Sin Nombre virus

Sin Nombre virus (SNV) is the most common cause of hantavirus pulmonary syndrome (HPS) in North America. Sin Nombre virus is transmitted mainly by the western deer mouse (Peromyscus sonoriensis). In its natural reservoir, SNV causes an asymptomatic, persistent 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 leads to HPS, an illness characterized by an early phase of mild and moderate symptoms such as fever, headache, and fatigue, followed by sudden respiratory failure. The case fatality rate from infection is 30 to 50 percent.

The genome of SNV is about 12.3 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.

SNV replicates first by binding to the surface of cells with its envelope spikes. Virus particles, called virions, are then taken into the cell by endosomes, 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 near the cell membrane, where virions bud from the cell membrane and use it to obtain their viral envelope and leave the cell.

SNV was first discovered in 1993 when it caused an outbreak of disease in the Four Corners region of the US. This outbreak was historically significant since it marked the first time that pathogenic hantaviruses were discovered in the Americas as well as the discovery of HPS. Since its discovery, SNV has caused hundreds of cases of HPS in the US and Canada, where it is responsible for most HPS cases. Most cases of HPS caused by SNV occur in the western parts of the US and Canada.

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.<ref name=ortho >{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> 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.<ref name=jacob >Template:Cite journal</ref><ref name=chen >Template:Cite journal</ref> The ends of each segment contain untranslated terminal regions (UTRs) that are involved in the replication and transcription of the genome.<ref name=chen /><ref name=tariq >Template:Cite journal</ref>

Structure

File:Sin Nombre hanta virus TEM PHIL 1136 lores.jpg

Transmission electron micrograph of Sin Nombre virus

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.<ref name=ortho /><ref name=jacob /> 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.<ref name=jacob />

Life cycle

SNV primarily infects endothelial cells and macrophages.<ref name=chen /> It enters cells by using β3-integrins as receptors. Virions are taken into a cell via an endosome. Once pH is lowered, the viral envelope fuses with the endosome, which releases viral RNA into the host cell's cytoplasm. The small segment is transcribed by RdRp first, then the medium segment, and lastly the large segment. Once the genome has been transcribed, RdRp snatches caps from host messenger RNA (mRNA) to create viral mRNA that is primed for translation by host ribosomes to produce viral proteins.<ref name=jacob /><ref name=dsouza >Template:Cite journal</ref>

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.<ref name=chen /> 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.<ref name=jacob /> Spike proteins are expressed on the surface of the cell membrane. Viral RNPs are transmitted to the cell membrane where they bud from the surface, thereby obtaining their envelope as the new progeny virions leave the cell.<ref name=dsouza /><ref name=koehler >Template:Cite journal</ref>

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.<ref name=chen /> Diploid progeny are also possible, in which virions may possess two of the same segment from two parent viruses.<ref name=klempa >Template:Cite journal</ref>

Ecology

File:Deer Mouse in Tree (6438329699).jpg

The western deer mouse, the natural reservoir of Sin Nombre virusTemplate:Refn

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.<ref name=jacob /> 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.<ref name=finkbeiner /> P. sonoriensis mainly lives in rural areas, which mirrors where HPS cases typically occur.<ref name=jacob />

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.<ref name=jacob /><ref name=tariq /> 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.<ref name=chen />

Disease

{{#invoke:Labelled list hatnote|labelledList|Main article|Main articles|Main page|Main pages}} 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.<ref name=jacob /><ref name=chen /> The case fatality rate from SNV infection is 30–50%.<ref name=chen />

SNV is the most common cause of HPS in the North America,<ref name=chen /> and since its discovery there have been more than 700 identified cases in the US<ref name=jacob /> and more than 100 cases in Canada.<ref name=warner >Template:Cite journal</ref> In the US and Canada, most cases occur in the west.<ref name=warner /> SNV 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 supplementing oxygen during the cardiopulmonary phase. No vaccines exist for Sin Nombre virus infection, so the main way to prevent infection is to avoid or minimize contact with rodents.<ref name=jacob /><ref name=chen /><ref name=warner /> Repeated infections of hantaviruses have not been observed, so recovering from infection likely grants life-long immunity.<ref name=hansen >Template:Cite journal</ref><ref name=kruger2011 >Template:Cite journal</ref>

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.<ref name=ncbimembers >{{#invoke:citation/CS1|citation |CitationClass=web }}</ref><ref name=bradfute >Template:Cite journal</ref> This taxonomy is shown as follows hereafter:<ref name=ictvhistory /><ref name=ortho /><ref name=ncbimembers /><ref name=bradfute />

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

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.<ref>Template:Cite journal</ref> Due to the perceived stigma, the Navajo Nation objected to the name.<ref>Template:Cite news</ref> 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.<ref name="isbn0-12-673050-4">Template:Cite book</ref> 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.<ref name="jacob" /><ref name="kuhn">Template:Cite journal</ref> In 2012, an outbreak of Sin Nombre virus in Yosemite National Park infected ten tourists with HPS, resulting in three fatalities.<ref name="jacob" /><ref name="mather">Template:Cite news</ref><ref name="Borowski">{{#invoke:citation/CS1|citation |CitationClass=web }}</ref>

External links

• Virology - CDC Hantaviruses
• Clinical and Lab Recognition and other info