''Orthohantavirus'' is a genus of single-stranded, enveloped,

negative-sense In molecular biology and genetics, the sense of a nucleic acid molecule, particularly of a strand of DNA or RNA, refers to the nature of the roles of the strand and its complementarity (molecular biology), complement in specifying a sequence of am ...

RNA virus An RNA virus is a virusother than a retrovirusthat has ribonucleic acid (RNA) as its genetic material. The nucleic acid is usually single-stranded RNA ( ssRNA) but it may be double-stranded (dsRNA). Notable human diseases caused by RNA viruses ...

es in the family ''

Hantaviridae ''Hantaviridae'' is a family of viruses in the order ''Bunyavirales''. It is named for the Hantan River area in South Korea where an early outbreak of one of its species was observed. Taxonomy * '' Actantavirinae'' ** '' Actinovirus'' * '' Agan ...

'' within the order ''

Bunyavirales ''Bunyavirales'' is an order of segmented negative-strand RNA viruses with mainly tripartite genomes. Member viruses infect arthropods, plants, protozoans, and vertebrates. It is the only order in the class ''Ellioviricetes''. The name ''Bunyavir ...

''. Members of this genus may be called orthohantaviruses or simply hantaviruses. Orthohantaviruses typically cause chronic

asymptomatic infection In medicine, any disease is classified asymptomatic if a patient tests as carrier for a disease or infection but experiences no symptoms. Whenever a medical condition fails to show noticeable symptoms after a diagnosis it might be considered asym ...

rodent Rodents (from Latin , 'to gnaw') are mammals of the order Rodentia (), which are characterized by a single pair of continuously growing incisors in each of the upper and lower jaws. About 40% of all mammal species are rodents. They are na ...

s. Humans may become infected with hantaviruses through contact with rodent urine, saliva, or feces. Some strains cause potentially fatal diseases in humans, such as

hantavirus hemorrhagic fever with renal syndrome Hantavirus hemorrhagic fever with renal syndrome (HFRS) is a group of clinically similar illnesses caused by species of hantaviruses. It is also known as Korean hemorrhagic fever and epidemic hemorrhagic fever. It is found in Europe, Asia, and Af ...

(HFRS), or

hantavirus pulmonary syndrome Hantavirus pulmonary syndrome (HPS) is one of two potentially fatal syndromes of zoonotic origin caused by species of hantavirus. These include Black Creek Canal virus (BCCV), New York orthohantavirus (NYV), Monongahela virus (MGLV), ''Sin Nomb ...

(HPS), also known as hantavirus cardiopulmonary syndrome (HCPS), while others have not been associated with known human disease (e.g.

Prospect Hill virus ''Prospect Hill orthohantavirus'' is a single-stranded, negative-sense Hantaan-like zoonotic RNA virus isolated from meadow voles and microtine and other cricetid rodents in the United States. It has a widespread distribution in Pennsylvania, Mar ...

). HPS (HCPS) is a "rare respiratory illness associated with the inhalation of aerosolized rodent excreta (urine and feces) contaminated by hantavirus particles." Human infections of hantaviruses have almost entirely been linked to human contact with rodent excrement; however, in 2005 and 2019, human-to-human transmission of the

Andes 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 ...

was reported in South America. Orthohantaviruses are named for the Greek word ''ortho''- meaning "straight" or "true" and for the

Hantan River The Hantan River is a river in South Korea, flowing through Gangwon and Gyeonggi Provinces. It is a tributary of the Imjin River, which eventually joins the Han River and empties into the Yellow Sea. The Hantan River is a popular site for white- ...

South Korea South Korea, officially the Republic of Korea (ROK), is a country in East Asia, constituting the southern part of the Korea, Korean Peninsula and sharing a Korean Demilitarized Zone, land border with North Korea. Its western border is formed ...

, where the first member species (

Hantaan virus ''Hantaan orthohantavirus'' (HTNV) is an enveloped, single-stranded, negative-sense RNA virus species of Old World ''Orthohantavirus''. It is the causative agent of Korean hemorrhagic fever in humans. It is named for the Hantan River in South K ...

) was identified and isolated in 1976 by

Ho Wang Lee Ho Wang Lee (26 October 1928 – 5 July 2022) was a South Korean physician, epidemiologist, and virologist. He was the first person in the history of medicine to be the one chiefly responsible for all 3 of the following steps: (1) discovery of ...

Disease

Hantavirus infections in humans are associated with two diseases:

hemorrhagic fever with renal syndrome Hantavirus hemorrhagic fever with renal syndrome (HFRS) is a group of clinically similar illnesses caused by species of hantaviruses. It is also known as Korean hemorrhagic fever and epidemic hemorrhagic fever. It is found in Europe, Asia, and A ...

(HFRS) and

(HPS), caused by Old World and New World hantaviruses, respectively. A common feature of the two diseases is increased vascular permeability, which causes

hypotension Hypotension is low blood pressure. Blood pressure is the force of blood pushing against the walls of the arteries as the heart pumps out blood. Blood pressure is indicated by two numbers, the systolic blood pressure (the top number) and the dias ...

thrombocytopenia Thrombocytopenia is a condition characterized by abnormally low levels of platelets, also known as thrombocytes, in the blood. It is the most common coagulation disorder among intensive care patients and is seen in a fifth of medical patients an ...

, and

leukocytosis Leukocytosis is a condition in which the white cell (leukocyte count) is above the normal range in the blood. It is frequently a sign of an inflammatory response, most commonly the result of infection, but may also occur following certain parasi ...

