Hantavirus

Overview
Hantaviruses belong to the bunyaviridae family of viruses. There are 5 genera within the bunyaviridae family: bunyavirus, phlebovirus, nairovirus, tospovirus, and hantavirus. Each is made up of negative-sensed, single-stranded RNA viruses. All these genera include arthropod-borne viruses, with the exception of hantavirus, which is a genus of rodent-borne agents.

The word hantavirus is derived from the Hantan River, where the Hantaan virus (the etiologic agent of Korean hemorrhagic fever) was first isolated by Dr. Lee Ho-Wang. 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 class of virus; 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 viruses). 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 (only in a few clusters of cases) 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 causes of HCPS include New York virus, Bayou virus, and possibly Black Creek Canal virus.

As of July of 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 (30). 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 RNA segments designated S (small), M (medium), and L (large). All hantaviral genes are encoded in the negative (genome complementary) sense. 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 each genomic segment.

Hantaviruses replicate exclusively in the host cell cytoplasm. 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.

Hemorrhagic Fever with Renal Syndrome (HFRS)
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 3-7days.


 * 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 (HPS or HCPS)
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 tachypnoea. Such conditions can lead to a cardiopulmonary phase, where cardiovascular shock can occur, and hospitalization of the patient is required.