Hantavirus

Submitted To: Dr. Mazhar Qayyum Submitted By: Farhat Yasmeen 07-arid-1172 4th Semester

M.Sc Zoology (Eve.)

Hantavirus Hantaviruses belong to the Bunyaviridae family of viruses. The 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 Hantan 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 hemorrhagic fever with renal syndrome (HFRS), a term that is accepted by the World Health Organization. It was formerly called Korean hemorrhagic fever (a term that is no longer in use).

Transmission electron micrograph of the Sin Nombre Hantavirus

Virus classification Group: Group V ((-)ssRNA) Family: Bunyaviridae Genus: Hantavirus Specie: Hantaan virus

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.

Virology 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 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. 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 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.

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 HFRS, the most dramatic damage is seen in the kidneys, whereas in HPS, the lungs and spleen are most affected.

Epidemiology Prevalence

The cotton rat Sigmodon hispidus is a hantavirus carrier that becomes a threat when it enters human habitation in rural and suburban areas.

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.

Diagnosis of Hantavirus Infection Diagnosis is made and clinically supported by immunological lab tests.

Treatment of Hantavirus Infection People who live in areas where hantavirus illnesses have occurred should take precautions to rodent-proof their homes and make outdoor areas as inhospitable to rodents as possible. People who live in areas not yet touched by hantavirus should avoid contact with rodents and be cautious about cleaning up their nests or droppings. Public health officials emphasize that most tourist activities pose little or no risk, and that travelers need not worry about visiting areas where hantavirus has cropped up. Campers, however, should seek advice locally about avoiding native rodents. Ribavirin, an antiviral drug, may be of some benefit. But what appears to help most is being hospitalized early, monitored carefully, and treated with life-sustaining fluids and medications that help normalize heart rate and breathing.

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.

Hantavirus Infections: Words to Know Hemodialysis: A mechanical method for cleansing blood outside the body.

Hemorrhagic: Relating to a condition in which there is massive, difficult-to-control bleeding.

Platelets: Blood cells that have a role in the process of blood clotting.

Pulmonary: Relating to the lungs.

Renal: Relating to the kidneys.

Shock:

A condition in which blood pressure drops suddenly and the flow of blood to cells is dramatically reduced. Because of this reduced flow, cells are not able to get the oxygen they need.

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, sweaty palms, explosive diarrhea, 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.

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

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Diuretic phase: This is characterized by diuresis of 3–6L per day, which can last for a couple of days up to weeks.

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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

How can hantavirus pulmonary syndrome be prevented? • The best way to prevent HPS is to avoid contact with rodents and to avoid inhaling dust that might be contaminated with rodent saliva, urine, or droppings.

• Control mice inside. Keep the kitchen clean, and store food and trash in containers with tight lids. Carefully dispose of dead rodents trapped indoors or brought inside by pets. Rodent-proof the house by sealing cracks and clearing brush from around foundations. • Control mice outside. Eliminate possible nesting sites. Elevate hay, woodpiles, and garbage cans, and place them away from the house. Store animal food in closed containers. • Use safety precautions when cleaning indoor or outdoor areas that might be contaminated with rodent saliva, urine, or droppings. Do not stir up and breathe dust. Before cleaning, wet down potentially contaminated areas with a household disinfectant (such as bleach or alcohol). While cleaning, wear rubber gloves, and disinfect them after use. Dust masks that cover the nose and mouth can also help. • When participating in outside activities, stay clear of rodents and their burrows and nests. Keep campsites clean and food tightly sealed. Open up and air out outbuildings and rural or wilderness cabins before entering or cleaning. Remove garbage and trash before leaving.

Sweating sickness Sweating sickness, also known as the "English sweate" (Latin: sudor anglicus), was a mysterious and highly virulent disease which struck England and later Europe in a series of epidemics, the first beginning in 1485 and the last in 1551, afterwards apparently vanishing. The onset of symptoms was dramatic and sudden, with death often occurring within hours. Its cause remains unknown. One suspect is a hantavirus.

Prevention of Hantavirus Infection Since infection is thought to occur by inhalation of rodent wastes (excreta), prevention is aimed toward eradication of rodents in houses and avoidance of exposure to rodent excreta in rural settings.