. The pulmonary illness is the more fatal of the two, whereas the hemorrhagic fever is much more common. Treatment for both is primarily supportive as there is no specific treatment for hantavirus infections. While many hantaviruses cause either of the two diseases, some are not known to cause illness, such as the ''

Prospect Hill orthohantavirus ''Prospect Hill orthohantavirus'' is a single-stranded, negative-sense Hantaan-like zoonotic RNA virus isolated from meadow voles and microtine and other cricetid rodents in the United States. It has a widespread distribution in Pennsylvania, Mar ...

''.

Hemorrhagic fever with renal syndrome

Hemorrhagic fever with renal syndrome (HFRS) is caused chiefly by hantaviruses in Asia and Europe. Clinical presentation varies from subclinical to fatal, depending on the virus. After an

incubation period Incubation period (also known as the latent period or latency period) is the time elapsed between exposure to a pathogenic organism, a chemical, or radiation, and when symptoms and signs are first apparent. In a typical infectious disease, the i ...

of 2–4 weeks, the typical illness starts with non-specific symptoms such as high fever, chills, headache, backache, abdominal pains, nausea, and vomiting. After the initial period, bleeding under the skin begins, often paired with low blood pressure, followed by further internal bleeding throughout the body.

Renal dysfunction Kidney failure, also known as end-stage kidney disease, is a medical condition in which the kidneys can no longer adequately filter waste products from the blood, functioning at less than 15% of normal levels. Kidney failure is classified as eit ...

leading to further health issues begins thereafter, which may cause death. A more mild form of HFRS that occurs in Europe is called "nephropathia epidemica" (NE).

Trench nephritis Trench nephritis, also known as war nephritis, is a kidney infection, first recognised by medical officers as a new disease during the early part of the First World War and distinguished from the then-understood acute nephritis by also having bron ...

during World War I is now thought to have been HFRS.

Hantavirus pulmonary syndrome

Hantavirus pulmonary syndrome (HPS), also called hantavirus cardiopulmonary syndrome (HCPS), is usually caused by hantaviruses in the Americas. Its incubation period ranges from 16 to 24 days. Illness initially shows similar symptoms as HFRS. After a few days of non-specific symptoms, sudden onset of progressive, or productive, coughing, shortness of breath, and elevated heart rate occur due to fluid buildup in the lungs. These symptoms are accompanied by impairment of

lymphoid organs The lymphatic system, or lymphoid system, is an organ system in vertebrates that is part of the immune system, and complementary to the circulatory system. It consists of a large network of lymphatic vessels, lymph nodes, lymphatic or lymphoid ...

. Death from

cardiovascular shock Shock is the state of insufficient blood flow to the tissues of the body as a result of problems with the circulatory system. Initial symptoms of shock may include weakness, fast heart rate, fast breathing, sweating, anxiety, and increased thi ...

may occur rapidly after the appearance of severe symptoms. While HCPS is typically associated with New World hantaviruses, the ''Puumala orthohantavirus'' in Europe has also caused the syndrome on rare occasions.

Transmission

Hantaviruses are transmitted by contact with the bodily fluids of rodents, particularly from saliva from bites and especially from inhalation of viral particles from urine and feces in

aerosol An aerosol is a suspension (chemistry), suspension of fine solid particles or liquid Drop (liquid), droplets in air or another gas. Aerosols can be natural or Human impact on the environment, anthropogenic. Examples of natural aerosols are fog o ...

s. The manner of transmission is the same for both diseases caused by hantaviruses. Among the HCPS-causing hantaviruses is the '' Andes orthohantavirus'', which is the only hantavirus confirmed to be capable of spreading from person to person, though this is rare.

Characteristics

Structure

Hantavirus virions are about 120–160 nm in diameter. The lipid bilayer of the

viral envelope 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. Numerous human pathogenic viruses in circulation are encase ...

is about 5 nm thick and is embedded with viral surface proteins to which sugar residues are attached. These glycoproteins, known as Gn and Gc, are encoded by the M segment of the viral genome. They tend to associate (

heterodimerize In biochemistry, a protein dimer is a macromolecular complex formed by two protein monomers, or single proteins, which are usually non-covalently bound. Many macromolecules, such as proteins or nucleic acids, form dimers. The word ''dimer'' ha ...

) with each other and have both an interior tail and an exterior domain that extends to about 6 nm beyond the envelope surface. Inside the envelope are the nucleocapsids. These are composed of many copies of the nucleocapsid protein N, which interact with the three segments of the viral genome to form helical structures. The virally encoded

RNA polymerase In molecular biology, RNA polymerase (abbreviated RNAP or RNApol), or more specifically DNA-directed/dependent RNA polymerase (DdRP), is an enzyme that synthesizes RNA from a DNA template. Using the enzyme helicase, RNAP locally opens the ...

is also found in the interior. By mass, the virion is greater than 50% protein, 20–30% lipid, and 2–7% carbohydrate. The density of the virions is 1.18 g/cm³. These features are common to all members of the family ''Hantaviridae''.

Genome

The genome of hantaviruses is negative-sense, single-stranded RNA. Their genomes are composed of three segments: the small (S), medium (M), and large (L) segments. The S segment, 1-3 kilobases (kb) in length, encodes for the

nucleocapsid A capsid is the protein shell of a virus, enclosing its genetic material. It consists of several oligomeric (repeating) structural subunits made of protein called protomers. The observable 3-dimensional morphological subunits, which may or may ...

