Hantavirus

Hantavirus

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Hantaviruses are negative sense RNA virus
RNA virus
An RNA virus is a virus that has RNA as its genetic material. This nucleic acid is usually single-stranded RNA but may be double-stranded RNA...

es in the Bunyaviridae
Bunyaviridae
Bunyaviridae is a family of negative-stranded RNA viruses. Though generally found in arthropods or rodents, certain viruses in this family occasionally infect humans. Some of them also infect plants....

family. Humans may be infected with hantaviruses through rodent
Rodent
Rodentia is an order of mammals also known as rodents, characterised by two continuously growing incisors in the upper and lower jaws which must be kept short by gnawing....

 bites, urine, saliva or contact with rodent waste products. Some hantaviruses cause potentially fatal diseases in humans, hemorrhagic fever with renal syndrome (HFRS) and hantavirus pulmonary syndrome (HPS), but others have not been associated with human disease. Human infections of hantaviruses have almost entirely been linked to human contact with rodent excrement, but recent human-to-human transmission has been reported with the Andes virus in South America. The name hantavirus is derived from the Hantan River
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-water rafting....

 area in South Korea
South Korea
The Republic of Korea , , is a sovereign state in East Asia, located on the southern portion of the Korean Peninsula. It is neighbored by the People's Republic of China to the west, Japan to the east, North Korea to the north, and the East China Sea and Republic of China to the south...

, which provided the founding member of the group: Hantaan virus (HTNV), isolated in the late 1970s by Ho-Wang Lee and colleagues. HTNV is one of several hantaviruses that cause HFRS, formerly known as Korean hemorrhagic fever.

History


The hantaviruses are a relatively newly discovered genus of viruses. Several thousand United Nations soldiers became ill with "Korean haemorrhagic fever" (now called HFRS) during the Korean War
Korean War
The Korean War was a conventional war between South Korea, supported by the United Nations, and North Korea, supported by the People's Republic of China , with military material aid from the Soviet Union...

. This outbreak sparked a 25-year search for the etiologic agent. The isolation of Hantaan virus, or HTNV, was reported by Ho-Wang Lee of South Korea
South Korea
The Republic of Korea , , is a sovereign state in East Asia, located on the southern portion of the Korean Peninsula. It is neighbored by the People's Republic of China to the west, Japan to the east, North Korea to the north, and the East China Sea and Republic of China to the south...

 in 1978.

In 1993, an outbreak of Hantavirus pulmonary syndrome (HPS, see below) occurred in the Four Corners region in the southwestern United States. The viral cause of the disease was found only weeks later and was called the Sin Nombre virus
Sin Nombre virus
The Sin Nombre virus is the prototypical etiologic agent of hantavirus cardiopulmonary syndrome ....

 (SNV, in Spanish
Spanish language
Spanish , also known as Castilian , is a Romance language in the Ibero-Romance group that evolved from several languages and dialects in central-northern Iberia around the 9th century and gradually spread with the expansion of the Kingdom of Castile into central and southern Iberia during the...

, "Virus sin nombre", for "nameless virus"). Its rodent host, Peromyscus maniculatus
Peromyscus maniculatus
Peromyscus maniculatus is a rodent native to North America. It is most commonly called the Deer Mouse, although that name is common to most species of Peromyscus and is fairly widespread across the continent, with the major exception being the southeast United States and the far north.Like other...

, was first identified by Terry Yates
Terry Yates
Terry Lamon Yates was an American biologist and academic who is credited with discovering the source of the hantavirus in the American Southwest in 1993. Yates' specialty as a biologist was the study of rodents and other small mammals....

, a professor at the University of New Mexico
University of New Mexico
The University of New Mexico at Albuquerque is a public research university located in Albuquerque, New Mexico, in the United States. It is the state's flagship research institution...

. In addition to Hantaan virus and Sin Nombre virus, several other hantaviruses have been implicated as etiologic agents for either HFRS or HPS. Other identified hantaviruses have not been associated with disease.

