Andes virus

The genome of ANDV is about 12.1 thousand nucleotides in length and segmented into three negative-sense, single-stranded RNA (-ssRNA) segments. The segments form into circles via non-covalent bonding of the ends of the genome.^[7] 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 an 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.^[3][8]

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.^[7][9]

Andes virus primarily infects endothelial cells and macrophages.^[3] It enters cells by using β3-integrins as receptors.^[9] 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.^[9][10]

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.^[3] 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.^[9] 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.^[10][11]

The most common way that hantaviruses evolve is through mutations of individual nucleotides being inserted, deleted, or substituted. Because ANDV 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.^[3]

Andes virus is carried mainly by the long-tailed pygmy rice rat (Oligoryzomys longicaudatus),^[3][9] a common species in rural Argentina and Chile.^[12] Apart from the long-tailed pygmy rice rat, ANDV (Andes Virus) is relatively common in the long-haired grass mouse.^[13] Seroprevalence of ANDV in its hosts is found throughout South America, but is highest in Patagonia.^[10] Transmission of ANDV between rodents appears to be primarily through saliva and aerosols that contain saliva. In its rodent hosts, it causes a persistent, asymptomatic infection.^[14] Transmission to humans occurs mainly through the inhalation of aerosols that contain mouse salivas, urine, or feces.^[8][9] Inhaling those aerosols requires the disease to become airborne. This mostly occurs when rodent discharge is disturbed (e.g., vacuums, sweeping).^[15] Transmission can also occur through consumption of contaminated food, bites, and scratches.^[3]

Andes virus is the only hantavirus known to be transmitted from person to person.^[16] Human-to-human transmission was first identified during a 1996 outbreak in southern Argentina, and sustained generational transmission was subsequently documented during the 2018–2019 Epuyén outbreak.^[17] The virus transmits through direct physical contact, saliva, airborne droplets, breastmilk, from mother to child across the placenta, and through the digestive tract.^[3][10] This transmission primarily occurs among family members or during prolonged close contact with an infected individual in the prodromal phase of the disease.^[16][10]

It is theorized that when rodent populations undergo a significant increase in individual numbers (outbreaks), an increase in rodent-human contact possibilities could also increase.  Rodent outbreaks in Argentina and Chile are known to occur as a result of increases in rainfall associated with the El Niño phenomenon, which provide beneficial environmental conditions for rodents that host ANDV (food, water, cover).^[18]  Cyclical flowering and seeding of chusquea grasses (Chusquea spp.), which supply large quantities of seeds, is also considered an important environmental factor (food) for rodent outbreaks in these areas.^[19]  These are large environmental changes of limited duration that are well-correlated with increased recruitment (birth, survival) of rodents.^[20]  High populations of rodents are evident by the autumn as abundant numbers of rodents are noted to move into forested areas for the autumn and winter seasons. However, it is usually not until the following spring and summer that ANDV transmission from rodents to humans becomes evident.  This likely occurs as rodent activities shift from forested areas to open habitat in order to reproduce and to seek additional food supplies^[20], thereby increasing the possibility of rodent-human contact.  Epidemiological research links human exposure to hantavirus due to an increase in human outdoor activities during the spring and summer months (recreation, agricultural and forestry work, military exercises) in areas where rodent activities are concentrated.^[21]

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.^[3][9] The case fatality rate from ANDV infection is about 40% (as of 2023).^[3]

Andes virus typically causes disease in Argentina and Chile.^[9] In Chile the first HPS case was detected in 1995 and the first known outbreak was noted in 1997 in Coyhaique.^[5] Revision of older cases show that the first known case may actually have occurred in 1993.^[5] In Argentina, 1,350 cases of HPS have occurred up to 2016 (from various hantaviruses).^[22] It is estimated that about 16% of these cases were due to ANDV.^[23] At least another 34 cases of ANDV occurred in late 2018 and early 2019 in Argentina.^[17]

Andes virus infection is diagnosed based on symptoms and testing for hantavirus nucleic acid, proteins, or hantavirus-specific antibodies.

Repeated infections of hantaviruses have not been observed, so recovering from infection may grant immunity.^[24][25]

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 ANDV is the exemplar virus of the species. This taxonomy is shown hereafter:^{[2][7][26][27]}

• Family: Hantaviridae
  • Genus: Orthohantavirus
    • Species: Orthohantavirus andesense
      • Andes virus
      • Castelo dos Sonhos virus
      • Lechiguanas virus
      • Orán virus

Clades include

• ANDV South (ANDV Sout),^[48][49] and
• ANDV (C-I)^[50]

Lineages that have been proposed, include

• ANDV Cent BsAs,^[51] or "Central Buenos Aires"^[52] lineage
• ANDV Cent Plata,^[51] or "Central Plata"^[52] lineage
• ANDV Cent Lec;^[51] A media outlet said in 2023, that proposed lineages include "Central Lechiguanas, North, and South".^[52]

• Scrub typhus, a disease reported in southernmost Chile as early as 2020
• Hantavirus pulmonary syndrome
• Sin Nombre virus (the other common hantavirus species)
• MV Hondius hantavirus outbreak