(N) protein. The M segment, 3.2-4.9 kb in length, encodes a

glycoprotein Glycoproteins are proteins which contain oligosaccharide chains covalently attached to amino acid side-chains. The carbohydrate is attached to the protein in a cotranslational or posttranslational modification. This process is known as glycos ...

precursor

polyprotein Proteolysis is the breakdown of proteins into smaller polypeptides or amino acids. Uncatalysed, the hydrolysis of peptide bonds is extremely slow, taking hundreds of years. Proteolysis is typically catalysed by cellular enzymes called protease ...

that is co-translationally cleaved into the envelope glycoproteins Gn and Gc, alternatively called G1 and G2. The L segment, 6.8–12 kb in length, encodes the L protein which functions primarily as the viral

RNA-dependent RNA polymerase RNA-dependent RNA polymerase (RdRp) or RNA replicase is an enzyme that catalyzes the replication of RNA from an RNA template. Specifically, it catalyzes synthesis of the RNA strand complementary to a given RNA template. This is in contrast to t ...

used for transcription and replication. Within

virion A virus is a submicroscopic infectious agent that replicates only inside the living cells of an organism. Viruses infect all life forms, from animals and plants to microorganisms, including bacteria and archaea. Since Dmitri Ivanovsky's 1 ...

s, the genomic RNAs of hantaviruses are thought to complex with the N protein to form helical nucleocapsids, the RNA component of which circularizes due to sequence complementarity between the 5' and 3' terminal sequences of genomic segments. As with other ''Bunyavirales'', each of the three segments has a consensus 3'-terminal

nucleotide Nucleotides are organic molecules consisting of a nucleoside and a phosphate. They serve as monomeric units of the nucleic acid polymers – deoxyribonucleic acid (DNA) and ribonucleic acid (RNA), both of which are essential biomolecules wi ...

sequence (AUCAUCAUC), which is complementary to the 5'-terminal sequence and is distinct from those of the other four genera in the family. These sequences appear to form panhandle structure which seem likely to play a role in replication and

encapsidation {{Short pages monitor

Viral entry Viral entry is the earliest stage of infection in the viral life cycle, as the virus comes into contact with the host cell (biology), cell and introduces viral material into the cell. The major steps involved in viral entry are shown below. Desp ...

into host cells initiates by binding to surface cell receptors.

Integrin Integrins are transmembrane receptors that facilitate cell-cell and cell-extracellular matrix (ECM) adhesion. Upon ligand binding, integrins activate signal transduction pathways that mediate cellular signals such as regulation of the cell cycle, ...

s are considered to be the main receptors for hantaviruses ''in vitro'', but complement decay-accelerating factor (DAF) and globular heads of complement C1q receptor (gC1qR) have mediated attachment in cultured cells too. Entry may proceed through a number of possible routes, including

clathrin Clathrin is a protein that plays a major role in the formation of coated vesicles. Clathrin was first isolated and named by Barbara Pearse in 1976. It forms a triskelion shape composed of three clathrin heavy chains and three light chains. Whe ...

-dependent

endocytosis Endocytosis is a cellular process in which substances are brought into the cell. The material to be internalized is surrounded by an area of cell membrane, which then buds off inside the cell to form a vesicle containing the ingested material. E ...

, clathrin-independent receptor-mediated endocytosis, and micro

pinocytosis In cellular biology, pinocytosis, otherwise known as fluid endocytosis and bulk-phase pinocytosis, is a mode of endocytosis in which small molecules dissolved in extracellular fluid are brought into the cell through an invagination of the cell me ...

. Viral particles are then transported to late

endosome Endosomes are a collection of intracellular sorting organelles in eukaryotic cells. They are parts of endocytic membrane transport pathway originating from the trans Golgi network. Molecules or ligands internalized from the plasma membrane can ...

s. Gc-mediated membrane fusion with the endosomal membrane, triggered by low pH, releases the nucleocapsid into the

cytoplasm In cell biology, the cytoplasm is all of the material within a eukaryotic cell, enclosed by the cell membrane, except for the cell nucleus. The material inside the nucleus and contained within the nuclear membrane is termed the nucleoplasm. The ...

. After the release of the nucleocapsids into cytoplasm, the complexes are targeted to the endoplasmic reticulum–Golgi intermediate compartments (ERGIC) through microtubular-associated movement resulting in the formation of viral factories at ERGIC. These factories then facilitate transcription and subsequent translation of the viral proteins. Transcription of viral genes must be initiated by association of the L protein with the three nucleocapsid species. In addition to transcriptase and replicase functions, the viral L protein is also thought to have an endonuclease activity that cleaves cellular messenger RNAs (mRNAs) for the production of capped primers used to initiate transcription of viral mRNAs. As a result of this

cap snatching The first step of transcription for some negative, single-stranded RNA viruses is cap snatching, in which the first 10 to 20 residues of a host cell RNA are removed (snatched) and used as the 5′ cap and primer to initiate the synthesis of the na ...

, the mRNAs of hantaviruses are capped and contain nontemplated 5'-terminal extensions. The G1 (or Gn) and G2 (Gc) glycoproteins form hetero-oligomers and are then transported from the

endoplasmic reticulum The endoplasmic reticulum (ER) is, in essence, the transportation system of the eukaryotic cell, and has many other important functions such as protein folding. It is a type of organelle made up of two subunits – rough endoplasmic reticulum ( ...

to the

Golgi complex The Golgi apparatus (), also known as the Golgi complex, Golgi body, or simply the Golgi, is an organelle found in most eukaryotic cells. Part of the endomembrane system in the cytoplasm, it packages proteins into membrane-bound vesicles insi ...

