Molecular Evolution of Puumala Hantavirus

Abstract

Puumala virus (PUUV) is a negative-stranded RNA virus in the genus Hantavirus, family Bunyaviridae. In this study, detailed phylogenetic analysis was performed on 42 complete S segment sequences of PUUV originated from several European countries, Russia, and Japan, the largest set available thus far for hantaviruses. The results show that PUUV sequences form seven distinct and well-supported genetic lineages; within these lineages, geographical clustering of genetic variants is observed. The overall phylogeny of PUUV is star-like, suggesting an early split of genetic lineages. The individual PUUV lineages appear to be independent, with the only exception to this being the Finnish and the Russian lineages that are closely connected to each other. Two strains of PUUV-like virus from Japan form the most ancestral lineage diverging from PUUV. Recombination points within the S segment were searched for and evidence for intralineage recombination events was seen in the Finnish, Russian, Danish, and Belgian lineages of PUUV. Molecular clock analysis showed that PUUV is a stable virus, evolving slowly at a rate of 0.7 ؋ 10 ؊7 to 2.2 ؋ 10 ؊6 nt substitutions per site per year.Puumala virus (PUUV) belongs to the genus Hantavirus of the family Bunyaviridae (12). Like other members of this family, PUUV is an enveloped virus with a segmented, singlestranded RNA genome of negative polarity. The large (L) segment of 6.5 kb encodes the viral RNA polymerase, the 3.7-kb medium (M) segment encodes the two surface glycoproteins, and the 1.8-kb small (S) segment encodes the nucleocapsid protein (N).The natural host of PUUV is the bank vole, Clethrionomys glareolus, which belongs to the Arvicolinae subfamily of the Muridae family. The bank vole is found in most of Europe, excluding the Mediterranean coast and the northernmost areas ( Fig. 1) (40). The virus causes a life-long persistent and asymptomatic infection in rodents (47). In contrast, in humans PUUV is pathogenic, causing nephropathia epidemica, a mild form of hemorrhagic fever with renal syndrome (HFRS) (8).PUUV from the following countries has been genetically characterized ( Fig. 1): Finland (45,46,48,62), Sweden (24,25,38), Norway (38), Denmark (3), Russia (3,16,48,49,66), Belgium (6, 13), Austria (1, 5), and Germany (19, 43). So far, over 100 partial or complete PUUV sequences have been deposited in GenBank. These include 38 complete S segment sequences, 9 complete M segment sequences, and 2 complete L segment sequences. In general, the phylogenetic relationships between different hantaviruses and their rodent hosts mirror each other, supporting the idea of coevolution of the virus and its host (44). Furthermore, different strains of a given hantavirus type, including PUUV, show geographical clustering (48, 49) reflecting the sometime complicated history of host range movements. The most recent bank vole range changes are due to the recolonization of Europe and especially Fennoscandia after the last ice age 10,000 years ago (29). Earlier it has been shown that these migr...

Genetic similarity of Puumala viruses found in Finland and western Siberia and of the mitochondrial DNA of their rodent hosts suggests a common evolutionary origin

“…The Omsk samples had specific nucleocapsid (N) protein amino acid "signatures" (Sironen et al, 2001) that (Table 3). However, the M-segment sequences were closer to the Russian strains, Udmurtia and Kazan (83.2%), than to the Finnish strain Sotkamo (82.2%).…”

Analysis of Puumala hantavirus in a bank vole population in northern Finland: evidence for co-circulation of two genetic lineages and frequent reassortment between strains

“…In contrast, when the N sequences from the two groups were compared, 11 aa substitutions were observed, seven of which were conservative. Three of these 11 residues belonged to lineage-specific amino acid signatures (Sironen et al, 2001); they were found in genetic variants from the FIN (Met262, Asp304) and the N-SCA (Asp272) lineages. These findings suggested that the two genetic groups of Pallasjärvi PUUV sequences belonged to different genetic lineages: the FIN (genetic variants S1/S2) and the N-SCA (variants S3-S5) lineages.…”

“…There is also some evidence for genome reassortment (Plyusnin et al, 1997;Razzauti et al, 2008) and recombination (Sironen et al, 2001) in PUUV. The steady generation of mutant sequences during PUUV replication in an individual host results in a swarm of viral quasi-species (Plyusnin et al, 1995b), an ensemble of closely related sequences that cooperates in maintaining distinct features of a virus such as its transmissibility and pathogenicity (Domingo & Holland, 1997;Vignuzzi et al, 2006).…”

“…The steady generation of mutant sequences during PUUV replication in an individual host results in a swarm of viral quasi-species (Plyusnin et al, 1995b), an ensemble of closely related sequences that cooperates in maintaining distinct features of a virus such as its transmissibility and pathogenicity (Domingo & Holland, 1997;Vignuzzi et al, 2006). In general, PUUV evolution follows the neutral (or quasi-neutral) mode and the estimated evolution rate appears to be relatively low (Sironen et al, 2001).…”

“…Its range continues eastward into central Siberia (IUCN, 2007). Throughout its distribution, the genetic variants of PUUV show phylogeographical clustering (Plyusnin et al, 1994(Plyusnin et al, , 1995aHörling et al, 1996;Lundkvist et al, 1998;Asikainen et al, 2000;Sironen et al, 2001;Johansson et al, 2008). Bank voles recolonized Fennoscandia after the last glaciation period, 12 000-9000 years ago, from different directions (Fig.…”