Infectious bursal disease virus (IBDV)

Infectious bursal disease virus (IBDV), a member of the Birnaviridae family, infects chickens and is responsible for infectious bursal disease (IBD), also known as “Gumboro Disease”. The disease can manifest as ruffled feathers, depression, anorexia, diarrhoea and soiled vent feathers, and infection with very virulent strains can lead to mortality rates as high as 100%. The virus infects B cells, the majority of which reside in the bursa of Fabricius, leading to cell death that can result in immunosuppression. Consequently, birds that recover from IBDV infection are frequently more susceptible to secondary infections and respond less well to vaccination programmes. The economic significance is therefore twofold: a result of the morbidity and mortality caused by infection, and a result of secondary effects following immunosuppression. The virus is very resilient in the environment and is highly contagious. Classical strains of the virus have circulated since the 1960s, but the disease was adequately controlled by vaccination until the emergence of variant then very virulent strains in the 1980s made the task of controlling IBD more challenging. Despite a growing arsenal of vaccines, the infection remains enzootic worldwide, and still ranks among the top five infectious problems facing the poultry industry in almost all countries surveyed 1.


The first known outbreaks of IBD occurred in 1962 in Gumboro, Delaware, from where the disease gained its name. The virus was subsequently isolated 2 and termed IBDV in 1970 3. The disease was controlled by vaccination, however in 1985 variant (v) strains were first identified in the USA that were antigenically distinct from the classical strains 4,5 and, in 1986, very virulent (vv) strains emerged in Europe and subsequently spread to Africa, Asia, South America, and eventually the USA. 6.

The virus

IBDV belongs to the Birnaviridae family of viruses, characterised by a bi-segmented genome of double stranded (ds)RNA. IBDV is non-enveloped and possess a capsid of laevo icosahedral geometry with a T = 13 triangulation number that is formed of a single layer of protein and is 55-65nm in diameter. The two segments of the genome are designated Segment A and Segment B. Segment A encodes 4 proteins: VP5, VP2, VP4 and VP3. Segment B encodes 1 protein, VP1 7.

The VP1 protein is a non-canonical RNA dependent RNA polymerase, which is packaged into the virion as both a genome linked and a free protein 8,9. The VP2 protein forms 260 trimers that make up the capsid 7. The VP3 protein associates with the dsRNA genome, the VP1 polymerase, and the VP2 capsid 10, and has multiple functions in the infected cell: As well as forming a ribonucleoprotein (RNP) complex with the dsRNA genome and the VP1 protein, VP3 has been shown to upregulate VP1 polymerase activity 11, inhibit the activation of innate immune sensors such as MDA5 12, and inhibit PKR-mediated antiviral responses 13. VP4 is the viral protease that cleaves the polyprotein (see below) into its constitutive parts 14, and has also been shown to inhibit Type I IFN induction 15. VP5 is a non-structural protein that has a regulatory function in virus egress 16,17 and activates the PI3K/Akt signalling pathway in infected cells 18.

The viral replication cycle

Virus uptake into cells involves micropinocytosis and trafficking to early endosomes 19. As the endosome matures, the calcium concentration and pH decreases and a small 46 amino-acid amphipathic peptide, pep46, is released from the IBDV capsid. The peptide embeds in the endosomal membrane, forming pores of 2-10nm in diameter 20 which is too small for the virion to pass through but is large enough for molecules to enter the endosome, or for the RNP complex to be extruded into the cytoplasm.

Replication of the viral genome takes place in the cytoplasm, however our understanding of this process is incomplete. Genome replication occurs by strand displacement 9 and is independent of the VP2 capsid protein 21, suggesting that the presence of the RNP complex negates the necessity for a proteinaceous viral core for replication, in contrast to the dsRNA Reoviridae. VP3 has been shown to co-localise with vesicular structures bearing features of early and late endocytic compartments in the juxtanuclear region, even in cultures studied at 36 hours post-infection 22, implying that the virus may remodel cellular endosomal membranes to its advantage. Additionally, VP3-positive structures are associated with Golgi markers, implying this organelle may play a role in the assembly of progeny virions 22.