, where

glycosylation Glycosylation is the reaction in which a carbohydrate (or ' glycan'), i.e. a glycosyl donor, is attached to a hydroxyl or other functional group of another molecule (a glycosyl acceptor) in order to form a glycoconjugate. In biology (but not al ...

is completed. The L protein produces nascent genomes by replication via a positive-sense RNA intermediate. Hantavirus virions are believed to assemble by association of nucleocapsids with glycoproteins embedded in the membranes of the Golgi, followed by budding into the Golgi cisternae. Nascent virions are then transported in secretory

vesicles Vesicle may refer to: ; In cellular biology or chemistry * Vesicle (biology and chemistry), a supramolecular assembly of lipid molecules, like a cell membrane * Synaptic vesicle ; In human embryology * Vesicle (embryology), bulge-like features o ...

to the

plasma membrane The cell membrane (also known as the plasma membrane (PM) or cytoplasmic membrane, and historically referred to as the plasmalemma) is a biological membrane that separates and protects the interior of all cells from the outside environment (t ...

and released by

exocytosis Exocytosis () is a form of active transport and bulk transport in which a cell transports molecules (e.g., neurotransmitters and proteins) out of the cell ('' exo-'' + ''cytosis''). As an active transport mechanism, exocytosis requires the use o ...

Pathogenesis

The

pathogenesis Pathogenesis is the process by which a disease or disorder develops. It can include factors which contribute not only to the onset of the disease or disorder, but also to its progression and maintenance. The word comes from Greek πάθος ''pat ...

of hantavirus infections is unclear as there is a lack of animal models to describe it (rats and mice do not seem to acquire severe disease). While the primary site of viral replication in the body is not known, in HFRS the main effect is in the blood vessels while in HPS most symptoms are associated with the lungs. In HFRS, there are increased vascular permeability and decreased blood pressure due to endothelial dysfunction and the most dramatic damage is seen in the kidneys, whereas in HPS, the lungs, spleen, and gall bladder are most affected. Early symptoms of HPS tend to present similarly to the

flu Influenza, commonly known as "the 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 symptom ...

(muscle aches, fever and fatigue) and usually appear around 2 to 3 weeks after exposure. Later stages of the disease (about 4 to 10 days after symptoms start) include difficulty breathing, shortness of breath and coughing.

Evolution

Findings of significant congruence between phylogenies of hantaviruses and phylogenies of their rodent reservoirs have led to the theory that rodents, although infected by the virus, are not harmed by it because of long-standing hantavirus–rodent host

coevolution In biology, coevolution occurs when two or more species reciprocally affect each other's evolution through the process of natural selection. The term sometimes is used for two traits in the same species affecting each other's evolution, as well ...

, although findings in 2008 led to new hypotheses regarding hantavirus evolution. Various hantaviruses have been found to infect multiple rodent species, and cases of cross-species transmission (

host switch In parasitology and epidemiology, a host switch (or host shift) is an evolutionary change of the host specificity of a parasite or pathogen. For example, the human immunodeficiency virus used to infect and circulate in non-human primates in West- ...

ing) have been recorded. Additionally, rates of substitution based on nucleotide sequence data reveal that hantavirus clades and rodent subfamilies may not have diverged at the same time. Furthermore, as of 2007 hantaviruses have been found in multiple species of non-rodent shrews and moles. Taking into account the inconsistencies in the theory of coevolution, it was proposed in 2009 that the patterns seen in hantaviruses in relation to their reservoirs could be attributed to preferential host switching directed by geographical proximity and adaptation to specific host types. Another proposal from 2010 is that geographical clustering of hantavirus sequences may have been caused by an isolation-by-distance mechanism. Upon comparison of the hantaviruses found in hosts of orders

Rodent Rodents (from Latin , 'to gnaw') are mammals of the order Rodentia (), which are characterized by a single pair of continuously growing incisors in each of the upper and lower jaws. About 40% of all mammal species are rodents. They are na ...

ia and

Eulipotyphla Eulipotyphla (, which means "truly fat and blind") is an order of mammals suggested by molecular methods of phylogenetic reconstruction, which includes the laurasiatherian members of the now-invalid polyphyletic order Lipotyphla, but not the afr ...

, it was proposed in 2011 that the hantavirus evolutionary history is a mix of both host switching and codivergence and that ancestral shrews or moles, rather than rodents, may have been the early original hosts of ancient hantaviruses. A

Bayesian Thomas Bayes (/beɪz/; c. 1701 – 1761) was an English statistician, philosopher, and Presbyterian minister. Bayesian () refers either to a range of concepts and approaches that relate to statistical methods based on Bayes' theorem, or a followe ...

analysis in 2014 suggested a common origin for these viruses ~2000 years ago. The association with particular rodent families appears to have been more recent. The viruses carried by the subfamilies

Arvicolinae The Arvicolinae are a subfamily of rodents that includes the voles, lemmings, and muskrats. They are most closely related to the other subfamilies in the Cricetidae (comprising the hamsters and New World rats and mice). Some authorities place ...

and

Murinae The Old World rats and mice, part of the subfamily Murinae in the family Muridae, comprise at least 519 species. Members of this subfamily are called murines. In terms of species richness, this subfamily is larger than all mammal families excep ...

originated in

Asia Asia (, ) is one of the world's most notable geographical regions, which is either considered a continent in its own right or a subcontinent of Eurasia, which shares the continental landmass of Afro-Eurasia with Africa. Asia covers an area ...

500–700 years ago. These subsequently spread to

Africa Africa is the world's second-largest and second-most populous continent, after Asia in both cases. At about 30.3 million km2 (11.7 million square miles) including adjacent islands, it covers 6% of Earth's total surface area ...

