Orthohantavirus

Hantaviruses are sorted into Old World hantaviruses (OWHVs), which typically cause hemorrhagic fever with renal syndrome (HFRS) in Africa, Asia, and Europe, and New World hantaviruses (NWHVs) which are associated with hantavirus pulmonary syndrome (HPS) in the Americas. The case fatality rate of HFRS ranges from less than 1% to 15%, while for HPS it is 30–60%. The severity of symptoms of HFRS varies depending on the virus: Hantaan virus causes severe HFRS, Seoul virus moderate HFRS, Puumala virus mild HFRS, and Dobrava-Belgrade virus infection varies from mild to severe depending on genotype. The mild form of HFRS caused by Puumala virus and Dobrava-Belgrade virus is often called nephropathia epidemica (NE). Repeated infections of hantaviruses have not been observed, so recovering from infection likely grants life-long immunity. HFRS is characterized by five phases: febrile, hypotensive, low urine production (oliguria), high urine production (polyuria), and recovery. Symptoms usually occur 12–16 days after exposure to the virus. Acute kidney disease occurs with kidney swelling, excess protein in urine (proteinuria), and blood in urine (hematuria). Other symptoms include headache, lower back pain, nausea, vomiting, diarrhea, bloody stool, the appearance of spots on the skin (petechiae), and hemorrhaging in the respiratory tract. Renal failure leads oliguria, and restoration of kidney health comes with polyuria. In more mild cases, the different phases of HFRS may be hard to distinguish, or some phases may be absent, while in more severe cases, the phases may overlap. After the cardiopulmonary phase is resolved, polyuria occurs while recovery takes months. ==Transmission==

Hantaviruses that cause illness in humans are mainly transmitted by rodents. In rodents, hantaviruses usually cause an asymptomatic, persistent infection. Infected animals can spread the virus to uninfected animals through aerosols or droplets from their feces, urine, saliva, through consumption of contaminated food, from virus particles shed from skin or fur, via grooming, and zoology. There is also suspicion that Puumala virus can spread from person to person through blood and platelet transfusions. Hantaviruses that cause HFRS can be transmitted through the bites of mites and ticks. Research has also shown that pigs can be infected with Hantaan virus without severe symptoms and sows can transmit the virus to offspring through the placenta. Pig-to-human transmission may also be possible, as one swine breeder was infected with hantavirus with no contact with rodents or mites. Hantaan virus and Puumala virus have been detected in cattle, deer, and rabbits, and antibodies to Seoul virus have been detected in cats and dogs, but the role of these hosts for hantaviruses is unknown. shrews, and bats. Sewers and stormwater drainage systems may be inhabited by rodents, especially in areas with poor solid waste management. Maritime trade and travel have also been implicated in the spread of hantaviruses. Research results are inconsistent on whether urban living increases or decreases hantavirus incidence. Seroprevalence, which shows past infection to hantavirus, is consistently higher in occupations and areas that have greater exposure to rodents. Poor living conditions on battlefields, in military camps, and in refugee camps make soldiers and refugees at great risk of exposure as well. ==Environment==

's effect on local climates. Rodent species that carry hantaviruses inhabit a diverse range of habitats, including desert-like biomes, equatorial and tropical forests, swamps, savannas, fields, and salt marshes. In some places, such as South Korea, routine trapping of wild rodents is performed to surveil hantavirus circulation. Rainfall is consistently associated with hantavirus incidence in various patterns. Heavy rainfall is a risk factor for outbreaks in the following months, but may negatively affect incidence by flooding rodent burrows and nests. In places that have wet and dry seasons, infections are more common in the wet season than in the dry season. Low rainfall and drought are associated with decreased incidence since such conditions result in a smaller rodent population, but displacement of rodent populations via drought or flood can lead to an increase in rodent-human interactions and infections. In Europe, however, no association between rainfall and disease incidence has been found. Temperature has varying effects on hantavirus transmission. Higher temperatures create unfavorable environments for virus survival and decreases activity levels of Neotropic rodents, but it can cause rodents to seek shelter from heat in human settings and is beneficial for aerosol production. Lower temperature can prolong virus survival outside a host. Higher average winter temperature is associated with reduced survival of bank voles, the natural reservoir of Puumala virus, but increased survival of striped field mice in China, the natural reservoirs of Hantaan virus. Extreme temperatures, whether hot or cold, are associated with lower disease incidence. ==Genome and structure==

The genome of hantaviruses is segmented into three parts: the large (L), medium (M), and small (S) segments. Each part is a single-stranded negative-sense RNA strand and consists of 10,000–15,000 nucleotides in total. The L segment is about 6.6 kilobases (kb) in length of some orthohantaviruses also encodes the non-structural protein NS that inhibits interferon production in host cells. The untranslated regions at the ends of the genome are highly conserved and participate in the replication and transcription of the genome. or tubular. ==Life cycle==

Vascular endothelial cells and macrophages are the primary cells infected by hantaviruses. After entering a cell, virions form vesicles that are transported to early endosomes, then late endosomes and lysosomal compartments. A decrease in pH then causes the viral envelope to fuse with the endosome or lysosome. This fusion releases viral ribonucleoprotein complexes into the cell cytoplasm, which initiates transcription and replication by RdRp. RdRp transcribes viral -ssRNA into complementary positive-sense strands, then snatches 5′ ("five prime") ends of host messenger RNA (mRNA) to prepare mRNA for translation by host ribosomes to produce viral proteins. Complementary RNA strands are also used to produce copies of the genome, which are encapsulated by N proteins to form RNPs. During virion assembly, the glycoprotein precursor is cleaved in the endoplasmic reticulum into the Gn and Gc glycoproteins by host cell signal peptidases. Gn and Gc are modified by N-glycan chains, which stabilize the spike structure and assist in assembly in the Golgi apparatus for Old World hantaviruses or at the cell membrane for New World hantaviruses. Old World hantaviruses obtain their viral envelope from the Golgi apparatus and are then transported to the cell membrane in vesicles to leave the cell via exocytosis. On the other hand, New World hantavirus RNPs are transported to the cell membrane, where they bud from the surface of the cell to obtain their envelope and leave the cell. ==Evolution==