While Segment B is translated into a single functional protein, Segment A is synthesised as a polyprotein that is subsequently cleaved by the VP4 protease into its constitutive parts. Viral genomes are then packaged into daughter virions that form paracrystalline arrays in the cytoplasm of infected cells. Up to six populations of virus particles can be purified from infected cells that range from empty capsids to those containing up to 4 segments of dsRNA 23, providing evidence in favour of a random packaging model of encapsidation.

It is thought that the liberation of viable viral particles is predominantly dependent on cell lysis, although a non-lytic mechanism may also play a role in viral egress. The mechanism culminating in egress is an area of active research, and the VP5 protein has been shown to be required for efficient cell-cell spread 17.


The virus has a tropism for B lymphocytes, whereas T lymphocytes are not permissive to infection. The majority of B cells are located in the bursa of Fabricius (BF) in young birds, and this organ is the main site of viral replication and pathology during an infection. The virus is spread faeco-orally, and in one study where chickens were orally infected with a classical strain of IBDV, viral antigen was detected in macrophages and lymphoid cells in the caecum within 4 hours 24. Lymphoid cells in the duodenum and jejunum were subsequently infected 24, and within 24 hours there was histological evidence of infection in the BF 7. It is thought the virus disseminates from the gut to other tissues, including the BF, via the blood. However, the BF lumen is continuous with the gut lumen 25, and it is also possible that the virus can enter the organ directly across the epithelial cell lining.

Following infection of the BF, degeneration and necrosis of the B-cell follicles can be detected as early as one day post-infection, with associated infiltration of inflammatory cells such as heterophils. Haemorrhages are frequently observed, but not in every case. The weight of the BF has been shown to increase due to severe oedema, hyperaemia and accumulation of heterophils. As the inflammation subsides, there is necrosis and phagocytosis of heterophils and plasma cells, fibroplasia in the interfollicular connective tissue, and ultimately bursal atrophy 7.Consistent with the histological changes, there is an up-regulation of antiviral genes involved in the Type I IFN response, pro-apoptotic genes, and pro-inflammatory cytokines and chemokines, presumably from the infected B cell population. Additionally, there is an enhanced expression of genes associated with the activation of macrophages, T cells and NK cells 26.

Other organs may also show signs of pathological changes: the spleen may be enlarged, and there may be haemorrhages in the mucosa at the juncture of the proventriculus and ventriculus and in the thigh and breast muscles. Lesions in the caecal tonsils, thymus, spleen and bone marrow have also been observed in birds infected with vvIBDV, and the Harderian gland has been shown to be severely affected following infection of 1-day old chicks with IBDV 7.

As birds recover from infection, there is re-population of the BF with B lymphocytes, however, two distinct types of B-cell follicle have been observed: large follicles, most likely re-populated from endogenous bursal stem cells that survived IBDV infection, and small, poorly developed follicles lacking a distinct medulla and cortex 27. Birds lacking the large follicles were unable to mount an active antibody response, and it is possible that these histological changes contribute to immunosuppression (see below).

Clinical signs

The outcome of infection can be influenced by many variables, for example, the breed of bird, the age at the time of infection, pre-existing immunity or maternal antibody titres, the strain of virus, the dose of inoculum, the route of inoculation and other stress factors, co-morbidities, or co-infections. The period of greatest susceptibility to clinical signs is 3-6 weeks of age. Birds infected at earlier ages typically show fewer clinical signs, but continue to have evidence of immunosuppression. Following a 1 to 3 day incubation period, signs and symptoms rapidly progress following infection and typically include: ruffled feathers, depression, anorexia, diarrhoea and soiled vent feathers; classical strains of virus cause can cause 10-50% mortality rates in infected flocks, whereas vv IBDV strains can cause 50-100% mortality 7.