Classification


Hantaviruses are Bunyaviruses. The Bunyaviridae family is divided into five genera: Orthobunyavirus
Orthobunyavirus
Orthobunyavirus is a genus of the Bunyaviridae family.The genus is most diverse in Africa, Australia and Oceania, but occurs almost world-wide...

, Nairovirus
Nairovirus
Nairovirus is a genus in the family Bunyaviridae that include viruses with circular, negative-sense single stranded RNA. It got its name from the Nairobi sheep disease that affects the gastrointestinal tracts of sheep and goats...

, Phlebovirus, Tospovirus
Tospovirus
The Tospoviruses are a genus of negative RNA virus found within the family Bunyaviridae. They are the sole group of plant infecting viruses in this family, as all other described members of the Bunyaviridae infect animals. The genus takes its name from the discovery of Tomato spotted wilt virus ...

, and Hantavirus. Like all members of this family, hantaviruses have genomes comprising three negative-sense, single-stranded RNA segments, and so are classified as negative sense RNA virus
RNA virus
An RNA virus is a virus that has RNA as its genetic material. This nucleic acid is usually single-stranded RNA but may be double-stranded RNA...

es. Members of other Bunyaviridae family genera are generally arthropod
Arthropod
An arthropod is an invertebrate animal having an exoskeleton , a segmented body, and jointed appendages. Arthropods are members of the phylum Arthropoda , and include the insects, arachnids, crustaceans, and others...

-borne viruses, but hantaviruses are thought to be transmitted to humans mainly through inhalation of aerosolized rodent
Rodent
Rodentia is an order of mammals also known as rodents, characterised by two continuously growing incisors in the upper and lower jaws which must be kept short by gnawing....

 excreta or rodent bites.

Genome


Like other members of the bunyavirus family, hantaviruses are enveloped viruses with a genome that consists of three single-stranded, negative sense RNA segments designated S (small), M (medium), and L (large). The S RNA encodes the nucleocapsid (N) protein. The M RNA encodes a polyprotein that is cotranslationally cleaved to yield the envelope glycoprotein
Glycoprotein
Glycoproteins are proteins that contain oligosaccharide chains covalently attached to polypeptide side-chains. The carbohydrate is attached to the protein in a cotranslational or posttranslational modification. This process is known as glycosylation. In proteins that have segments extending...

s Gn (formerly G1) and Gc (formerly G2). The L RNA encodes the L protein, which functions as the viral transcriptase/replicase. 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 Bunyaviridae, each of the three segments has a consensus 39-terminal nucleotide
Nucleotide
Nucleotides are molecules that, when joined together, make up the structural units of RNA and DNA. In addition, nucleotides participate in cellular signaling , and are incorporated into important cofactors of enzymatic reactions...

 sequence (AUCAUCAUC), which is complementary to the 59 terminal sequence and is distinct from those of the other four genera in the family. These sequences may form panhandle structures which seem likely to play a role in replication. 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.

Virions


Hantavirus virions are about 100 nanometre
Nanometre
A nanometre is a unit of length in the metric system, equal to one billionth of a metre. The name combines the SI prefix nano- with the parent unit name metre .The nanometre is often used to express dimensions on the atomic scale: the diameter...

s (nm) in diameter. The lipid bilayer of the viral envelope
Viral envelope
Many viruses have viral envelopes covering their protein capsids. The envelopes typically are derived from portions of the host cell membranes , but include some viral glycoproteins. Functionally, viral envelopes are used to help viruses enter host cells...

 is about five nm thick and is embedded with viral surface proteins to which sugar residues are attached. These glycoproteins, known as G1 and G2, are encoded by the M segment of the viral genome. They tend to associate (heterodimerize) with each other and have both an interior tail and an exterior domain that extends to about six 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
RNA polymerase
RNA polymerase is an enzyme that produces RNA. In cells, RNAP is needed for constructing RNA chains from DNA genes as templates, a process called transcription. RNA polymerase enzymes are essential to life and are found in all organisms and many viruses...

