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Hantaan virus ( HTNV) is the main cause of hemorrhagic fever with renal syndrome (HFRS) in East Asia. Hantaan virus is transmitted by the striped field mouse ( Apodemus agrarius). In its natural reservoir, HTNV causes a persistent, asymptomatic infection and is spread through excretions, fighting, and grooming. Humans can become infected by inhaling aerosols that contain rodent saliva, urine, or feces, as well as through bites and scratches. In humans, infection causes symptoms such as fever and headache, as well as the appearance of spots on the skin, hepatitis, and renal symptoms such as kidney swelling, excess protein in urine, blood in urine, decreased urine production, and kidney failure. Rarely, HTNV infection affects the pituitary gland and can cause empty sella syndrome. The case fatality rate from infection is up to 6.3%.
The genome of HTNV is about 11.9 kilobases (kb) in length and segmented into three negative-sense, single-stranded RNA (-ssRNA) strands. The small strand encodes the viral nucleoprotein, the medium strand encodes the viral spike protein, which attaches to cell receptors for entry into cells, and the long strand encodes the viral RNA-dependent RNA polymerase (RdRp), which replicates and transcribes the genome. Genome segments are encased in nucleoproteins to form ribonucleoprotein (RNP) complexes that are surrounded by a viral envelope that contains spikes emanating from its surface.
Hantaan virus replicates first by binding to the surface of cells with its envelope spikes. Virus particles, called virions, are then taken into the cell by , where a drop in pH causes the viral envelope to fuse with the endosome, which releases viral RNA into the host cell. RdRp then transcribes the genome for translation by host cell ribosomes and produces copies of the genome for progeny viruses. New virions are assembled at the endoplasmic reticulum and bud from its surface to obtain their viral envelope. Progeny viruses are then transported by a cellular vesicle to the cell membrane, where they leave the cell by exocytosis.
HTNV was discovered in 1976 then isolated in 1978 after being extracted from striped field mice. The virus was subsequently linked to a past outbreak among soldiers in the Korean War who were stationed near the Hantan river and for that was named after the river. Hantaan virus was the first hantavirus to be discovered, and the group is named after the virus. The vast majority of HFRS cases occur in China, where Hantaan virus is responsible for up to 70% of cases. Cases of HFRS caused by Hantaan virus also occur in South Korea, Russia, and Vietnam.
For replication of the genome, a complementary positive-sense strand is produced by RdRp. Copies of the genome are made from this complementary strand. Progeny RNA strands are then encapsidated by nucleoproteins. During replication, the glycoprotein is cleaved in the endoplasmic reticulum by the host signal peptidase during translation. This produces Gn at the N-terminus and Gc at the C-terminus of the protein. Spike proteins are expressed on the surface of the endoplasmic reticulum. Viral RNPs are transported to the endoplasmic reticulum where they bud from the surface, thereby obtaining their envelope. Progeny viruses are then transported by a cellular vesicle to the cell membrane, where they leave the cell via exocytosis.
In its rodent hosts, HTNV causes a persistent and mainly asymptomatic infection. Rodent-to-rodent transmission occurs through contact with bodily fluids and through fighting and grooming. Transmission to humans occurs mainly through the inhalation of aerosols that contain rat saliva, urine, or feces. Transmission can also occur through consumption of contaminated food, bites, and scratches. Infections with Hantaan virus mainly occur in rural settings such as in residences near crop fields or in such fields. In China, cases most commonly occur during the autumn harvest season when farmers work on and sometimes sleep in crop fields.
Infection with Hantaan virus mainly occurs in China and South Korea, but also in Russia and Vietnam. The vast majority of HFRS cases in the world are in China, and Hantaan virus is responsible for up to 70% of cases. 9,000–12,000 cases occur each year in China, and about 400–600 per year in South Korea. HTNV infection is diagnosed based on observation of symptoms and testing for hantavirus nucleic acid, proteins, or hantavirus-specific antibodies. Treatment is supportive in nature and includes intravenous hydration, electrolyte therapy, platelet transfusions, and, in cases of kidney injury or failure, intermittent dialysis and continuous renal replacement therapy. Avoiding or minimizing contact with rodents is key to prevent infection. In China and South Korea, bivalent vaccines for Seoul virus and Hantaan virus are available for use. Repeated infections of hantaviruses have not been observed, so recovering from infection likely grants life-long immunity.
In 1976, Ho Wang Lee (Korean: 이호왕) showed that taken from the lungs of striped field mice were reactive to antibodies from sera of people who had Korean hemorrhagic fever. The virus couldn't be isolated in 1976 but testing showed that an infectious agent was responsible. The virus was isolated for the first time in 1978 and named "KHF strain 76-118". It was propagated in cell cultures for the first time in 1981 and renamed "Hantaan virus, strain 76-118" after the Hantan river. Around the same time, other viruses related to Hantaan virus that caused HFRS were discovered throughout Asia and Europe. This group of newly discovered were given the name "hantaviruses", taking the name of Hantaan virus.
Hantaan virus was accepted as a species by the International Committee on Taxonomy of Viruses in 1987, and with it the establishment a genus for hantaviruses. It has undergone a series of changes to its species name, first changing to Hantaan hantanavirus, then Hantaan orthohantavirus, and most recently to the current Orthohantavirus hantanense. In 1989, the method to diagnose Hantaan virus infection was developed by Lee and just a year later he developed a vaccine against it, which made him the first person in history to discover the cause of a viral disease, develop a method to diagnose it, and develop a vaccine against it.
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