Europe Europe is a large peninsula conventionally considered a continent in its own right because of its great physical size and the weight of its history and traditions. Europe is also considered a Continent#Subcontinents, subcontinent of Eurasia ...

, North America and

Siberia Siberia ( ; rus, Сибирь, r=Sibir', p=sʲɪˈbʲirʲ, a=Ru-Сибирь.ogg) is an extensive geographical region, constituting all of North Asia, from the Ural Mountains in the west to the Pacific Ocean in the east. It has been a part of ...

possibly carried by their hosts. The species infecting the subfamily

Neotominae The Neotominae are a subfamily of the family Cricetidae. They consist of four tribes, 16 genera, and many species of New World rats and mice, predominantly found in North America. Among them are the well-known deer mice, white-footed mice, packra ...

evolved 500–600 years ago in Central America and then spread toward North America. The species infecting

Sigmodontinae The rodent subfamily Sigmodontinae includes New World rats and mice, with at least 376 species. Many authorities include the Neotominae and Tylomyinae as part of a larger definition of Sigmodontinae. When those genera are included, the specie ...

evolved in

Brazil Brazil ( pt, Brasil; ), officially the Federative Republic of Brazil (Portuguese: ), is the largest country in both South America and Latin America. At and with over 217 million people, Brazil is the world's fifth-largest country by area ...

400 years ago. Their ancestors may have been a Neotominae-associated virus from northern South America. The evolution of

shrew Shrews (family Soricidae) are small mole-like mammals classified in the order Eulipotyphla. True shrews are not to be confused with treeshrews, otter shrews, elephant shrews, West Indies shrews, or marsupial shrews, which belong to different fa ...

-borne hantaviruses appears to have involved natural occurrences of

homologous recombination Homologous recombination is a type of genetic recombination in which genetic information is exchanged between two similar or identical molecules of double-stranded or single-stranded nucleic acids (usually DNA as in cellular organisms but may ...

events and the reassortment of

genome In the fields of molecular biology and genetics, a genome is all the genetic information of an organism. It consists of nucleotide sequences of DNA (or RNA in RNA viruses). The nuclear genome includes protein-coding genes and non-coding ge ...

segments. The evolution of Tula orthohantavirus carried by the European

common vole The common vole (''Microtus arvalis'') is a European rodent. Distribution and habitat The common vole is hardly restricted in means of distribution and habitat and inhabits large areas of Eurasia but, apart from the Orkney vole, not the Bri ...

also appears to have involved

events.

Taxonomy

Orthohantaviruses belong to the family ''

'' and members of both the genus and the family are called hantaviruses. The genus also belongs to the subfamily '' Mammantavirinae'', the

mammal Mammals () are a group of vertebrate animals constituting the class Mammalia (), characterized by the presence of mammary glands which in females produce milk for feeding (nursing) their young, a neocortex (a region of the brain), fur or ...

ian hantaviruses, with three other genera. Orthohantaviruses specifically are mammalian hantaviruses that are transmitted among rodents. The genus contains these 38 species: * '' Andes orthohantavirus'' * '' Asama orthohantavirus'' * '' Asikkala orthohantavirus'' * '' Bayou orthohantavirus'' * '' Black Creek Canal orthohantavirus'' * '' Bowe orthohantavirus'' * '' Bruges orthohantavirus'' * '' Cano Delgadito orthohantavirus'' * '' Cao Bang orthohantavirus'' * '' Choclo orthohantavirus'' * '' Dabieshan orthohantavirus'' * ''

Dobrava-Belgrade orthohantavirus ''Dobrava-Belgrade orthohantavirus'' (DOBV), also known as Dobrava virus, is an enveloped, single-stranded, negative-sense RNA virus species of Old World ''Orthohantavirus''. It is one of several species of Hantavirus that is the causative agent ...

'' * '' El Moro Canyon orthohantavirus'' * '' Fugong orthohantavirus'' * '' Fusong orthohantavirus'' * ''

Hantaan orthohantavirus ''Hantaan orthohantavirus'' (HTNV) is an enveloped, single-stranded, negative-sense RNA virus species of Old World ''Orthohantavirus''. It is the causative agent of Korean hemorrhagic fever in humans. It is named for the Hantan River in South ...

'' * ''

Jeju orthohantavirus Jeju may refer to: * Jeju Island (Jejudo), an island near South Korea * Jeju Province (formerly transliterated Cheju), a province of South Korea comprising Jejudo **Jeju City, the biggest city on Jejudo **Jeju dog, a dog native to Jejudo **Jeju la ...

'' * '' Kenkeme orthohantavirus'' * '' Khabarovsk orthohantavirus'' * '' Laguna Negra orthohantavirus'' * '' Luxi orthohantavirus'' * '' Maporal orthohantavirus'' * '' Montano orthohantavirus'' * '' Necocli orthohantavirus'' * '' Oxbow orthohantavirus'' * ''

'' * '' Puumala orthohantavirus'' * ''

Robina orthohantavirus Robina may refer to: People * Robina Courtin (born 1944), Buddhist nun * Robina Higgins (1915–1990), athlete * Robina Muqimyar (born 1986), athlete * Robina Qureshi (born 1964), human rights campaigner * Robina Suwol, Children's Environmental ...

'' * '' Rockport orthohantavirus'' * '' Sangassou orthohantavirus'' * '' Seewis orhtohantavirus'' * '' Seoul orthohantavirus'' * ''

Sin Nombre orthohantavirus ''Sin Nombre orthohantavirus'' (SNV) (from Spanish, meaning "without a name") is the prototypical etiologic agent of hantavirus cardiopulmonary syndrome (HCPS). Discovered in 1993 near the Cañon de la Muerte on the Navajo Reservation, it was ...

