Puumala hantavirus genome in patients with nephropathia epidemica: correlation of PCR positivity with HLA haplotype and link to viral sequences in local rodents

Abstract

Reverse transcription-PCR was used to analyze specimens from 20 Finnish nephropathia epidemica (NE) patients hospitalized during the period from October 1994 to January 1995. Blood and/or urine sediment specimens from seven patients were found to be positive for the genome sequences of Puumala hantavirus (PUU). PCR positivity of the specimens from the patients correlated well with the HLA-DRB1*0301 and HLA B8 alleles, which previously were shown to associate with severe courses of NE. Genetic analysis of the partial M-and/or S-segment sequences obtained from three severely ill NE patients revealed three PUU strains related to but distinct from previously reported strains from Finland. The M-segment sequence of PUU from bank voles trapped near the probable site of infection for one of the patients showed 98.2% identity to that of the PUU strain obtained from the patient, suggesting a link between wild-type PUU from the natural focus and the NE case. The S-segment sequences from the patient and the bank voles, however, showed substantially lower identity (95.8%). As this difference in diversity for M and S genes (1.8 and 4.2%) is atypical for PUU genetic drift, one possibility is that the strain acquired at the putative place of infection is a reassortant one.

Spatiotemporal dynamics of Puumala hantavirus associated with its rodent host, Myodes glareolus

“…The absence of any evidence of reassortment in our German populations over eight years, though, raises the question whether the frequency of multiple infections and/or reassortments differs between populations or geographical regions stochastically or whether this is related to environmental factors. At present, it appears that northern European PUUV strains might have higher evolutionary potential than central European ones because reassortment has been reported more often from northerly regions (Plyusnin et al 1997;Razzauti et al 2008Razzauti et al , 2013. However, the more frequent use of sequence data in Fennoscandia may bias the reports of reassortants in the literature.…”

Recent Advances in Hantavirus Molecular Biology and Disease

“…The glycoprotein precursor is intrinsically cleaved at a highly conserved amino acid motif, WAASA, generating two glycoproteins, Gn and Gc, respectively (Lober et al, 2001;Ruusala et al, 1992;Spiropoulou, 2001). After glycosylation in the ER, both Gn and Gc are transported to the Golgi complex, laying the foundations for final destinations where virions are maturated (Antic et al, 1992a;Plyusnin et al, 1997;Ravkov et al, 1998;Ruusala et al, 1992). After initial rounds of transcription, viral RdRp switches to the replication mode and generates three viral genomic RNAs, which are encapsidated by the viral N protein to form three nucleocapsids.…”

“…Therefore, it is considered as the most predominant viral antigen in the serologic response to infection. Hantaviral N protein has a molecular mass of approximately 50 kDa and contains 429-433 amino acid residues (de Carvalho Nicacio et al, 2001;Plyusnin et al, 1997;Van Epps et al, 1999). It is highly conserved across hantaviruses and contains cross-reactive epitopes that encompass the first 100 amino acids at N-terminal (Elgh et al, 1996;Gott et al, 1997;Schmaljohn et al, 1986Schmaljohn et al, , 1987Yamada et al, 1995).…”

“…RNA viruses employ several mechanisms to generate useful variations and to edit deleterious ones, which include reassortment and recombination (Barr and Fearns, 2010). Natural reassortment has been detected among hantaviruses (Henderson et al, 1995;Li et al, 1995;Plyusnin et al, 1997), and several experimental reassortants have been generated in the laboratory by infecting different strains of the same hantavirus (Ebihara et al, 2000;Rodriguez et al, 1998). Recently, Handke et al were able to generate in vitro reassortants between pathogenic PUUV and nonpathogenic PHV (Handke et al, 2010).…”

Dobrava, but not Saaremaa, hantavirus is lethal and induces nitric oxide production in suckling mice

“…Reverse transcription polymerase chain reaction (RT-PCR) and nested PCR of nt 389e741 of DOBV/SAAV S segment were performed essentially as described earlier [46] on experimentally infected animals. RNA was extracted using TriPure as described by the manufacturer (Roche Diagnostics).…”