Sin Nombre virus

Genome

The genome of Sin Nombre virus is about 12.3 thousand nucleotides in length and segmented into three negative-sense, single-stranded RNA (-ssRNA) strands. The segments form into circles via non-covalent bonding of the ends of the genome. The small segment, about 2.06 kilobases (kb) in length, encodes the viral nucleoprotein and a non-structural protein that inhibits interferon production. The medium segment, about 3.7* kb in length, encodes a glycoprotein precursor that is cleaved into the two spike proteins Gn and Gc during virion assembly. The large segment, about 6.56 *kb in length, encodes the viral RNA-dependent RNA polymerase (RdRp), which is responsible for transcribing and replicating the genome. The ends of each segment contain untranslated terminal regions (UTRs) that are involved in the replication and transcription of the genome.

Structure

Virions are mostly spherical or pleomorphic in shape, with an average diameter of 112 nanometers (nm). They contain a lipid envelope covered in spike proteins made of the two viral glycoproteins, Gn and Gc. The spike proteins extend about 10* nm out from the surface and are tetrameric, consisting of four copies each of Gn and Gc with helical symmetry, in which Gn forms the stalk of the spike and Gc the head. Spikes are arranged on the surface in a lattice pattern. Inside the envelope are the three genome segments, which are encased in nucleoproteins to form a ribonucleoprotein (RNP) complex. Attached to each RNP complex is a copy of RdRp. For some SNV strains, virions may be roughly tubular in shape, with an average diameter of 85 nm and an average length of 180 *nm.

Life cycle

SNV primarily infects endothelial cells and macrophages.

For replication of the genome, a complementary positive-sense strand is produced by RdRp. Copies of the genome are made from this complementery strand. Progeny RNA strands are then encapsidated by nucleoproteins.

Evolution

The most common way that hantaviruses evolve is through mutations of individual nucleotides being inserted, deleted, or substituted. Because Sin Nombre virus has a segmented genome, it is possible for recombination and reassortment of segments to occur, whereby segments from different lineages mix in a single host cell and produce hybrid progeny. This has been observed for SNV in the US, mainly in exchanges of the S and M segments.

Ecology

Sin Nombre virus is carried chiefly by the western deer mouse (Peromyscus sonoriensis). Many other rodents, such as desert woodrats (Neotoma lepida), are considered to be dead-end hosts for SNV. The distribution of SNV closely matches that of its host's distribution. The western deer mouse is found in most of the United States west of the Mississippi River, as well as in most of southwestern Canada. P. sonoriensis mainly lives in rural areas, which mirrors where HPS cases typically occur.

In its rodent hosts, SNV causes a persistent, asymptomatic infection. The main sites of replication in deer mice are the heart, lungs, and brown adipose tissue. 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 mouse saliva, urine, or feces. Transmission can also occur through consumption of contaminated food, bites, and scratches. Antibodies to Sin Nombre virus have been detected in cats and dogs, but the role of these animals as hosts is unknown.

Disease

Main article: Hantavirus pulmonary syndrome

Sin Nombre virus infection usually causes hantavirus pulmonary syndrome (HPS), also called hantavirus cardiopulmonary syndrome (HCPS). Symptoms occur within 1–8 weeks after exposure to the virus and come in three phases: prodromal, cardiopulmonary, and recovery. Prodromal, a.k.a. early, symptoms last for a few days and include fever, muscle pain, headache, coughing, nausea, vomiting, chills, and dizziness. The cardiopulmonary phase lasts for several days and is characterized by fluid buildup in the lungs, low oxygen levels in the blood, elevated or irregular heart rate, low blood pressure, cardiogenic shock, and respiratory failure. The case fatality rate from SNV infection is 30–50%.

SNV is the most common cause of HPS in the North America, In the US and Canada, most cases occur in the west.

Classification

Sin Nombre virus is classified into the species Orthohantavirus sinnombreense. Orthohantavirus sinnombreense is classified in the genus Orthohantavirus, which is classified in the family Hantaviridae, the family that all hantaviruses belong to. Other member viruses of the species include Blue River virus, Convinct Creek 107 virus, and New York virus. The NM R11 isolate of Sin Nombre virus is the exemplar virus of the species.{{cite web|url=https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Undef&id=3052499&lvl=3&keep=1&srchmode=1&unlock

• Family: Hantaviridae
  • Genus: Orthohantavirus
    • Species: Orthohantavirus sinnombreense
      • Blue River virus, transmitted by the white-footed mouse (P. leucopus)
      • Convict Creek 107 virus, transmitted by the eastern deer mouse (P. maniculatus)
      • Monongahela virus, transmitted by the cloudland deer mouse (P. maniculatus nubiterrae), a subspecies of the eastern deer mouse
      • New York virus, transmitted by the white-footed mouse (P. leucopus)
      • Sin Nombre virus, transmitted by the western deer mouse (P. sonoriensis)
        • Four Corners virus, a name given to the virus, an isolate of SNV, that caused the 1993 Four Corners outbreak

History

In 1993, an outbreak of highly lethal acute respiratory distress syndrome caused by a novel hantavirus was discovered near the Cañon de la Muerte on the Navajo Reservation. The hantavirus was initially named the Muerto Canyon hantavirus, in keeping with the convention for naming new pathogens after the site of the first reported infection. Due to the perceived stigma, the Navajo Nation objected to the name. As the virus was discovered in the Four Corners region, the virologists then tried calling it the "Four Corners virus", but local residents raised similar objections. The exasperated researchers named it the Sin Nombre virus, meaning "the virus without a name."

Hantavirus pulmonary syndrome, the disease caused by New World hantaviruses such as the Sin Nombre virus, was previously unknown. In 2012, an outbreak of Sin Nombre virus in Yosemite National Park infected ten tourists with HPS, resulting in three fatalities.

Notes

References

References

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