Ортохантавирустар: Қауіпті инфекциялар және аурулары

Genus of viruses

Orthohantavirus is a genus of single stranded, enveloped, negative sense RNA viruses in the family Hantaviridae within the order Bunyavirales. Members of this genus may be called orthohantaviruses or simply hantaviruses. Orthohantaviruses typically cause chronic asymptomatic infection in rodents. Humans may become infected with hantaviruses through contact with rodent urine, saliva, or feces. Some strains cause potentially fatal diseases in humans, such as hantavirus hemorrhagic fever with renal syndrome (HFRS), or hantavirus pulmonary syndrome (HPS), also known as hantavirus cardiopulmonary syndrome (HCPS), while others have not been associated with known human disease (e. g. Prospect Hill virus). HPS (HCPS) is a "rare respiratory illness associated with the inhalation of aerosolized rodent excreta (urine and feces) contaminated by hantavirus particles". Orthohantaviruses are named for the Greek word ortho meaning "straight" or "true" and for the Hantan River in South Korea, where the first member species (Hantaan virus) was identified and isolated in 1976 by Ho Wang Lee.

Hantavirus infections in humans are associated with two diseases: hemorrhagic fever with renal syndrome (HFRS) and hantavirus pulmonary syndrome (HPS), caused by Old World and New World hantaviruses, respectively. A common feature of the two diseases is increased vascular permeability, which causes hypotension, thrombocytopenia, and leukocytosis. The pulmonary illness is the more fatal of the two, whereas the hemorrhagic fever is much more common. Treatment for both is primarily supportive as there is no specific treatment for hantavirus infections. While many hantaviruses cause either of the two diseases, some are not known to cause illness, such as the Prospect Hill orthohantavirus.

Hemorrhagic fever with renal syndrome (HFRS) is caused chiefly by hantaviruses in Asia and Europe. Clinical presentation varies from subclinical to fatal, depending on the virus. After an incubation period of 2–4 weeks, the typical illness starts with non specific symptoms such as high fever, chills, headache, backache, abdominal pains, nausea, and vomiting. After the initial period, bleeding under the skin begins, often paired with low blood pressure, followed by further internal bleeding throughout the body. Renal dysfunction leading to further health issues begins thereafter, which may cause death. Trench nephritis during World War I is now thought to have been HFRS.

Hantavirus pulmonary syndrome (HPS), also called hantavirus cardiopulmonary syndrome (HCPS), is usually caused by hantaviruses in the Americas. Its incubation period ranges from 16 to 24 days. Illness initially shows similar symptoms as HFRS. After a few days of non specific symptoms, sudden onset of progressive, or productive, coughing, shortness of breath, and elevated heart rate occur due to fluid buildup in the lungs. These symptoms are accompanied by impairment of lymphoid organs. Death from cardiovascular shock may occur rapidly after the appearance of severe symptoms. 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. As with other Bunyavirales, each of the three segments has a consensus 3′ terminal nucleotide sequence (AUCAUCAUC), which is complementary to the 5′ terminal sequence and is distinct from those of the other four genera in the family. These sequences appear to form panhandle structure which seem likely to play a role in replication and encapsidation facilitated by binding with the viral nucleocapsid (N) protein. The large segment is 6530–6550 nucleotides (nt) in length, the medium is 3613–3707 nt in length and the small is 1696–2083 nt in length. No nonstructural proteins are known, unlike the other genera in this family. At the 5′ and 3′ of each segment are short noncoding sequences: the noncoding segment in all sequences at the 5′ end is 37–51 nt. The 3′ noncoding regions differ: L segment 38–43 nt; M segment 168–229 nt; and S segment 370–730 nt. The 3′ end of the S segment is conserved between the genera suggesting a functional role.

Viral entry into host cells initiates by binding to surface cell receptors. Integrins are considered to be the main receptors for hantaviruses in vitro, but complement decay accelerating factor (DAF) and globular heads of complement C1q receptor (gC1qR) have mediated attachment in cultured cells too. Entry may proceed through a number of possible routes, including clathrin dependent endocytosis, clathrin independent receptor mediated endocytosis, and micropinocytosis. Viral particles are then transported to late endosomes. Gc mediated membrane fusion with the endosomal membrane, triggered by low pH, releases the nucleocapsid into the cytoplasm. The G1 (or 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.

The pathogenesis of hantavirus infections is unclear as there is a lack of animal models to describe it (rats and mice do not seem to acquire severe disease). While the primary site of viral replication in the body is not known, in HFRS the main effect is in the blood vessels while in HPS most symptoms are associated with the lungs. In HFRS, there are increased vascular permeability and decreased blood pressure due to endothelial dysfunction and the most dramatic damage is seen in the kidneys, whereas in HPS, the lungs, spleen, and gall bladder are most affected. Early symptoms of HPS tend to present similarly to the flu (muscle aches, fever and fatigue) and usually appear around 2 to 3 weeks after exposure. Later stages of the disease (about 4 to 10 days after symptoms start) include difficulty breathing, shortness of breath and coughing.

