# Andes virus

Andes virus (ANDV) is the most common cause of hantavirus pulmonary syndrome (HPS) in South America. Andes virus is transmitted mainly by the long-tailed pygmy rice rat (Oligoryzomys longicaudatus). In its natural reservoir, ANDV 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 high, at about 40%.
The genome of ANDV is about 12.1 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.
ANDV 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.
ANDV was first discovered in 1995 in Argentina and in Chile later that year. More than a hundred cases of HPS caused by Andes virus occur each year, most of them in Argentina and Chile. Apart from the long-tailed pygmy rice rat, Andes virus has also been found in various other rodent species in South America, most commonly the long-haired grass mouse (Abrothrix longipilis). Human-to-human transmission of ANDV was first reported in 1996 and continual reports since then have been made that Andes virus can spread from person to person. There is, however, insufficient evidence of such transmission.

## Genome

The genome of Andes virus is about 12.1 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 1.87 kilobases (kb) in length, encodes the viral nucleoprotein and a non-structural protein that inhibits interferon production. The medium segment, about 3.67 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 and range from 80 to 160 nm in diameter. 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.

## Life cycle

ANDV primarily infects endothelial cells and macrophages. 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.
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. 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. 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.

## Evolution

The most common way that hantaviruses evolve is through mutations of individual nucleotides being inserted, deleted, or substituted. Because Andes 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.

## Ecology

Andes virus is carried mainly by the long-tailed pygmy rice rat (Oligoryzomys longicaudatus), a common species in rural Argentina and Chile. Apart from the long-tailed pygmy rice rat, Andes virus is relatively common in the long-haired grass mouse. Seroprevalence of ANDV in its hosts is found throughout South America, but is highest in Patagonia. Transmission of Andes virus between rodents appears to be primarily through saliva and aerosols that contain saliva. In its rodent hosts, it causes a persistent, asymptomatic infection. Transmission to humans occurs mainly through the inhalation of aerosols that contain mouse salivas, urine, or feces. Transmission can also occur through consumption of contaminated food, bites, and scratches.
Human-to-human transmission of Andes virus was first claimed to be a part of a 1996 outbreak in southern Argentina. Since then, there have been continual claims that it can spread from person to person. It can reportedly spread through saliva, airborne droplets from coughing or sneezing, breastmilk, from mother to child across the placenta, and through the digestive tract. Person-to-person transmission reportedly occurs mainly within families or when engaging in close activities with an infected person during the prodromal disease phase. A 2021 systematic review, however, found these claims not to be supported by sufficient evidence and cited flawed methodology in research on Andes virus outbreaks.

## Disease

Andes 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 (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 ANDV infection is about 40%.
ANDV is the most common cause of HPS in South America, which predominantly occurs in Argentina, Brazil, and Chile. In Argentina, 100–200 cases occur each year. ANDV 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 Andes virus infection, so the main way to prevent infection is to avoid or minimize contact with rodents. Repeated infections of hantaviruses have not been observed, so recovering from infection likely grants life-long immunity.

## Classification

Andes virus is classified into the species Orthohantavirus andesense in the genus Orthohantavirus, which is in the family Hantaviridae, the family that all hantaviruses belong to. Other member viruses of Orthohantavirus andesense include the Castelo dos Sonhos virus, Lechiguanas virus, and Orán virus. The Chile-9717869 isolate of Andes virus is the exemplar virus of the species. This taxonomy is shown hereafter:
* Family: Hantaviridae
** Genus: Orthohantavirus
*** Species Orthohantavirus andesense
**** Andes virus
**** Castelo dos Sonhos virus
**** Lechiguanas virus
**** Orán virus

## History

Andes virus was first discovered in Argentina in 1995 and is named after the Andes mountain range. Cases were first reported in Chile that same year. Human-to-human transmission was first reported in an outbreak in 1996 in El Bolsón, Argentina. Since then, sporadic outbreaks with reported person-to-person transmission have occurred. Andes virus was accepted as a species by the International Committee on Taxonomy of Viruses in 1999 and has undergone a series of changes to its species name, first changing to Andes hantavirus, then Andes orthohantavirus, and most recently to the current Orthohantavirus andesense.