] The genome consists of a short non-coding region at the 5’ end, a single long open reading frame (ORF) that contains the genes for all the genes the virus produces, and a non-coding region at the 3’ end and the genome does not have a poly-A tail typically seen at the end of mRNA molecules. [3] The non-coding regions are useful in determining phylogenetic relationships between viruses within the Flavivirus genus, as well as within groups, like the Yellow Fever virus group. [7] The non-coding regions also contain motifs that are important in viral translation, replication and packaging. [3] The genome serves as both genomic data and mRNA, encoding 3 structural proteins necessary for the virion and 8 non-structural proteins necessary for replication. The genome also contains a type I cap and a conserved stem loop at the 5’ end, labeled as m7GpppAmp, that is not seen in viruses in other families or genera. [8] The cap serves as an initiation site for transcription, as well as stability to the mRNA. [9]

Replication cycle

Entry

Entry of Sepik virus into the cell is mediated by the envelope protein (E), which is the viral entry protein. [10] The envelope protein binds to the host cell receptor which then signals to the cell to bring the virus inside using endocytosis. The envelope protein then helps the viral envelope fuse to the host cell membrane in order to release the viral capsid into the cell. [10]

Replication and transcription

Once the genome is in the cell, replication occurs along the membrane of the rough endoplasmic reticulum. Replication usually occurs in membrane invaginations to shield the replicating genome from host defenses like RNA interference, because single stranded positive RNA viruses replicate through a double stranded RNA intermediate. [11] The genome also functions as mRNA and the virus uses the host cell’s machinery to translate one long polyprotein containing both the structural and non-structural proteins. [11] This one long polyprotein is later cleaved into the capsid, envelope and membrane protein, and also proteins that are not assembled into the virion, which are denoted as non-structural proteins. The non-structural proteins function in viral replication and assembly. These proteins are named NS1, NS2A, NS2B, NS3, NS4A, NS4B, NS5, and NS2K, where NS denotes “non-structural”. [11] NS3 has enzymatic activity as a helicase and protease, [11] while NS5 is an RNA dependent RNA polymerase, allowing the virus to replicate a new (+)RNA genome by creating a complementary (-)RNA strand and using that as a template for the genome. [11] The other non-structural proteins function in RNA replication, viral assembly and release, processing the viral polyprotein and inhibiting the host’s innate immunity, like inhibiting interferon signaling. [11] [8]

Assembly and release

There is no known structured nucleocapsid for any viruses in the genus Flavivirus, as no viruses belonging to the genus have been seen using cryo-electron microscopy. [12] Therefore, assembly of the virion likely consists of the capsid protein (C) and the genomic RNA becoming aggregated and condensed, with the capsid protein acting as a charge neutralizer for the RNA, to eventually form a small particle that does not have any contact with the envelope. [12] Virions are released by budding of the capsid protein and the RNA into the endoplasmic reticulum membrane to form a lipid envelope that are sporadically ingrained with glycoproteins, like the envelope (E) glycoprotein that is used for entry into the next host cell. [10] The virions are later secreted out of the host cell to infect new, susceptible cells.[ citation needed ]

Transmission

This diagram shows how Sepik virus gets from the natural host of the virus to humans to make them sick. Arbovirus Transmission Cycle.jpg
This diagram shows how Sepik virus gets from the natural host of the virus to humans to make them sick.

Sepik virus, like all other arboviruses, is transmitted from a host reservoir to humans through a viral vector. Some arboviruses can be maintained in a population with minimal input from the reservoir, meaning the vector can use infected humans as a source of the virus to spread to new, susceptible people. [13] However, Sepik virus cannot be maintained in the population and therefore cannot be passed via mosquito vector between humans. This means that the host reservoir is the only known source of Sepik virus, but the host reservoir is unknown at this time. [4]

Associated diseases

Sepik virus causes a fever in humans, much like other viruses in the genus Flavivirus like dengue virus and Yellow fever virus. [2] However, Sepik virus is only known to cause a non-severe febrile fever and not hemorrhagic fever like the more well classified viruses. Fever as a result of Sepik virus infection has only been seen in Papua New Guinea and has remained isolated from the rest of the world. However, reporting and surveillance for this fever is lacking, so spread of the vector and Sepik virus fever may have begun to spread outside its normal range, and no notice has been taken. [4]