The most common form of evolution for hantaviruses is mutations through single nucleotide substitutions, insertions, and deletions. Within species, geography has affected the evolution of hantaviruses. For example, Hantaan virus and Seoul virus have both formed multiple lineages corresponding to their geographic distribution. Diploid progeny are also possible, in which virions may possess two of the same segment from two parent viruses. ==Classification==

Orthohantavirus belongs to the family Hantaviridae, which contains all hantaviruses. The genus has 37 species, listed hereafter with the exemplar virus of the species. In general, species bear the name of the exemplar virus with the suffix -ense. • Orthohantavirus andesense, Andes virus • Orthohantavirus artybashense, Artybash virus • Orthohantavirus asamaense, Asama virus • Orthohantavirus asikkalaense, Asikkala virus • Orthohantavirus bayoui, Bayou virus • Orthohantavirus boweense, Bowé virus • Orthohantavirus brugesense, Bruges virus • Orthohantavirus caobangense, Cao Bằng virus • Orthohantavirus carrizalense, Carrizal virus • Orthohantavirus chocloense, Choclo virus • Orthohantavirus dabieshanense, Dàbiéshān virus • Orthohantavirus delgaditoense, Caño Delgadito virus • Orthohantavirus dobravaense, Dobrava-Belgrade virus • Orthohantavirus fugongense, Fúgòng virus • Orthohantavirus hantanense, Hantaan virus • Orthohantavirus jejuense, Jeju virus • Orthohantavirus kenkemeense, Kenkeme virus • Orthohantavirus khabarovskense, Khabarovsk virus • Orthohantavirus lankaense, Lanka virus • Orthohantavirus luxiense, Lúxī virus • Orthohantavirus mamorense, Rio Mamoré virus • Orthohantavirus maporalense, Maporal virus • Orthohantavirus montanoense, Montaño virus • Orthohantavirus nigrorivense, Black Creek Canal virus • Orthohantavirus ozarkense, Ozark virus • Orthohantavirus prospectense, Prospect Hill virus • Orthohantavirus puumalaense, Puumala virus • Orthohantavirus rockportense, Rockport virus • Orthohantavirus sagercreekense Sager Creek virus • Orthohantavirus sangassouense, Sangassou virus • Orthohantavirus seoulense, Seoul virus • Orthohantavirus sinnombreense, Sin Nombre virus • Orthohantavirus tatenalense, Tatenale virus • Orthohantavirus thailandense, which contains Anjozorobe virus and Thailand virus • Orthohantavirus tigrayense, Tigray virus • Orthohantavirus tulaense, Tula virus • Orthohantavirus wufangense, Wùfeng Chodsigoa smithii orthohantavirus 1 Many other hantaviruses are unclassified, though some may be isolates of other viruses: • Academ virus • Adler virus • Alto Paraguay virus • Amga virus/Seewis virus • Anajatuba virus • Ash River virus • Asturias virus • Azagny virus • Belgrade virus • Biya river virus • Bloodland Lake virus • Blue River virus • Boginia virus • Calabazo virus • Camp Ripley virus • Castelo dos Sonhos virus • CGRn9415 virus • Dode virus • El Moro Canyon virus • Fox Creek virus • Fusong virus • Gōu virus • hantavirus sp. strain Tamarin/BRA/SM22/2014 • HoJo virus • Iamonia virus • Isla Vista virus • Jemez Springs virus • Jerboa hantavirus • Jurong virus • Kielder hantavirus • Laguna Negra virus • Landiras virus • Leakey virus • Lechiguanas virus • Liánghé virus • Lohja virus • Malacky virus • Muleshoe virus • Necocli virus • Orán virus • Oxbow virus • Playa de Oro virus • Powell Butte virus • Prairie vole virus • Qiān Hú Shān virus/Qiāndǎo Lake virus • Rio Mearim virus • Río Segundo virus • Sapporo rat virus • Sarufutsu virus • Serang virus • Shěnyáng virus • Taimyr virus • Tanganya virus • Tualatin River virus • Uurainen virus • Vladivostok virus • Yakeshi virus • Yuánjiāng virus ==History==

Hantavirus hemorrhagic disease was likely first described in the Huangdi Neijing, an ancient Chinese medical text, in Imperial China during the Warring States Period of 475–221 BCE. Over time, hundreds of bunyaviruses were discovered but could not be accommodated within the genera of the Bunyaviridae family. To address this, in 2017 bunyaviruses were elevated to the rank of order, Bunyavirales, and hantaviruses, along with the other bunyavirus genera, were elevated to the rank of family. Hantaviruses, also called hantavirids, now also refer to members of the family Hantaviridae. The prior genus of Hantavirus was renamed Orthohantavirus to distinguish them from members of the family, and the genus's members are often called orthohantaviruses. In 2019, additional genera, subfamilies, and families were created to classify non-rodent hantaviruses, and in 2023 binomial nomenclature was adopted for hantaviruses. ==Notes==