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''Orthohantavirus'' is a genus of single-stranded, enveloped, negative-sense
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 viruse ...
es in the family '' Hantaviridae'' 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 ''Bunyavi ...
''. 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 ...
in
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 ...
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 (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 Nombr ...
(HPS), also known as hantavirus cardiopulmonary syndrome (HCPS), while others have not been associated with known human disease (e.g. Prospect Hill virus). 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 was reported in South America. Orthohantaviruses are named for the Greek word ''ortho''- meaning "straight" or "true" and for the Hantan River in
South Korea South Korea, officially the Republic of Korea (ROK), is a country in East Asia, constituting the southern part of the Korean Peninsula and sharing a land border with North Korea. Its western border is formed by the Yellow Sea, while its eas ...
, where the first member species ( Hantaan virus) was identified and isolated in 1976 by Ho Wang Lee.


Disease

Hantavirus infections in humans are associated with two diseases: hemorrhagic fever with renal syndrome (HFRS) and
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 Nombr ...
(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 dia ...
, thrombocytopenia, 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 parasit ...
. 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''.


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 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 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 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. Death from cardiovascular shock 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 of fine solid particles or liquid droplets in air or another gas. Aerosols can be natural or anthropogenic. Examples of natural aerosols are fog or mist, dust, forest exudates, and geyser steam. Examples of anthropo ...
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 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'' has ...
) 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 ma ...
(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 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 used for transcription and replication. Within virions, 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 biomolecule ...
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 facilitated by binding with the viral nucleocapsid (N) protein. The large segment is 6530–6550 nucleotides (nt) in length, the medium is 3613–3707 nt in length and the small is 1696–2083 nt in length. No nonstructural proteins are known, unlike the other genera in this family. At the 5' and 3' of each segment are short noncoding sequences: the noncoding segment in all sequences at the 5' end is 37–51 nt. The 3' noncoding regions differ: L segment 38–43 nt; M segment 168–229 nt; and S segment 370–730 nt. The 3' end of the S segment is conserved between the genera suggesting a functional role.


Lifecycle

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 and introduces viral material into the cell. The major steps involved in viral entry are shown below. Despite the variat ...
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, 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 ...
. 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. T ...
. 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 ...
, 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, where glycosylation 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 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 ( ...
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 ...
.


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 ''p ...
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 Wes ...
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 ...
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 af ...
, 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 follower ...
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, 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 o ...
possibly carried by their hosts. The species infecting the subfamily Neotominae 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 spec ...
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-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 be ...
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 ...
segments. The evolution of Tula orthohantavirus carried by the European common vole also appears to have involved
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 be ...
events.


Taxonomy

Orthohantaviruses belong to the family '' Hantaviridae'' 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), fu ...
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 ''Black Creek Canal orthohantavirus'' (BCCV) is a single-stranded, negative sense RNA virus species of New World '' Orthohantavirus''. It was first isolated in cotton rats (''Sigmodon hispidus'') found in the Black Creek Canal area of Dade Cou ...
'' * '' Bowe orthohantavirus'' * '' Bruges orthohantavirus'' * '' Cano Delgadito orthohantavirus'' * '' Cao Bang orthohantavirus'' * '' Choclo orthohantavirus'' * '' Dabieshan orthohantavirus'' * '' Dobrava-Belgrade orthohantavirus'' * '' El Moro Canyon orthohantavirus'' * '' Fugong orthohantavirus'' * '' Fusong orthohantavirus'' * '' Hantaan orthohantavirus'' * '' Jeju orthohantavirus'' * '' Kenkeme orthohantavirus'' * '' Khabarovsk orthohantavirus'' * '' Laguna Negra orthohantavirus'' * '' Luxi orthohantavirus'' * '' Maporal orthohantavirus'' * '' Montano orthohantavirus'' * '' Necocli orthohantavirus'' * '' Oxbow orthohantavirus'' * '' Prospect Hill orthohantavirus'' * '' Puumala orthohantavirus'' * '' Robina orthohantavirus'' * '' 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 List of countries and dependencies by population, most populous country, with a Population of China, population exceeding 1.4 billion, slig ...
, 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 ...
, Russia (Hantaan, Puumala, and Seoul viruses), and Northern and Western Europe ( Puumala 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 ...
,
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 ...
, 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 territo ...
,
Canada Canada is a country in North America. Its Provinces and territories of Canada, 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 ...
, and
Panama Panama ( , ; es, link=no, Panamá ), officially the Republic of Panama ( es, República de Panamá), is a List of transcontinental countries#North America and South America, transcontinental country spanning the Central America, southern ...
.


Africa

In 2010, a novel hantavirus, Sangassou virus, 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 province in 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 Kunming. The province borders the ...
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 (''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), ''Apodemu ...
(''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
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 ...
, New York orthohantavirus, Bayou orthohantavirus, and possibly
Black Creek Canal orthohantavirus ''Black Creek Canal orthohantavirus'' (BCCV) is a single-stranded, negative sense RNA virus species of New World '' Orthohantavirus''. It was first isolated in cotton rats (''Sigmodon hispidus'') found in the Black Creek Canal area of Dade Cou ...
. , 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, ...
. 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, ...
(109),
Colorado Colorado (, other variants) is a state in the Mountain states, 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 wes ...
(104),
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(78),
California California is a state in the Western United States, located along the Pacific Coast. With nearly 39.2million residents across a total area of approximately , it is the most populous U.S. state and the 3rd largest by area. It is also the mo ...
(61), Washington (50),
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(43),
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(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 in ...
''(Peromyscus beatae)'', Western harvest mouse ''(Reithrodontomys megalotis)'' and Sumichrast's harvest mouse ''(Reithrodontomys sumichrasti)''.


South America

Agents of HPS found in South America include the Andes virus (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'' and '' Oligoryzomys longicaudatus''.


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 {{Infobox military conflict , conflict = Korean War , partof = the Cold War and the Korean conflict , image = Korean War Montage 2.png , image_size = 300px , caption = Clockwise from top:{ ...
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 security, develop friendly relations among nations, achieve international cooperation, and be a centre for harmonizi ...
soldiers fell ill in an outbreak. In 1976, the first pathogenic hantavirus, the '' Hantaan orthohantavirus'', was isolated from rodents near the Hantan River in
South Korea South Korea, officially the Republic of Korea (ROK), is a country in East Asia, constituting the southern part of the Korean Peninsula and sharing a land border with North Korea. Its western border is formed by the Yellow Sea, while its eas ...
. Other prominent hantaviruses that cause HFRS, including the '' Dobrava-Belgrade orthohantavirus'', '' 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 region of the United States and led to the discovery of the ''
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 ...
''. 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 ec ...
a mysterious sweating sickness 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 Aug ...
. 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.


See also

*
1993 Four Corners hantavirus outbreak The 1993 Four Corners hantavirus outbreak was an outbreak of hantavirus that caused the first known human cases of hantavirus disease in the United States. It occurred within the Four Corners region – the geographic intersection of the U.S. stat ...
* Bat-borne virus *
Cocoliztli epidemics The Cocoliztli Epidemic or the Great Pestilence was an outbreak of a mysterious illness characterized by high fevers and bleeding which caused millions of deaths in New Spain during the 16th-century. The Aztec people called it ''cocoliztli'', Nah ...
* Conjunctival suffusion * Limestone Canyon virus *
List of cutaneous conditions Many skin conditions affect the human integumentary system—the organ system covering the entire surface of the body and composed of skin, hair, nails, and related muscle and glands. The major function of this system is as a barrier against ...


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