Arboviruses, mainly highly pathogenic ones like Yellow Fever virus or Dengue virus, are important emerging pathogens in many tropical and developing countries because of the high prevalence of the viral vector and many countries have poor sanitation and do not have vector control methods. [5] It is important to note that the known geographic regions many arboviruses are currently found are not concrete, as changing global temperatures contribute to the widening of vector habitat, as many arboviruses that have been limited to tropical zones are now seen further into the temperate zones as the vector, mainly mosquitoes, moves into new areas and can infect naïve populations. [13]

Related Research Articles

<i>Flaviviridae</i> Family of viruses

Flaviviridae is a family of enveloped positive-strand RNA viruses which mainly infect mammals and birds. They are primarily spread through arthropod vectors. The family gets its name from the yellow fever virus; flavus is Latin for "yellow", and yellow fever in turn was named because of its propensity to cause jaundice in victims. There are 89 species in the family divided among four genera. Diseases associated with the group include: hepatitis (hepaciviruses), hemorrhagic syndromes, fatal mucosal disease (pestiviruses), hemorrhagic fever, encephalitis, and the birth defect microcephaly (flaviviruses).

<i>Hepadnaviridae</i> Family of viruses

Hepadnaviridae is a family of viruses. Humans, apes, and birds serve as natural hosts. There are currently 18 species in this family, divided among 5 genera. Its best-known member is hepatitis B virus. Diseases associated with this family include: liver infections, such as hepatitis, hepatocellular carcinomas, and cirrhosis. It is the sole accepted family in the order Blubervirales.

<i>Flavivirus</i> Genus of viruses

Flavivirus is a genus of positive-strand RNA viruses in the family Flaviviridae. The genus includes the West Nile virus, dengue virus, tick-borne encephalitis virus, yellow fever virus, Zika virus and several other viruses which may cause encephalitis, as well as insect-specific flaviviruses (ISFs) such as cell fusing agent virus (CFAV), Palm Creek virus (PCV), and Parramatta River virus (PaRV). While dual-host flaviviruses can infect vertebrates as well as arthropods, insect-specific flaviviruses are restricted to their competent arthropods. The means by which flaviviruses establish persistent infection in their competent vectors and cause disease in humans depends upon several virus-host interactions, including the intricate interplay between flavivirus-encoded immune antagonists and the host antiviral innate immune effector molecules.

<i>Dengue virus</i> Species of virus

Dengue virus (DENV) is the cause of dengue fever. It is a mosquito-borne, single positive-stranded RNA virus of the family Flaviviridae; genus Flavivirus. Four serotypes of the virus have been found, a reported fifth has yet to be confirmed, all of which can cause the full spectrum of disease. Nevertheless, scientists' understanding of dengue virus may be simplistic as, rather than distinct antigenic groups, a continuum appears to exist. This same study identified 47 strains of dengue virus. Additionally, coinfection with and lack of rapid tests for Zika virus and chikungunya complicate matters in real-world infections.

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

Rubella virus (RuV) is the pathogenic agent of the disease rubella, transmitted only between humans via the respiratory route, and is the main cause of congenital rubella syndrome when infection occurs during the first weeks of pregnancy.

<span class="mw-page-title-main">Viral protein</span>

A viral protein is both a component and a product of a virus. Viral proteins are grouped according to their functions, and groups of viral proteins include structural proteins, nonstructural proteins, regulatory proteins, and accessory proteins. Viruses are non-living and do not have the means to reproduce on their own, instead depending on their host cell's resources in order to reproduce. Thus, viruses do not code for many of their own viral proteins, and instead use the host cell's machinery to produce the viral proteins they require for replication.

<i>Tick-borne encephalitis virus</i> Species of virus

Tick-borne encephalitis virus (TBEV) is a positive-strand RNA virus associated with tick-borne encephalitis in the genus Flavivirus.

<i>Alphavirus</i> Genus of viruses

Alphavirus is a genus of RNA viruses, the sole genus in the Togaviridae family. Alphaviruses belong to group IV of the Baltimore classification of viruses, with a positive-sense, single-stranded RNA genome. There are 32 alphaviruses, which infect various vertebrates such as humans, rodents, fish, birds, and larger mammals such as horses, as well as invertebrates. Alphaviruses that could infect both vertebrates and arthropods are referred dual-host alphaviruses, while insect-specific alphaviruses such as Eilat virus and Yada yada virus are restricted to their competent arthropod vector. Transmission between species and individuals occurs mainly via mosquitoes, making the alphaviruses a member of the collection of arboviruses – or arthropod-borne viruses. Alphavirus particles are enveloped, have a 70 nm diameter, tend to be spherical, and have a 40 nm isometric nucleocapsid.

