Orthohantavirus is a genus of viruses that includes all hantaviruses (family Hantaviridae) that cause disease in humans. Orthohantaviruses, hereafter referred to as hantaviruses, are naturally found primarily in rodents. In general, each hantavirus is carried by one rodent species and each rodent that carries a hantavirus carries one hantavirus species. Hantaviruses in their natural reservoirs usually cause an asymptomatic, persistent infection. In humans, however, hantaviruses cause two diseases: hemorrhagic fever with renal syndrome (HFRS) and hantavirus pulmonary syndrome (HPS). HFRS is mainly caused by hantaviruses in Africa, Asia, and Europe, called Old World hantaviruses, and HPS is usually caused by hantaviruses in the Americas, called New World hantaviruses.

Hantaviruses are transmitted mainly through aerosols and droplets that contain rodent excretions, as well as through contaminated food, bites, and scratches. Environmental factors such as rainfall, temperature, and humidity influence transmission. Human-to-human transmission does not occur. HFRS is marked by kidney disease with kidney swelling, excess protein in urine, and blood in urine. The case fatality rate of HFRS varies from less than 1% to 15% depending on the virus. A mild form of HFRS often called nephropathia epidemica is often caused by Puumala virus and Dobrava-Belgrade virus. For HPS, initial symptoms are flu-like, with fever, headache, and muscle pain, followed by sudden respiratory failure. HPS has a much higher case fatality rate than HFRS, at 30–60%. For both HFRS and HPS, illness is the result of increased vascular permeability, decreased platelet count, and overreaction of the immune system.

Individual hantavirus particles (virions) are usually spherical and vary at 70–350 nanometers in diameter. They consist of the viral RNA, which is segmented into three parts and encased in helical nucleocapsids to form three ribonucleoprotein (RNP) complexes. Attached to each RNP is a viral RNA-dependent RNA polymerase (RdRp). RNPs are surrounded by a lipid envelope that has spike proteins emanating from its surface. Each part of the viral genome is single-stranded negative-sense RNA. The segments encode one protein each: RdRp, which performs transcription and replication of the genome, a glycoprotein precursor, which is formed into surface spikes on the envelope, and the N protein, which binds to and protects viral RNA. Some hantaviruses encode on the same segment as the N protein a non-structural protein that inhibits host interferon production.

Hantavirus replication begins by attaching to the surface of cells, usually vascular endothelial cells and macrophages. They then enter the cell and form vesicles to be transferred to endosomes and lysosomes. The viral envelope fuses with the membranes of endosomes and lysosomes, which empties the viral RNPs into the host cell's cytoplasm. RdRp then transcribes the viral genome to produce messenger RNA (mRNA) for translation by host ribosomes to produce viral proteins. RdRp also produces copies of the viral genome for progeny viruses. Old World hantavirus virions are constructed in the Golgi apparatus and obtain their envelope from the Golgi apparatus, before being transported to the cell membrane to leave the cell via exocytosis. New World hantavirus virions are constructed near the cell membrane, obtain their envelope from the cell membrane, and leave the cell by budding from its surface.

Hantaviruses were first discovered following the Korean War. During the war, HFRS was a common ailment in soldiers stationed near the Hantan river. In 1978 in South Korea, the first hantavirus was isolated, Hantaan virus, and was shown to be responsible for the outbreak during the war. Within a few years, other hantaviruses that cause HFRS were discovered throughout Eurasia. In 1982, the World Health Organization gave HFRS its name, and in 1987, hantaviruses were classified for the first time, and they collectively bear the name of Hantaan virus and the Hantan river. In 1993, an outbreak of HPS occurred in the Four Corners region in the United States, which led to the discovery of pathogenic New World hantaviruses and the second disease caused by hantaviruses. Since then, hantaviruses have been found not just in rodents but also shrews and bats.