Puumala virus

Genome

The genome of Puumala virus is about 12 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 1.83 kilobases (kb) in length,

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

PUUV 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 complementary strand. Progeny RNA strands are then encapsidated by nucleoproteins.

Diversity

There are eight lineages of PUUV: Central European, Alpe-Adrian, Danish, South-Scandinavian, North-Scandinavian, Finnish, Russian, and Latvian. These lineages likely emerged from isolation of bank voles in glacial refuges during the last glacial period, 28–23 thousand years ago. After the last glacial period, bank voles recolonized much of Eurasia and carried the different lineages with them.

Evolution

The most common way that hantaviruses evolve is through mutations of individual nucleotides being inserted, deleted, or substituted. Because Puumala 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. The M segment of the genome is the segment most commonly involved in reassortment.

Ecology

Puumala virus is carried by bank voles (Clethrionomys glareolus), found throughout Europe and Russia.

In its natural reservoir, PUUV causes a persistent and mainly asymptomatic infection. Wild bank voles shed the virus for the rest of their life after they become infected. High levels of maternal antibodies in newborns may delay the time at which they get infected, which indirectly delays the incidence of human infections in various years. Bank voles infected with PUUV have a lower winter survival rate than uninfected ones, possibly due to effects on metabolism. PUUV infection also affects the body condition of the mother, which affects the body condition of offspring. Transmission of Puumala virus occurs through inhalation of aerosols that contain saliva, urine, or feces, as well as through contaminated food, bites, and physical contact with bank vole excretions. Antibodies to Puumala virus have been detected in cattle, deer, and rabbits, but the role of these animals as hosts is unknown.

Disease

Main article: Hantavirus hemorrhagic fever with renal syndrome

Puumala virus infection is subclinical 70–80% of the time, with no apparent symptoms. When symptoms appear, PUUV usually causes a mild form of hemorrhagic fever with renal syndrome (HFRS) often called nephropathia epidemica (NE). after exposure and come in five phases: fever, hypotension, low urine production, high urine production, then recovery. HFRS is hallmarked by acute kidney disease with kidney swelling, excess protein in urine, and blood in urine. Early symptoms include fever, headache, lower back pain, nausea, vomiting, diarrhea, bloody stool, and the appearance of spots on the skin. During the hypotensive phase, there is a sudden lowering of blood pressure and shock due to microvascular leakage. Low urine production then occurs as a result of renal failure. As renal function recovers, urine production increases. In more mild cases, the different phases of illness may be hard to distinguish, or some phases may be absent, while in more severe cases, the phases may overlap.

PUUV infection is mainly observed in northern and central Europe Symptoms are less severe in children than in adults. and in Turkey.

PUUV infection is diagnosed based on observation of symptoms and testing for hantavirus nucleic acid, proteins, or hantavirus-specific antibodies. No vaccines exist to protect against Puumala virus infection;

Classification

Puumala virus is classified into the species Orthohantavirus puumalaense in the genus Orthohantavirus, which is in the family Hantaviridae, the family that all hantaviruses belong to. Other members of Orthohantavirus puumalaense include Hokkaido virus and Muju virus. The CG1820 isolate of Puumala virus is the exemplar virus of the species. This taxonomy is shown hereafter:

• Family: Hantaviridae
  • Genus: Orthohantavirus
    • Species: Orthohantavirus puumalaense
      • Hokkaido virus, found in grey red-backed voles (Craseomys rufocanus) in Hokkaido, Japan and Siberia, Russia and in northern red-backed voles (Clethrionomys rutilus) in Siberia, Russia
      • Muju virus, found in royal voles (Craseomys regulus) in South Korea
      • Puumala virus

History

In 1942, an epidemic of disease occurred among soldiers in Salla, Eastern Lapland, Finland during the Second World War. Around 1,000 German and 60 Finnish soldiers were affected. Symptoms included fever, headache, abdominal pain, back pain, nausea, and vomiting. Notably, temporarily impaired vision was noted in many patients, as were increased protein in urine, blood in urine, and reduced renal function. The novel disease was named "nephropathia epidemica". Reports at the time suspected leptospirosis and noted that it could not spread from person to person. No cases during the outbreak resulted in death. Both bank voles and Norway lemmings were suspected as having caused the epidemic, but hantaviruses have not been discovered in Norway lemmings, which left just the bank vole, and thus Puumala virus, as likely responsible for the Salla epidemic. Another epidemic occurred in 1995 in Croatia during the Balkan Wars. As with the 1942 epidemic, the outbreak mainly occurred in soldiers who lived in poor conditions such as trenches and wooden huts in forests. This exposed them to rodents that carried the virus. In addition to PUUV, Dobrava virus was also responsible for the 1995 epidemic.

In 1980, Markus Brummer-Korvenkontio and Antti Vaheri tested for hantavirus infection in the lung tissue of bank voles using immunofluorescent antibody tests, a method similar to what was used to discover the first hantavirus, Hantaan virus. Subsequent testing of the Finnish population showed that many Finns had been infected with the virus. Two names were considered for this newly discovered virus, both names of Finnish municipalities: Puumala and Pieksämäki, the former of which was chosen since the latter would be more difficult for English speakers to pronounce. Puumala virus was accepted as a species by the International Committee on Taxonomy of Viruses in 1987 and has undergone a series of changes to its species name, first changing to Puumala hantavirus, then Puumala orthohantavirus, and most recently to the current Orthohantavirus puumalaense.

References

References

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