Phylogenetic Analysis Reveals a Correlation between the Expansion of Very Virulent Infectious Bursal Disease Virus and Reassortment of Its Genome Segment B

Abstract

Infectious bursal disease virus (IBDV) is a birnavirus causing immunosuppressive disease in chickens.Emergence of the very virulent form of IBDV (vvIBDV) in the late 1980s dramatically changed the epidemiology of the disease. In this study, we investigated the phylogenetic origins of its genome segments and estimated the time of emergence of their most recent common ancestors. Moreover, with recently developed coalescence techniques, we reconstructed the past population dynamics of vvIBDV and timed the onset of its expansion to the late 1980s. Our analysis suggests that genome segment A of vvIBDV emerged at least 20 years before its expansion, which argues against the hypothesis that mutation of genome segment A is the major contributing factor in the emergence and expansion of vvIBDV. Alternatively, the phylogeny of genome segment B suggests a possible reassortment event estimated to have taken place around the mid-1980s, which seems to coincide with its expansion within approximately 5 years. We therefore hypothesize that the reassortment of genome segment B initiated vvIBDV expansion in the late 1980s, possibly by enhancing the virulence of the virus synergistically with its existing genome segment A. This report reveals the possible mechanisms leading to the emergence and expansion of vvIBDV, which would certainly provide insights into the scope of surveillance and prevention efforts regarding the disease.Infectious bursal disease (IBD) is an immunosuppressive disease of young chickens that causes considerable economic loss to the poultry industry worldwide. The causative agent of IBD is a bisegmented, double-stranded RNA virus of the Birnaviridae family named IBD virus (IBDV). IBD was firstly reported in 1957 in broilers of the Delmarva Peninsula of the United States. It had spread rapidly throughout the United States by 1965 but was effectively controlled by vaccinations in the mid-1970s (23). In 1986, vaccination failures were reported and IBDV isolates with enhanced virulence were identified and characterized (18). These new isolates, named very virulent IBDV (vvIBDV), were then described by Chettle and coworkers (4) as the causative agents of the first reported cases of severe and acute IBD in Europe. These very virulent strains have rapidly spread all over Asia and other parts of the world (11) in an explosive manner (42), following their introduction into Japan in the early 1990s (30).The epidemiological event leading to the emergence and expansion of vvIBDV is an open question. Phylogenetic analyses have revealed independent evolutionary histories of the two genome segments (17, 44), suggesting that a reassortment event may have played a role in the emergence of vvIBDV. Previous reports suggested that both the major capsid protein (VP2) and the RNA-dependent RNA polymerase (VP1), which are located on genome segments A and B, respectively, contribute to the virulence of IBDV (1-3, 26, 43). Questions have been raised regarding the phylogenetic origins and roles of the unique mutations of the two genome...

Both Genome Segments Contribute to the Pathogenicity of Very Virulent Infectious Bursal Disease Virus

“…The current study demonstrates that both genomic segments of 94432, both of which are phylogenetically related to those of vvIBDVs, do contribute to pathogenicity. This primary contribution of VP1 to the pathogenicity of vvIBDV is consistent with the findings of a chronophylogenetic study suggesting that vvIBDV expansion was almost concomitant with the emergence of the typical vvIBDV-like segment B (38).…”

“…VP2 is, however, unlikely to be the only factor for virulence: laboratory-engineered reassortant viruses derived from vvIBDV exhibited delayed replication in the bursa (37) or failed to induce morbidity and mortality (31) unless they also had a typical vvIBDV-related segment B. This observation is consistent with the phylogeny-based hypothesis that both genome segments may be involved in the emergence of vvIBDV (38,39). Recently, this hypothesis was substantiated by the isolation of three naturally occurring segment B-reassorted vvIBDV isolates, all with reduced pathogenicity in chickens (40,41).…”

Complete Genome Sequence Analysis of a Natural Reassortant Infectious Bursal Disease Virus in China

“…The genome of IBDV is a bisegmented doublestranded RNA consisting of 2 segments (A and B); segment A encodes VP5 and polyprotein (VP2-VP4-VP3), while segment B encodes VP1 protein (5). The coinfection with very virulent IBDV (vvIBDV) and attenuated IBDV strains led to exchange of the double-stranded genomic RNA segments to generate new reassortant viruses (2,3,11).…”

Genetic characterization of South American infectious bursal disease virus reveals the existence of a distinct worldwide-spread genetic lineage

“…Genetic analyses revealed that these IBDV strains have nucleotide and amino acid signatures and constitute well-supported independent clades in phylogenetic trees (Boot et al, 2000;van den Berg, 2000;Le Nouën et al, 2005;Hon et al, 2006). Besides the three lineages corresponding to c, va and vv strains, phylogenetic trees also resolve an independent lineage for the ca strains that comprise vaccine strains maintained in the laboratory and vaccine-like virus collected from the field (Kim et al, 2010).…”

“…By studying both segments, it is possible to analyse their coevolution, to detect the occurrence of natural reassortants and to determine the role of VP1 in pathogenicity (Le Nouën et al, 2006;Escaffre et al, 2013). VP1 phylogeny resolves a lineage corresponding to the vvIBDV strain and a nonvvIBDV clade constituted by the remaining strains and serotype 2 viruses (Hon et al, 2006).…”