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. 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

thumb|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.

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

thumb|The western deer mouse, the natural reservoir of Sin Nombre virus

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. 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. This taxonomy is shown as follows hereafter:

  • 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

History

thumb|alt=A photograph of tent cabins in Curry Village in Yosemite National Park, California|Tent cabins in [[Curry Village in Yosemite National Park, California. A small outbreak of HPS caused by SNV occurred in the park in 2012, mainly at Curry Village, during which ten visitors were infected and three died.]]

In 1993, an outbreak of highly lethal acute respiratory distress syndrome occurred in the Four Corners region of the United States. This outbreak was determined to be caused by a novel hantavirus, initially named Four Corners virus, which was later rejected because of the negative association with the region. In January 1994, the virus was given the name Muerto Canyon virus after a location near where the disease was first observed. This was opposed by locals, who did not want to be associated with the virus, so a new name was sought. Convict Creek virus was proposed, named after where the mouse used to culture the virus was captured, but this was also rejected.