Genetic reassortment between high-virulent and low-virulent Dobrava-Belgrade virus strains

Abstract

The tri-segmented RNA genome of hantaviruses facilitates genetic reassortment by segment swapping when cells are co-infected with different virus strains. We found efficient in vitro reassortment between members of two different genetic lineages of the Dobrava-Belgrade virus species, the weakly virulent DOBV-Aa and highly virulent DOBV-Af. In all reassortants, S and L segments originated from the same parental strain, and only the M segment was exchanged. To identify functional differences between the parental strains DOBV-Aa and DOBV-Af in cell culture and to compare them with the reassortants, we studied elements of the innate immunity in virus-infected cells. The contrasting phenotypes of the parental viruses were maintained by the reassortants carrying the respective S and L segments of the parental virus and were not influenced by the origin of the M segment.

Dynamic Circulation and Genetic Exchange of a Shrew-borne Hantavirus, Imjin virus, in the Republic of Korea

“…We observed the L segment reassortant and S segment recombinant of HTNV infected humans and caused HFRS, respectively28. Dobrava-Belgrade virus (DOBV) showed the reassortment of M segment between avirulent strain DOBV-Aa and virulent strain DOBV-Af in vitro 57. Thus, further studies are required to understand the biological and ecological consequences of recombination or reassortment in the MJNV population.…”

Clinical characterization of two severe cases of hemorrhagic fever with renal syndrome (HFRS) caused by hantaviruses Puumala and Dobrava-Belgrade genotype Sochi

“…Host- and virus-specific determinants are discussed as reasons for the broad range of clinical pictures [1–5]. The most obvious differences exist between the clinical picture of hantaviral cardiopulmonary syndrome (HCPS) and HFRS caused by New and Old World hantaviruses, respectively [6].…”

“…Differences in the use of entry receptors, in the regulation of cytokine response and in viral replication were described to be associated with pathogenicity [8–11]. Studies with genetic reassortants in vitro and in animal models suggest molecular determinants to be responsible for virulence [5, 12]. However, the species-specific factors of hantaviruses that are responsible for pathogenicity and clinical picture are not identified so far.…”

Dobrava-Belgrade Hantavirus from Germany Shows Receptor Usage and Innate Immunity Induction Consistent with the Pathogenicity of the Virus in Humans

“…A readout marker for IFN bioactivity, which has been often used in characterization of hantaviruses, is the antiviral MxA protein [21]–[25]. The MxA protein belongs to the superfamily of dynamin-like GTPases and is involved in mediation of antiviral immune response against many viruses [26].…”

“…Hantaviruses are weak inducers of type I (α/β) interferon, however, a recent study revealed that hantaviruses are able to induce type III IFN (λ1–3) in type I IFN-deficient Vero E6 cells which are routinely used for generation of hantavirus stocks [30]. Therefore, influence of Vero E6-derived type III IFN on earlier observed DOBV MxA induction patterns [25] has to be investigated.…”