 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 gram per cubic centimeter. These features are common to all members of the Bunyaviridae.

Life cycle


Entry into host cells is thought to occur by attachment of virions to cellular receptors and subsequent endocytosis
Endocytosis
Endocytosis is a process by which cells absorb molecules by engulfing them. It is used by all cells of the body because most substances important to them are large polar molecules that cannot pass through the hydrophobic plasma or cell membrane...

. Nucleocapsids are introduced into the cytoplasm by pH-dependent fusion of the virion with the endosomal membrane. Subsequent to release of the nucleocapsids into cytoplasm, the complexes are targeted to the ER-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 mRNAs of hantaviruses are capped and contain nontemplated 5' terminal extensions. The G1 (aka Gn) and G2 (Gc) glycoproteins form hetero-oligomers and are then transported from the endoplasmic reticulum
Endoplasmic reticulum
The endoplasmic reticulum is an organelle of cells in eukaryotic organisms that forms an interconnected network of tubules, vesicles, and cisternae...

 to the Golgi complex, where glycosylation
Glycosylation
Glycosylation is the reaction in which a carbohydrate, i.e. a glycosyl donor, is attached to a hydroxyl or other functional group of another molecule . In biology glycosylation refers to the enzymatic process that attaches glycans to proteins, lipids, or other organic molecules...

 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 (biology)
A vesicle is a bubble of liquid within another liquid, a supramolecular assembly made up of many different molecules. More technically, a vesicle is a small membrane-enclosed sack that can store or transport substances. Vesicles can form naturally because of the properties of lipid membranes , or...

 to the plasma membrane and released by exocytosis
Exocytosis
Exocytosis , also known as 'The peni-cytosis', is the durable process by which a cell directs the contents of secretory vesicles out of the cell membrane...

.


Pathogenesis


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

Prevalence


Regions especially affected by HFRS include China
China
Chinese civilization may refer to:* China for more general discussion of the country.* Chinese culture* Greater China, the transnational community of ethnic Chinese.* History of China* Sinosphere, the area historically affected by Chinese culture...

, the Korean Peninsula
Korean Peninsula
The Korean Peninsula is a peninsula in East Asia. It extends southwards for about 684 miles from continental Asia into the Pacific Ocean and is surrounded by the Sea of Japan to the south, and the Yellow Sea to the west, the Korea Strait connecting the first two bodies of water.Until the end of...

, Russia
Russia
Russia or , officially known as both Russia and the Russian Federation , is a country in northern Eurasia. It is a federal semi-presidential republic, comprising 83 federal subjects...

 (Hantaan, Puumala and Seoul viruses), and northern and western Europe
Europe
Europe is, by convention, one of the world's seven continents. Comprising the westernmost peninsula of Eurasia, Europe is generally 'divided' from Asia to its east by the watershed divides of the Ural and Caucasus Mountains, the Ural River, the Caspian and Black Seas, and the waterways connecting...

 (Puumala
Puumala virus
Puumala virus is a species of hantavirus. Humans infected with the virus may develop a haemorrhagic fever with renal syndrome known as nephropathia epidemica. Puumala virus HFRS is lethal in a small percentage of cases....

 and Dobrava virus). Regions with the highest incidences of HCPS include Patagonian Argentina
Argentina
Argentina , officially the Argentine Republic , is the second largest country in South America by land area, after Brazil. It is constituted as a federation of 23 provinces and an autonomous city, Buenos Aires...

, Chile
Chile
Chile ,officially the Republic of Chile , is a country in South America occupying a long, narrow coastal strip between the Andes mountains to the east and the Pacific Ocean to the west. It borders Peru to the north, Bolivia to the northeast, Argentina to the east, and the Drake Passage in the far...

, Brazil
Brazil
Brazil , officially the Federative Republic of Brazil , is the largest country in South America. It is the world's fifth largest country, both by geographical area and by population with over 192 million people...

