Orthohantavirus is a genus of viruses which includes all hantaviruses that cause disease in humans. Hantaviruses are naturally found primarily in rodents. In general, each hantavirus is carried by one rodent species and each rodent that carries a hantavirus carries one hantavirus species. Hantaviruses in their natural reservoirs usually cause an asymptomatic, persistent infection. In humans, however, hantaviruses cause two diseases: hemorrhagic fever with renal syndrome (HFRS) and hantavirus pulmonary syndrome (HPS). HFRS is mainly caused by hantaviruses in Africa, Asia, and Europe, called Old World hantaviruses, and HPS is usually caused by hantaviruses in the Americas, called New World hantaviruses.

Hantaviruses are transmitted mainly through aerosols and droplets that contain rodent excretions, as well as through contaminated food, bites, and scratches. Environmental factors such as rainfall, temperature, and humidity influence transmission. HFRS is marked by kidney disease with kidney swelling, excess protein in urine, and blood in urine. The case fatality rate of HFRS varies from less than 1% to 15% depending on the virus. A mild form of HFRS called nephropathia epidemica is often caused by Puumala virus and Dobrava-Belgrade virus. For HPS, initial symptoms are flu-like, with fever, headache, and muscle pain, followed by sudden respiratory failure. HPS has a higher case fatality rate than HFRS, at 30–60%. For both HFRS and HPS, illness is the result of increased vascular permeability, decreased platelet count, and overreaction of the immune system.

The hantavirus genome consists of three single-stranded negative-sense RNA segments that encode one protein each: an RNA-dependent RNA polymerase (RdRp), a spike glycoprotein precursor, and the N protein. Segments are encased in N proteins to form ribonucleoprotein (RNP) complexes that each have a copy of RdRp attached. RNP complexes are surrounded by a lipid envelope that has spike proteins emanating from its surface. Replication begins when spikes attach to the surface of cells. After entering the cell, the envelope fuses with endosomes and lysosomes, which empties RNPs into the cytoplasm. RdRp then transcribes the genome to produce messenger RNA (mRNA) for translation by host ribosomes to produce viral proteins and replicates the genome for progeny viruses. Old World hantaviruses assemble in the Golgi apparatus and obtain their envelope from it, before being transported to the cell membrane to leave the cell via exocytosis. New World hantaviruses assemble near the cell membrane and obtain their envelope from it as they leave the cell by budding from its surface.

Hantaviruses were first discovered following the Korean War. During the war, HFRS was a common ailment in soldiers stationed near the Hantan River. The first hantavirus was isolated in 1978 in South Korea and was named Hantaan virus. It was shown to be responsible for the outbreak during the war. Within a few years, other hantaviruses that cause HFRS were discovered throughout Eurasia. In 1982, the World Health Organization gave HFRS its name, and in 1987, hantaviruses were classified as a genus for the first time. In 1993, an outbreak of HPS occurred in the Four Corners region in the United States, which led to the discovery of pathogenic New World hantaviruses and the second disease caused by hantaviruses. Since then, hantaviruses have been found not just in rodents but also in moles, shrews, and bats.

Disease

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 to 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, recovery typically takes 3 to 6 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. It can reportedly spread through human saliva, airborne droplets from coughing and sneezing, and possibly to newborns through breast milk or the placenta.

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; 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. 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, 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.

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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.

  • 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

thumb|alt=A grainy portrait photograph of Ho Wang Lee|Ho Wang Lee, 1972

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.

In 1993, an outbreak of highly lethal acute respiratory distress syndrome occurred in the Four Corners region of the United States. This outbreak was determined to be caused by a hantavirus, now named Sin Nombre virus, and represented the first confirmed instance of pathogenic hantaviruses in the Americas as well as the discovery of a new type of disease caused by hantaviruses. The new disease was named hantavirus pulmonary syndrome. In subsequent years, numerous other hantaviruses were discovered in the Americas.

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 and subfamilies were created to classify non-rodent hantaviruses,