Molecular characterization of very virulent infectious bursal disease virus strains circulating in Egypt from 2003 to 2014

This review is focused on the acute form of infectious bursal disease (IBD) caused by very virulent IBD virus (vvIBDV). First described in Europe about 10 years ago, this new form of the disease has rapidly spread all over the world, causing dramatic losses; after a decade, it still represents a considerable threat to the poultry industry. Emergence of the acute forms of the disease has drastically changed the epidemiology of IBD. Although their origin is still under investigation, vvIBDVs have spread all over the world in a very explosive but conserved manner. This raises the question of the origin of vvIBDVs, of the possible existence of reservoirs and of the possible emergence of new, distinct lineages in the future. While it has become clear that amino acids within the variable region of virus protein VP2 account for the molecular basis of antigenic variation, no definite hot spot that determines pathogenicity has been identified. Fingerprints of VP2 on vvIBDVs have to be considered more as common evolutionary markers than as virulence markers. The search for such markers is in progress. Pathogenesis of the disease is still poorly understood, and cytokines might play a crucial role in the onset of the disease and in the development of immunosuppression. Mechanisms such as apoptosis and necrosis have been described in lymphoid organs and are involved in the severity of the disease. Macrophages, especially, could play a specific role in the acute phase. Classical serotype 1 vaccines still induce good protection, but the actual problem for control of the disease has became the interference of maternally derived antibody in the establishment of the vaccination schedule. The development of safe vaccines that could either transmit a high passive immunity which could protect broilers during the whole growing period or prime an immune response before or at hatching in the presence of passive immunity might be established in the near future. In this context, recombinant vaccines and virus-neutralizing factor technology might have an advantage over other approaches.

It is widely assumed that new proteins are created by duplication, fusion, or fission of existing coding sequences. Another mechanism of protein birth is provided by overlapping genes. They are created de novo by mutations within a coding sequence that lead to the expression of a novel protein in another reading frame, a process called "overprinting." To investigate this mechanism, we have analyzed the sequences of the protein products of manually curated overlapping genes from 43 genera of unspliced RNA viruses infecting eukaryotes. Overlapping proteins have a sequence composition globally biased toward disorder-promoting amino acids and are predicted to contain significantly more structural disorder than nonoverlapping proteins. By analyzing the phylogenetic distribution of overlapping proteins, we were able to confirm that 17 of these had been created de novo and to study them individually. Most proteins created de novo are orphans (i.e., restricted to one species or genus). Almost all are accessory proteins that play a role in viral pathogenicity or spread, rather than proteins central to viral replication or structure. Most proteins created de novo are predicted to be fully disordered and have a highly unusual sequence composition. This suggests that some viral overlapping reading frames encoding hypothetical proteins with highly biased composition, often discarded as noncoding, might in fact encode proteins. Some proteins created de novo are predicted to be ordered, however, and whenever a three-dimensional structure of such a protein has been solved, it corresponds to a fold previously unobserved, suggesting that the study of these proteins could enhance our knowledge of protein space.

Infectious bursal disease (IBD) virus (IBDV) is the etiological agent of "Gumboro disease". Although first observed about 40 years ago, this disease continues to pose an important threat to the commercial poultry industry. The emergence of antigenic variant as well as very virulent strains in vaccinated flocks considerably stimulated research efforts on both, IBD and IBDV. In this review, some of the recent advances in the understanding of the structure, morphogenesis and molecular biology of the virus as well as in development of new diagnostic approaches and new strategies for vaccination against IBD are briefly summarized.