, the United States
United States
The United States of America is a federal constitutional republic comprising fifty states and a federal district...

, Canada
Canada
Canada is a North American country consisting of ten provinces and three territories. Located in the northern part of the continent, it extends from the Atlantic Ocean in the east to the Pacific Ocean in the west, and northward into the Arctic Ocean...

, and Panama
Panama
Panama , officially the Republic of Panama , is the southernmost country of Central America. Situated on the isthmus connecting North and South America, it is bordered by Costa Rica to the northwest, Colombia to the southeast, the Caribbean Sea to the north and the Pacific Ocean to the south. The...

, where a milder form of disease that spares the heart has been recognized. The two agents of HCPS in South America
South America
South America is a continent situated in the Western Hemisphere, mostly in the Southern Hemisphere, with a relatively small portion in the Northern Hemisphere. The continent is also considered a subcontinent of the Americas. It is bordered on the west by the Pacific Ocean and on the north and east...

 are Andes virus
Andes virus
Andes virus is a hantavirus, which, in South America, is a major causative agent of Hantavirus Cardiopulmonary Syndrome .-Background:...

 (also called Oran, Castelo de Sonhos, Lechiguanas, Juquitiba, Araraquara, and Bermejo viruses, among many other synonyms), which is the only hantavirus that has shown (albeit uncommonly) an interpersonal form of transmission, and Laguna Negra virus, an extremely close relative of the previously-known Rio Mamore virus. In the U.S., minor cases of HCPS include New York virus, Bayou virus, and possibly Black Creek Canal virus.

In the United States, as of July 2010 eight states had reported 30 or more cases of Hantavirus since 1993 - New Mexico
New Mexico
New Mexico is a state located in the southwest and western regions of the United States. New Mexico is also usually considered one of the Mountain States. With a population density of 16 per square mile, New Mexico is the sixth-most sparsely inhabited U.S...

 (84
Sin Nombre virus
The Sin Nombre virus is the prototypical etiologic agent of hantavirus cardiopulmonary syndrome ....

), Colorado
Colorado
Colorado is a U.S. state that encompasses much of the Rocky Mountains as well as the northeastern portion of the Colorado Plateau and the western edge of the Great Plains...

 (70), Arizona
Arizona
Arizona ; is a state located in the southwestern region of the United States. It is also part of the western United States and the mountain west. The capital and largest city is Phoenix...

 (62), California
California
California is a state located on the West Coast of the United States. It is by far the most populous U.S. state, and the third-largest by land area...

 (42), Washington (41), Texas
Texas
Texas is the second largest U.S. state by both area and population, and the largest state by area in the contiguous United States.The name, based on the Caddo word "Tejas" meaning "friends" or "allies", was applied by the Spanish to the Caddo themselves and to the region of their settlement in...

 (37), Utah
Utah
Utah is a state in the Western United States. It was the 45th state to join the Union, on January 4, 1896. Approximately 80% of Utah's 2,763,885 people live along the Wasatch Front, centering on Salt Lake City. This leaves vast expanses of the state nearly uninhabited, making the population the...

 (31) and Montana
Montana
Montana is a state in the Western United States. The western third of Montana contains numerous mountain ranges. Smaller, "island ranges" are found in the central third of the state, for a total of 77 named ranges of the Rocky Mountains. This geographical fact is reflected in the state's name,...

 (30). Other states reporting a significant number of cases include Idaho
Idaho
Idaho is a state in the Rocky Mountain area of the United States. The state's largest city and capital is Boise. Residents are called "Idahoans". Idaho was admitted to the Union on July 3, 1890, as the 43rd state....

 (16), Kansas
Kansas
Kansas is a US state located in the Midwestern United States. It is named after the Kansas River which flows through it, which in turn was named after the Kansa Native American tribe, which inhabited the area. The tribe's name is often said to mean "people of the wind" or "people of the south...