'' * '' Tatenale orthohantavirus'' * '' Thailand orthohantavirus'' * '' Tigray orthohantavirus'' * '' Tula orthohantavirus'' * '' Yakeshi orthohantavirus'' Hantaviruses that were formerly classified as species in this genus and which were not reassigned as member viruses of any existing species include: * ''Isla Vista hantavirus'', also called Isla Vista virus * ''Muleshoe hantavirus'', also called Muleshoe virus * ''Rio Segundo hantavirus'', also called Rio Segundo virus

Prevention

According to the U.S. CDC, the best prevention against contracting hantavirus is to eliminate or minimize contact with rodents in the home, workplace, or campsite. As the virus can be transmitted by rodent saliva, excretions, and bites, control of rats and mice in areas frequented by humans is key for disease prevention. General prevention can be accomplished by disposing of rodent nests, sealing any cracks and holes in homes where mice or rats could enter, setting traps, or laying down poisons or using natural predators such as cats in the home. The duration that hantaviruses remain infectious in the environment varies based on factors such as the rodent's diet, temperature, humidity, and whether indoors or outdoors. The viruses have been demonstrated to remain active for 2–3 days at normal room temperature, while ultraviolet rays in direct sunlight kill them within a few hours. Rodent droppings or urine of indeterminate age, though, should always be treated as infectious.

Vaccine

, no vaccines against hantaviruses have been approved by the U.S. FDA, but whole virus inactivated bivalent vaccines against Hantaan virus and Seoul virus are available in China and South Korea. In both countries, the use of the vaccine, combined with other preventive measures, has significantly reduced the incidence of hantavirus infections. Apart from these vaccines, four types of vaccines have been researched: DNA vaccines targeting the M genome segment and the S genome segment, subunit vaccines that use recombinant Gn, Gc, and N proteins of the virus, virus vector vaccines that have recombinant hantavirus proteins inserted in them, and virus-like particle vaccines that contain viral proteins, but lack genetic material. Of these, only DNA vaccines have entered into clinical trials.

Treatment

Ribavirin may be a drug for HPS and HFRS, but its effectiveness remains unknown; still, spontaneous recovery is possible with supportive treatment. People with suspected hantavirus infection may be admitted to a hospital, and given oxygen and mechanical ventilation support to help them breathe during the acute pulmonary stage with severe respiratory distress. Immunotherapy, administration of human neutralizing antibodies during acute phases of hantavirus, has been studied only in mice, hamsters, and rats. No controlled clinical trials have been reported.

Epidemiology

Hantavirus infections have been reported from all continents except Australia. Regions especially affected by HFRS include

China China, officially the People's Republic of China (PRC), is a country in East Asia. It is the world's most populous country, with a population exceeding 1.4 billion, slightly ahead of India. China spans the equivalent of five time zones and ...

, the

Korean Peninsula Korea ( ko, 한국, or , ) is a peninsular region in East Asia. Since 1945, it has been divided at or near the 38th parallel, with North Korea (Democratic People's Republic of Korea) comprising its northern half and South Korea (Republic o ...

Russia Russia (, , ), or the Russian Federation, is a List of transcontinental countries, transcontinental country spanning Eastern Europe and North Asia, Northern Asia. It is the List of countries and dependencies by area, largest country in the ...

(Hantaan, Puumala, and Seoul viruses), and Northern and Western

(

Puumala , area_footnotes = , area_total_km2 = , area_land_km2 = , area_water_km2 = , area_rank = , population_as_of = , population_footnotes = , population_total = , population_density_km2 = , population_rank = , demographics_type1 = , demograph ...

and Dobrava virus). Regions with the highest incidences of hantavirus pulmonary syndrome include

Argentina Argentina (), officially the Argentine Republic ( es, link=no, República Argentina), is a country in the southern half of South America. Argentina covers an area of , making it the second-largest country in South America after Brazil, th ...

Chile Chile, officially the Republic of Chile, is a country in the western part of South America. It is the southernmost country in the world, and the closest to Antarctica, occupying a long and narrow strip of land between the Andes to the east a ...

, the

United States The United States of America (U.S.A. or USA), commonly known as the United States (U.S. or US) or America, is a country primarily located in North America. It consists of 50 states, a federal district, five major unincorporated territorie ...

Canada Canada is a country in North America. Its ten provinces and three territories extend from the Atlantic Ocean to the Pacific Ocean and northward into the Arctic Ocean, covering over , making it the world's second-largest country by tot ...

, and

Panama Panama ( , ; es, link=no, Panamá ), officially the Republic of Panama ( es, República de Panamá), is a transcontinental country spanning the southern part of North America and the northern part of South America. It is bordered by Cos ...

Africa

In 2010, a novel hantavirus,

Sangassou virus ''Sangassou orthohantavirus'' (SANGV) is single-stranded, negative-sense RNA virus species of the genus ''Orthohantavirus'' in the ''Bunyavirales'' order. It was first isolated in an African wood mouse ('' Hylomyscus simus'') in the forest in Gu ...

, was isolated in Africa, which causes HFRS.

Asia

In China, Hong Kong, the Korean Peninsula, and Russia, HFRS is caused by Hantaan, Puumala, and Seoul viruses.