Findings of significant congruence between phylogenies of hantaviruses and phylogenies of their rodent reservoirs have led to the theory that rodents, although infected by the virus, are not harmed by it because of long standing hantavirus–rodent host coevolution, although findings in 2008 led to new hypotheses regarding hantavirus evolution. Various hantaviruses have been found to infect multiple rodent species, and cases of cross species transmission (host switching) have been recorded. Additionally, rates of substitution based on nucleotide sequence data reveal that hantavirus clades and rodent subfamilies may not have diverged at the same time. Furthermore, as of 2007 hantaviruses have been found in multiple species of non rodent shrews and moles. Taking into account the inconsistencies in the theory of coevolution, it was proposed in 2009 that the patterns seen in hantaviruses in relation to their reservoirs could be attributed to preferential host switching directed by geographical proximity and adaptation to specific host types. The evolution of shrew borne hantaviruses appears to have involved natural occurrences of homologous recombination events and the reassortment of genome segments. The evolution of Tula orthohantavirus carried by the European common vole also appears to have involved homologous recombination events.

According to the U. S. CDC, the best prevention against contracting hantavirus is to eliminate or minimize contact with rodents in the home, workplace, or campsite. As the virus can be transmitted by rodent saliva, excretions, and bites, control of rats and mice in areas frequented by humans is key for disease prevention. General prevention can be accomplished by disposing of rodent nests, sealing any cracks and holes in homes where mice or rats could enter, setting traps, or laying down poisons or using natural predators such as cats in the home.

, no vaccines against hantaviruses have been approved by the U. S. FDA, but whole virus inactivated bivalent vaccines against Hantaan virus and Seoul virus are available in China and South Korea. In both countries, the use of the vaccine, combined with other preventive measures, has significantly reduced the incidence of hantavirus infections. Apart from these vaccines, four types of vaccines have been researched: DNA vaccines targeting the M genome segment and the S genome segment, subunit vaccines that use recombinant Gn, Gc, and N proteins of the virus, virus vector vaccines that have recombinant hantavirus proteins inserted in them, and virus like particle vaccines that contain viral proteins, but lack genetic material. Of these, only DNA vaccines have entered into clinical trials.

Ribavirin may be a drug for HPS and HFRS, but its effectiveness remains unknown; still, spontaneous recovery is possible with supportive treatment. People with suspected hantavirus infection may be admitted to a hospital, and given oxygen and mechanical ventilation support to help them breathe during the acute pulmonary stage with severe respiratory distress. Immunotherapy, administration of human neutralizing antibodies during acute phases of hantavirus, has been studied only in mice, hamsters, and rats. No controlled clinical trials have been reported.

Hantavirus infections have been reported from all continents except Australia. 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 hantavirus pulmonary syndrome include Argentina, Chile, Brazil, the United States, Canada, and Panama.

In 2010, a novel hantavirus, Sangassou virus, was isolated in Africa, which causes HFRS.

In China, Hong Kong, the Korean Peninsula, and Russia, HFRS is caused by Hantaan, Puumala, and Seoul viruses.

In March 2020, a man from Yunnan tested positive for hantavirus. He died while travelling to Shandong for work on a chartered bus. According to the Global Times reports, around 32 other people have been tested for the virus.

, no human infections have been reported in Australia, though rodents were found to carry antibodies.

In Europe, two hantaviruses – Puumala and Dobrava Belgrade viruses – are known to cause HFRS. Puumala usually causes a generally mild disease, nephropathia epidemica, which typically presents with fever, headache, gastrointestinal symptoms, impaired renal function, and blurred vision. Dobrava infections are similar, except that they often also have hemorrhagic complications. Puumala virus is carried by its rodent host, the bank vole (Clethrionomys glareolus), and is present throughout most of Europe, except for the Mediterranean region. Four Dobrava virus genotypes are known, each carried by a different rodent species. Genotype Dobrava is found in the yellow necked mouse (Apodemus flavicollis), genotypes Saaremaa and Kurkino in the striped field mouse (Apodemus agrarius), and genotype Sochi in the Black Sea field mouse (Apodemus ponticus). In 2017 alone, the Robert Koch Institute (RKI) in Germany received 1,713 notifications of hantavirus infections.

The primary cause of the disease in Canada is Sin Nombre virus infected deer mice. Between 1989 and 2014, 109 confirmed cases were reported, with the death rate estimated at 29%.

In Mexico, rodents have been found to carry hantaviruses include Thomas's giant deer mouse (Megadontomys thomasi), the pack rat Neotoma picta, Orizaba deer mouse (Peromyscus beatae), Western harvest mouse (Reithrodontomys megalotis) and Sumichrast's harvest mouse (Reithrodontomys sumichrasti).

Agents of HPS found in South America include the Andes virus (also called Oran, Castelo de Sonhos – Portuguese for "Castle of Dreams", Lechiguanas, Juquitiba, Araraquara, and Bermejo virus, among many other synonyms), which is the only hantavirus that has shown an interpersonal form of transmission, and the Laguna Negra virus, an extremely close relative of the previously known Rio Mamore virus. Rodents that have been shown to carry hantaviruses include Abrothrix longipilis and Oligoryzomys longicaudatus.

Hantavirus HFRS was likely first referenced in China in the 12th century. The first clinical recognition was in 1931 in northeast China. Around the same time in the 1930s, NE was identified in Sweden. HFRS came to the recognition of western physicians during the Korean War between 1951 and 1954 when more than 3,000 United Nations soldiers fell ill in an outbreak. In 1976, the first pathogenic hantavirus, the Hantaan orthohantavirus, was isolated from rodents near the Hantan River in South Korea. Other prominent hantaviruses that cause HFRS, including the Dobrava Belgrade orthohantavirus, Puumala orthohantavirus, and Seoul orthohantavirus, were identified in the years after then and are collectively referred to as the Old World hantaviruses. The hypothesis was criticized because sweating sickness was recorded as being transmitted from human to human, whereas hantaviruses were not known to spread in this way.