 (15), South Dakota
South Dakota
South Dakota is a state located in the Midwestern region of the United States. It is named after the Lakota and Dakota Sioux American Indian tribes. Once a part of Dakota Territory, South Dakota became a state on November 2, 1889. The state has an area of and an estimated population of just over...

 (15), and North Dakota
North Dakota
North Dakota is a state located in the Midwestern region of the United States of America, along the Canadian border. The state is bordered by Canada to the north, Minnesota to the east, South Dakota to the south and Montana to the west. North Dakota is the 19th-largest state by area in the U.S....

 (12). With only 11 cases, Oregon
Oregon
Oregon is a state in the Pacific Northwest region of the United States. It is located on the Pacific coast, with Washington to the north, California to the south, Nevada on the southeast and Idaho to the east. The Columbia and Snake rivers delineate much of Oregon's northern and eastern...

 has a notably lower attack rate overall and relative to population, compared to other Western states.

Hemorrhagic fever with renal syndrome


Hantavirus has an incubation time of two to four weeks in humans before symptoms of infection occur. The symptoms of HFRS can be split into five phases:
  • Febrile phase: Symptoms include fever
    Fever
    Fever is a common medical sign characterized by an elevation of temperature above the normal range of due to an increase in the body temperature regulatory set-point. This increase in set-point triggers increased muscle tone and shivering.As a person's temperature increases, there is, in...

    , chills, sweaty palms, diarrhea, malaise
    Malaise
    Malaise is a feeling of general discomfort or uneasiness, of being "out of sorts", often the first indication of an infection or other disease. Malaise is often defined in medicinal research as a "general feeling of being unwell"...

    , headache
    Headache
    A headache or cephalalgia is pain anywhere in the region of the head or neck. It can be a symptom of a number of different conditions of the head and neck. The brain tissue itself is not sensitive to pain because it lacks pain receptors. Rather, the pain is caused by disturbance of the...

    s, nausea
    Nausea
    Nausea , is a sensation of unease and discomfort in the upper stomach with an involuntary urge to vomit. It often, but not always, precedes vomiting...

    , abdominal
    Abdominal pain
    Abdominal pain can be one of the symptoms associated with transient disorders or serious disease. Making a definitive diagnosis of the cause of abdominal pain can be difficult, because many diseases can result in this symptom. Abdominal pain is a common problem...

     and back pain
    Back pain
    Back pain is pain felt in the back that usually originates from the muscles, nerves, bones, joints or other structures in the spine.The pain can often be divided into neck pain, upper back pain, lower back pain or tailbone pain...

    , respiratory problems such as the ones common in the influenza
    Influenza
    Influenza, commonly referred to as the flu, is an infectious disease caused by RNA viruses of the family Orthomyxoviridae , that affects birds and mammals...

     virus
    Virus
    A virus is a small infectious agent that can replicate only inside the living cells of organisms. Viruses infect all types of organisms, from animals and plants to bacteria and archaea...

    , as well as gastro-intestinal problems. These symptoms normally occur for three to seven days and arise about two to three weeks after exposure.
  • Hypotensive phase: This occurs when the blood platelet levels drop and symptoms can lead to tachycardia
    Tachycardia
    Tachycardia comes from the Greek words tachys and kardia . Tachycardia typically refers to a heart rate that exceeds the normal range for a resting heart rate...

     and hypoxemia
    Hypoxemia
    Hypoxemia is generally defined as decreased partial pressure of oxygen in blood, sometimes specifically as less than or causing hemoglobin oxygen saturation of less than 90%.-Distinction from anemia and hypoxia:...

    . This phase can last for 2 days.
  • Oliguric phase: This phase lasts for three to seven days and is characterised by the onset of renal failure
    Renal failure
    Renal failure or kidney failure describes a medical condition in which the kidneys fail to adequately filter toxins and waste products from the blood...

     and proteinuria
    Proteinuria
    Proteinuria means the presence of anexcess of serum proteins in the urine. The protein in the urine often causes the urine to become foamy, although foamy urine may also be caused by bilirubin in the urine , retrograde ejaculation, pneumaturia due to a fistula, or drugs such as pyridium.- Causes...

     occurs.
  • Diuretic phase: This is characterized by diuresis
    Polyuria
    Polyuria is a condition usually defined as excessive or abnormally large production or passage of urine . Frequent urination is sometimes included by definition, but is nonetheless usually an accompanying symptom...

     of three to six litres per day, which can last for a couple of days up to weeks.
  • Convalescent phase: This is normally when recovery occurs and symptoms begin to improve.