China

In March 2020, a man from

Yunnan Yunnan , () is a landlocked Provinces of China, province in Southwest China, the southwest of the People's Republic of China. The province spans approximately and has a population of 48.3 million (as of 2018). The capital of the province is ...

tested positive for hantavirus. He died while travelling to

Shandong Shandong ( , ; ; alternately romanized as Shantung) is a coastal province of the People's Republic of China and is part of the East China region. Shandong has played a major role in Chinese history since the beginning of Chinese civilizati ...

for work on a chartered bus. According to the ''

Global Times The ''Global Times'' () is a daily tabloid newspaper under the auspices of the Chinese Communist Party's flagship newspaper, the ''People's Daily'', commenting on international issues from a Chinese ultra-nationalistic perspective. The publi ...

'' reports, around 32 other people have been tested for the virus.

Australia

, no human infections have been reported in Australia, though rodents were found to carry antibodies.

Europe

In Europe, two hantaviruses – ''Puumala'' and ''Dobrava-Belgrade'' viruses – are known to cause HFRS. ''Puumala'' usually causes a generally mild disease, nephropathia epidemica, which typically presents with fever, headache, gastrointestinal symptoms, impaired renal function, and blurred vision. ''Dobrava'' infections are similar, except that they often also have hemorrhagic complications. ''Puumala'' virus is carried by its rodent host, the

bank vole The bank vole (''Myodes glareolus'') is a small vole with red-brown fur and some grey patches, with a tail about half as long as its body. A rodent, it lives in woodland areas and is around in length. The bank vole is found in much of Europe an ...

(''Clethrionomys glareolus''), and is present throughout most of Europe, except for the Mediterranean region. Four ''Dobrava'' virus genotypes are known, each carried by a different rodent species. Genotype ''Dobrava'' is found in the

yellow-necked mouse The yellow-necked mouse (''Apodemus flavicollis''), also called yellow-necked field mouse, yellow-necked wood mouse, and South China field mouse, is closely related to the wood mouse, with which it was long confused. It was only recognised as a ...

(''Apodemus flavicollis''), genotypes ''Saaremaa'' and ''Kurkino'' in the

striped field mouse The striped field mouse (''Apodemus agrarius'') is a rodent in the family Muridae. The range of this species stretches from Eastern Europe to Eastern Asia. Synonyms Accepted synonyms include ''Apodemus albostriatus'' (Bechstein, 1801), ''Apode ...

(''Apodemus agrarius''), and genotype ''Sochi'' in the Black Sea field mouse (''Apodemus ponticus''). In 2017 alone, the Robert Koch Institute (RKI) in Germany received 1,713 notifications of hantavirus infections.

North America

Canada

The primary cause of the disease in Canada is Sin Nombre virus-infected deer mice. Between 1989 and 2014, 109 confirmed cases were reported, with the death rate estimated at 29%. The virus exists in deer mice nationwide, but cases were concentrated in western Canada (British Columbia, Alberta, Saskatchewan, and Manitoba) with only one case in eastern Canada. In Canada, " l cases occurred in rural settings and approximately 70% of the cases have been associated with domestic and farming activities."

United States

In the United States, minor cases of HPS include

, New York orthohantavirus, Bayou orthohantavirus, and possibly Black Creek Canal orthohantavirus. , 728 cases of hantavirus had been reported in the United States cumulatively since 1995, across 36 states, not including cases with presumed exposure outside the United States. More than 96% of cases have occurred in states west of the

Mississippi River The Mississippi River is the second-longest river and chief river of the second-largest drainage system in North America, second only to the Hudson Bay drainage system. From its traditional source of Lake Itasca in northern Minnesota, it f ...

. The top 10 states by number of cases ''reported'' (which differs slightly from a count ordered by the state of original ''exposure'') were

New Mexico ) , population_demonym = New Mexican ( es, Neomexicano, Neomejicano, Nuevo Mexicano) , seat = Santa Fe , LargestCity = Albuquerque , LargestMetro = Tiguex , OfficialLang = None , Languages = English, Spanish ( New Mexican), Navajo, Ker ...

(109),

Colorado Colorado (, other variants) is a state in the Mountain West subregion of the Western United States. It encompasses most of the Southern Rocky Mountains, as well as the northeastern portion of the Colorado Plateau and the western edge of t ...

(104),

Arizona Arizona ( ; nv, Hoozdo Hahoodzo ; ood, Alĭ ṣonak ) is a state in the Southwestern United States. It is the 6th largest and the 14th most populous of the 50 states. Its capital and largest city is Phoenix. Arizona is part of the Fou ...

(78),

California California is a U.S. state, state in the Western United States, located along the West Coast of the United States, Pacific Coast. With nearly 39.2million residents across a total area of approximately , it is the List of states and territori ...

(61),

Washington Washington commonly refers to: * Washington (state), United States * Washington, D.C., the capital of the United States ** A metonym for the federal government of the United States ** Washington metropolitan area, the metropolitan area centered o ...

(50),

Texas Texas (, ; Spanish language, Spanish: ''Texas'', ''Tejas'') is a state in the South Central United States, South Central region of the United States. At 268,596 square miles (695,662 km2), and with more than 29.1 million residents in 2 ...

(45),

Montana Montana () is a state in the Mountain West division of the Western United States. It is bordered by Idaho to the west, North Dakota and South Dakota to the east, Wyoming to the south, and the Canadian provinces of Alberta, British Columbi ...

(43),

Utah Utah ( , ) is a state in the Mountain West subregion of the Western United States. Utah is a landlocked U.S. state bordered to its east by Colorado, to its northeast by Wyoming, to its north by Idaho, to its south by Arizona, and to it ...

(38),

Idaho Idaho ( ) is a state in the Pacific Northwest region of the Western United States. To the north, it shares a small portion of the Canada–United States border with the province of British Columbia. It borders the states of Montana and Wyom ...

