hantavirus

[hahn-tuh-vahy-ruhs, han‐]

hantavirus, any of a genus (Hantavirus) of single-stranded RNA viruses that are carried by rodents and transmitted to humans when they inhale vapors from contaminated rodent urine, saliva, or feces. There are many strains of hantavirus. The first to be isolated (1976) was the Hantaan virus (from the Han River in South Korea, which also gives the species its name). Hantaan virus and its related strains, Seoul virus and Puulmala virus, cause Korean hemorrhagic fever (more correctly, hemorrhagic fever with renal syndrome), a condition in which the capillaries of the circulatory system begin to leak blood. Although some people with the disease are nearly asymptomatic, in others it can lead to shock, acute kidney failure, and, in 10% of cases, death.

A second disease, hantavirus pulmonary syndrome, was identified in the United States in 1993 and is caused by at least three strains of the virus. It is known to be carried by deer mice, white-footed mice, and cotton rats. This disease is much more deadly, causing flulike symptoms that can lead to fluid accumulation in the lungs and death. One of the pulmonary strains, the Sin Nombre virus (named for a Spanish massacre of Native Americans that occurred in the canyon where it was discovered), was the cause of a 1993 outbreak in the Four Corners area of the SW United States that killed 32 of 53 people known to have been infected. Sporadic occurrences of hantavirus pulmonary syndrome still occur in North America. Outbreaks of a hantavirus strain that apparently can be spread from person to person occurred in South America in 1996 and 1997. There is no vaccination for pulmonary hantavirus. Treatment includes respiratory and hemodynamic support; the antiviral drug ribavirin has been effective in some cases.

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hantavirus

Genus of viruses of the family Bunyaviridae that cause pneumonia and hemorrhagic fevers. Carried by rodents, they spread to humans directly or by inhalation but apparently are not transmitted from one person to another. An outbreak in the 1990s in the southwestern U.S. caused a mysterious, often fatal, flulike illness with rapid respiratory failure in previously healthy adults. The culprit was a hantavirus type carried by mice and not previously associated with human illness in the U.S.

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Encyclopedia Britannica, 2008. Encyclopedia Britannica Online.

Hantavirus

Hantaviruses belong to the Bunyaviridae family of viruses. There Bunyaviridae family is divided into 5 genera: Orthobunyavirus, Nairovirus, Phlebovirus, Tospovirus, and Hantavirus. Like all members of this family, hantaviruses have genomes comprised of three negative-sense, single-stranded RNA segments, and so are classified as negative sense RNA viruses. Viruses in the genus Hantavirus are unique in that they are transmitted by aerosolized rodent excreta or rodent bites, whereas all other genera in the Bunyaviridae family are arthropod-borne viruses.

The name hantavirus is derived from the Hantaan River, where the Hantaan virus (the etiologic agent of Korean hemorrhagic fever) was first isolated by Dr. Ho-Wang Lee and colleagues. The disease associated with Hantaan virus is called Korean hemorrhagic fever (a term that is no longer in use) or hemorrhagic fever with renal syndrome (HFRS), a term that is accepted by the World Health Organization.

History

The hantaviruses constitute a relatively newly discovered genus of viruses; the disease entity HFRS was first recognized by Western medicine during the Korean War in the early 1950s. In 1993, a newly-recognized species of hantavirus was found to be behind the Hantavirus cardiopulmonary syndrome (HCPS, also called HPS) caused by the Sin Nombre virus (Spanish for "nameless virus") in New Mexico and other Four Corners states. In addition to Hantaan virus and Sin Nombre virus, several other hantaviruses have been implicated as etiologic agents for either HFRS or HCPS.

Geographic distribution and epidemiology

Regions especially affected by HFRS include China, the Korean Peninsula, Russia (Hantaan, Puumala and Seoul viruses), and northern and western Europe (Puumala and Dobrava virus). Regions with the highest incidences of HCPS include Patagonian Argentina, Chile, Brazil, the United States, Canada, and Panama, where a milder form of disease that spares the heart has been recognized. The two agents of HCPS in South America are Andes virus (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.

As of July 2007, six states had reported 30 or more cases of Hantavirus since 1993 - New Mexico (69), Colorado (49), Arizona (46), California (43), Texas (33), and Washington (31). Other states reporting a significant number of cases include Montana (25), Idaho (19), and Utah (24). With only 7 cases, Oregon has a notably lower attack rate overall and relative to population, compared to other Western states.

Virology

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 glycoproteins G1 and 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.

Entry into host cells is thought to occur by attachment of virions to cellular receptors and subsequent endocytosis. Nucleocapsids are introduced into the cytoplasm by pH-dependent fusion of the virion with the endosomal membrane. 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 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 and released by exocytosis.

Symptoms

Renal syndrome

Hantavirus has an incubation time of 2-4 weeks in humans, before symptoms of infection occur. These symptoms can be split into five phases:

Febrile phase: Symptoms include fever, chills, malaise, headaches, nausea, abdominal and back pain, respiratory problems such as the ones common in the influenza virus, as well as gastro-intestinal problems. These symptoms normally occur for 3-7 days.

Hypotensive phase: This occurs when the blood platelet levels drop and symptoms can lead to tachycardia and hypoxemia. This phase can last for 2 days.

Oliguric phase: This phase lasts for 3-7 days and is characterised by the onset of renal failure and proteinuria occurs.

Diuretic phase: This is characterized by diuresis of 3-6L 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.

Hantavirus (cardio-)pulmonary syndrome

Hantavirus pulmonary syndrome (HPS) is a deadly disease transmitted by infected rodents through urine, droppings, or saliva. Humans can contract the disease when they breathe in aerosolized virus. HPS was first recognized in 1993 and has since been identified throughout the United States. Although rare, HPS is potentially deadly. Rodent control in and around the home remains the primary strategy for preventing hantavirus infection.

These symptoms, which are very similar to HFRS, include tachycardia and tachypnea. Such conditions can lead to a cardiopulmonary phase, where cardiovascular shock can occur, and hospitalization of the patient is required.

Pathogenesis

The pathogenesis of Hantavirus infections is unclear as there is a lack of animal models (rats and mice do not seem to acquire severe disease). While the primary replication site is not clear, in both HFRS and HPS, the main effect is in the blood vessels. There is increased vascular permeability and decreased blood pressure due to endothelial dysfunction. In HFPS, the most dramatic damage is seen in the kidneys, whereas in HPS, the lungs and spleen are most affected.