Formerly known as Korean hemorrhagic fever, HFRS is the term accepted by the World Health Organization
World Health Organization
The World Health Organization is a specialized agency of the United Nations that acts as a coordinating authority on international public health. Established on 7 April 1948, with headquarters in Geneva, Switzerland, the agency inherited the mandate and resources of its predecessor, the Health...

.

Hantavirus (cardio-)pulmonary syndrome


Hantavirus pulmonary syndrome (HPS) is an often fatal disease caused by hantavirus infection. The symptoms are very similar to those of HFRS and include tachycardia
Tachycardia
Tachycardia comes from the Greek words tachys and kardia . Tachycardia typically refers to a heart rate that exceeds the normal range for a resting heart rate...

 and tachypnea
Tachypnea
Tachypnea means rapid breathing. Any rate between 12-20 breaths per minute is normal. Tachypnea is a respiration rate greater than 20 breaths per minute. - Distinction from other breathing terms :...

. Additionally, patients will develop difficulty breathing, coughing and shortness of breath. Such conditions can lead to a cardiopulmonary phase, where cardiovascular shock can occur, and hospitalization of the patient is required. HPS was first recognized in 1993 in the southwest of the United States by Bruce Tempest MD, and was originally called "Four Corners disease". It has since been identified throughout the United States. Although rare, HPS is fatal in up to 60% of cases. Rodent control in and around the home remains the primary strategy for preventing hantavirus infection. People suspecting illness are encouraged to contact their local health department.

Weaponization


Korean hemorrhagic fever (Hantavirus) was one of three hemorrhagic fevers and one of more than a dozen agents that the United States researched as potential biological weapons before suspending its biological weapons program
United States and weapons of mass destruction
The United States is known to have possessed three types of weapons of mass destruction: nuclear weapons, chemical weapons and biological weapons. The U.S. is the only country to have used nuclear weapons in combat. The U.S. also used chemical weapons in World War I...

.

Prevention and treatment


There is no known antiviral treatment, but natural recovery from the virus is possible. Patients with suspected hantavirus are usually admitted to hospital and given oxygen to help them breathe. As the virus can be transmitted by rodent saliva, excretia 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 get in, laying down poisons or using natural predators such as cats in the home.

Evolution


Findings of significant congruence between phylogenies of hantaviruses and phylogenies of their rodent reservoirs have led to the theory – well accepted until recently – of long-standing hantavirus–rodent host coevolution. However, recent findings have led to scientific debate and new hypotheses regarding hantavirus evolution.

Various hantaviruses have been found to infect multiple rodent species, and cases of cross-species transmission (host switching) 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, hantaviruses have been found in multiple species of shrews and moles.

Taking into account the inconsistencies in the theory of coevolution, Ramsden et al. (2009) have proposed 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. Ulrich et al. (2010) have proposed that the observed 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 Rodentia and Soricomorpha, Yanagihara et al. (2011) have proposed that the evolutionary history of the hantavirus consists of a complex mix of both host switching and codivergence and suggest that ancestral shrews or moles rather than rodents may have been the early original hosts of ancient hantaviruses.

See also

  • Sweating sickness
    Sweating sickness
    Sweating sickness, also known as "English sweating sickness" or "English sweate" , was a mysterious and highly virulent disease that struck England, and later continental Europe, in a series of epidemics beginning in 1485. The last outbreak occurred in 1551, after which the disease apparently...

    , which may have been caused by a hantavirus
  • List of cutaneous conditions

External links