<i>Orbivirus</i> Genus of viruses

Orbivirus is a genus of double-stranded RNA viruses in the family Reoviridae and subfamily Sedoreovirinae. Unlike other reoviruses, orbiviruses are arboviruses. They can infect and replicate within a wide range of arthropod and vertebrate hosts. Orbiviruses are named after their characteristic doughnut-shaped capsomers.

<i>Pestivirus</i> Genus of viruses

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.

<span class="mw-page-title-main">Viral disease</span> Human, animal or plant disease resulting from a viral infection

A viral disease occurs when an organism's body is invaded by pathogenic viruses, and infectious virus particles (virions) attach to and enter susceptible cells.

Batai orthobunyavirus (BATV) is a RNA virus belonging to order Bunyavirales, genus Orthobunyavirus.

Entebbe bat virus is an infectious disease caused by a Flavivirus that is closely related to yellow fever.

Spondweni virus is an arbovirus, or arthropod-borne virus, which is a member of the family Flaviviridae and the genus Flavivirus. It is part of the Spondweni serogroup which consists of the Sponweni virus and the Zika virus (ZIKV). The Spondweni virus was first isolated in Nigeria in 1952, and ever since, SPONV transmission and activity have been reported throughout Africa. Its primary vector of transmission is the sylvatic mosquito Aedes circumluteolus, though it has been isolated from several different types of mosquito. Transmission of the virus into humans can lead to a viral infection known as Spondweni fever, with symptoms ranging from headache and nausea to myalgia and arthralgia. However, SPONV is phylogenetically close to the ZIKV, it is commonly misdiagnosed as ZIKV along with other viral illnesses.

<i>West Nile virus</i> Species of flavivirus causing West Nile fever

West Nile virus (WNV) is a single-stranded RNA virus that causes West Nile fever. It is a member of the family Flaviviridae, from the genus Flavivirus, which also contains the Zika virus, dengue virus, and yellow fever virus. The virus is primarily transmitted by mosquitoes, mostly species of Culex. The primary hosts of WNV are birds, so that the virus remains within a "bird–mosquito–bird" transmission cycle. The virus is genetically related to the Japanese encephalitis family of viruses.

<i>Middelburg virus</i> Species of virus

Middelburg virus (MIDV) is an alphavirus of the Old World Group that has likely endemic and zoonotic potential. It is of the viral family Togaviridae. It was isolated from mosquitos in 1957 in South Africa, MDIV antigens have now been found in livestock, horses, and humans.

Umatilla virus(UMAV) is a dsRNA virus in the family Reoviridae, subfamily Sedoreovirinae, and the genus Orbivirus. This arbovirus was first isolated in 1969 in Umatilla County, Oregon in a group of Culex pipiens mosquitoes. The viral host is the Passer domesticus bird with the vectors being Culex mosquitoes.

Yokose virus (YOKV) is in the genus Flavivirus of the family Flaviviridae. Flaviviridae are often found in arthropods, such as mosquitoes and ticks, and may also infect humans. The genus Flavivirus includes over 50 known viruses, including Yellow Fever, West Nile Virus, Zika Virus, and Japanese Encephalitis. Yokose virus is a new member of the Flavivirus family that has only been identified in a few bat species. Bats have been associated with several emerging zoonotic diseases such as Ebola and SARS.

<i>Modoc virus</i> Species of virus

Modoc virus (MODV) is a rodent-associated flavivirus. Small and enveloped, MODV contains positive single-stranded RNA. Taxonomically, MODV is part of the Flavivirus genus and Flaviviridae family. The Flavivirus genus includes nearly 80 viruses, both vector-borne and no known vector (NKV) species. Known flavivirus vector-borne viruses include Dengue virus, Yellow Fever virus, tick-borne encephalitis virus, and West Nile virus.

Rio Negro virus is an alphavirus that was first isolated in Argentina in 1980. The virus was first called Ag80-663 but was renamed to Rio Negro virus in 2005. It is a former member of the Venezuelan equine encephalitis complex (VEEC), which are a group of alphaviruses in the Americas that have the potential to emerge and cause disease. Río Negro virus was recently reclassified as a distinct species. Closely related viruses include Mucambo virus and Everglades virus.

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