(21), and

Oregon Oregon () is a U.S. state, state in the Pacific Northwest region of the Western United States. The Columbia River delineates much of Oregon's northern boundary with Washington (state), Washington, while the Snake River delineates much of it ...

(21); 36% of the total reported cases have resulted in death.

Mexico

In Mexico, rodents have been found to carry hantaviruses include Thomas's giant deer mouse ''(Megadontomys thomasi)'', the

pack rat A pack rat or packrat, also called a woodrat or trade rat, are any species in the North and Central American rodent genus ''Neotoma''. Pack rats have a rat-like appearance, with long tails, large ears, and large, black eyes. Pack rats are notice ...

''Neotoma picta'',

Orizaba deer mouse The Orizaba deer mouse (''Peromyscus beatae'') is a small species of rodent in the family Cricetidae, native to El Salvador, Guatemala, Honduras, and Mexico Mexico (Spanish: México), officially the United Mexican States, is a country i ...

''(Peromyscus beatae)'',

Western harvest mouse The western harvest mouse (''Reithrodontomys megalotis'') is a small neotomine mouse native to most of the western United States. Many authorities consider the endangered salt marsh harvest mouse to be a subspecies, but the two are now usually ...

''(Reithrodontomys megalotis)'' and Sumichrast's harvest mouse ''(Reithrodontomys sumichrasti)''.

South America

Agents of HPS found in

South America South America is a continent entirely in the Western Hemisphere and mostly in the Southern Hemisphere, with a relatively small portion in the Northern Hemisphere at the northern tip of the continent. It can also be described as the southe ...

include the

(also called Oran, Castelo de Sonhos – Portuguese for "Castle of Dreams", Lechiguanas, Juquitiba, Araraquara, and Bermejo virus, among many other synonyms), which is the only hantavirus that has shown an interpersonal form of transmission, and the Laguna Negra virus, an extremely close relative of the previously known Rio Mamore virus. Rodents that have been shown to carry hantaviruses include ''

Abrothrix longipilis ''Abrothrix longipilis'', also known as the long-haired grass mouse or long-haired akodont,Musser and Carleton, 2005, p. 1089 is a species of rodent in the family Cricetidae. It is found in central and southern Argentina and Chile. The south ...

'' and ''

Oligoryzomys longicaudatus ''Oligoryzomys longicaudatus'', also known as the long-tailed colilargo or long-tailed pygmy rice rat, is a species of rodent in the genus '' Oligoryzomys'' of the family Cricetidae. It is found in the southern Andes of Chile and Argentina, with ...

''.

History

Hantavirus HFRS was likely first referenced in China in the 12th century. The first clinical recognition was in 1931 in northeast China. Around the same time in the 1930s, NE was identified in Sweden. HFRS came to the recognition of western physicians during the

Korean War , date = {{Ubl, 25 June 1950 – 27 July 1953 (''de facto'')({{Age in years, months, weeks and days, month1=6, day1=25, year1=1950, month2=7, day2=27, year2=1953), 25 June 1950 – present (''de jure'')({{Age in years, months, weeks a ...

between 1951 and 1954 when more than 3,000

United Nations The United Nations (UN) is an intergovernmental organization whose stated purposes are to maintain international peace and international security, security, develop friendly relations among nations, achieve international cooperation, and be ...

soldiers fell ill in an outbreak. In 1976, the first pathogenic hantavirus, the ''

'', was isolated from rodents near the

. Other prominent hantaviruses that cause HFRS, including the ''

'', '' Puumala orthohantavirus'', and '' Seoul orthohantavirus'', were identified in the years after then and are collectively referred to as the Old World hantaviruses. In 1993, an outbreak of HCPS, then unrecognized, occurred in the

Four Corners The Four Corners is a region of the Southwestern United States consisting of the southwestern corner of Colorado, southeastern corner of Utah, northeastern corner of Arizona, and northwestern corner of New Mexico. The Four Corners area ...

region of the United States and led to the discovery of the ''

''. Since then, approximately 43 hantavirus strains, of which 20 are pathogenic, have been found in the Americas and are referred to as the New World hantaviruses. This includes the '' Andes orthohantavirus'', one of the primary causes of HCPS in South America and the only hantavirus known to be capable of person-to-person transmission. In late

medieval England England in the Middle Ages concerns the history of England during the medieval period, from the end of the 5th century through to the start of the Early Modern period in 1485. When England emerged from the collapse of the Roman Empire, the econ ...

a mysterious

sweating sickness Sweating sickness, also known as the sweats, English sweating sickness, English sweat or ''sudor anglicus'' in Latin, was a mysterious and contagious disease that struck England and later continental Europe in a series of epidemics beginning ...

swept through the country in 1485 just before the

Battle of Bosworth Field The Battle of Bosworth or Bosworth Field was the last significant battle of the Wars of the Roses, the civil war between the houses of Lancaster and York that extended across England in the latter half of the 15th century. Fought on 22 Augu ...

. Noting that the symptoms overlap with hantavirus pulmonary syndrome, several scientists have theorized that the virus may have been the cause of the disease. The hypothesis was criticized because sweating sickness was recorded as being transmitted from human to human, whereas hantaviruses were not known to spread in this way.

References

External links

"Hantaviruses, with emphasis on Four Corners Hantavirus"
by Brian Hjelle, M.D., Department of Pathology, School of Medicine, University of New Mexico
CDC's Hantavirus Fact Sheet (PDF)

Virus Pathogen Database and Analysis Resource (ViPR): Hantaviridae

{{Authority control Hantaviridae Hemorrhagic fevers Rodent-carried diseases Viral diseases Virus genera