The humoral response to vaccines has been shown to be suppressed following IBDV infection 28, and chickens that have a history of IBDV infection are more susceptible to a variety of diseases including: inclusion body hepatitis, coccidiosis, Marek’s disease, haemorrhagic-aplastic anaemia, gangrenous dermatitis, infectious laryngotracheitis, infectious bronchitis, chicken infectious anaemia, salmonellosis, colibacillosis, campylobacter 7 and avian influenza 29. Intriguingly, although the humoral response to secondary infections is impaired, the response to IBDV itself can be unaffected 30 for reasons that remain unknown. In addition, IBDV infection can also suppress cell-mediated immunity 7. Therefore, the effect of IBDV infection on the immune system is complex and our understanding is incomplete. Immunosuppression is economically important due to an increase in susceptibility to secondary infection and a poor responsiveness to vaccination programmes. Moreover, as some secondary infections, such as E. coli, campylobacter, salmonella and avian influenza, are potential public health concerns, understanding IBDV-induced immunosuppression is a priority.


The virus is enzootic worldwide. Two serotypes are recognised, designated Serotype 1 and 2, which share only 30% antigenic relatedness; immunisation against serotype 2 does not protect against serotype 1. Antibodies to both serotypes are common in chickens. Serotype 2 does not cause clinical signs of disease in chickens, unlike serotype 1. Within Serotype 1, classical, variant and very virulent viruses have been described 7. Reassortment is known to occur between serotype 1 viruses, and also between viruses in serotypes 1 and 2 31,32.

Chickens and turkeys are the natural hosts, although IBDV has been isolated from waterfowl, penguins, an ostrich, and a magpie. IBDV RNA has also been detected in naturally infected pigeons and guinea fowl, and in quail that were experimentally inoculated. In addition, antibodies to IBDV have been detected in rooks, pheasants, penguins, ducks, gulls, shearwaters, crows, and falcons 7. IBDV has also been isolated from the lesser mealworm and mosquitos found in an area where chickens were being raised. Moreover, antibodies against IBDV have been found in rats found dead on poultry farms with a history of IBDV, and a dog fed infected chickens shed IBDV in its faeces following ingestion 7.


Strict hygiene management is essential. The virus is hardy in the environment and can persist in poultry houses for up to 122 days, even following thorough cleaning and disinfection 7. Along with good management practices, vaccination is key to controlling the disease. The main correlate of protection is high serum neutralising antibody titres, and inactivated and live attenuated vaccines have been licenced for decades. As young birds can become infected, it is essential to provide protection early in life, and typically layer birds are vaccinated in order to provide maternal antibodies to protect the newly hatched chicks. A prime-boost strategy with a live vaccine prime and inactivated boost has been shown to be successful in providing good maternal antibody titres in newly hatched chicks (reviewed by Muller et al. 33).

Live attenuated vaccines are convenient for vaccinating large numbers of broilers as they can be added to drinking water 1. Moreover, inactivated vaccines require the use of an adjuvant in order to be efficacious, and multiple doses may be necessary, increasing the cost. However, maternal antibodies can neutralise vaccine viruses and impair their efficacy. It is therefore necessary to wait until maternal antibody titres have waned over the fist few weeks of life before vaccinating broilers with live vaccines. However, as maternal antibody titres wane, there is an increased risk the chicks may first become infected with wild-type (wt) IBDV. Therefore the optimal timing for vaccination is difficult to predict 33.

Newer vaccines have been developed that can be given in ovo or to day old chicks, even in the presence of maternally derived antibodies, with the aim of protecting birds once maternal antibodies have waned, thus eliminating the risk of disease due to a wt infection. One example is an immune complex vaccine generated by mixing an IBDV vaccine strain with serum from hyperimmunized birds 1. While the mechanism of action is poorly understood, antibody complexing was found to delay the detection of virus in tissues 34. Another example is the use of recombinant vectors such as herpes virus of turkeys (HVT) to deliver the IBDV VP2 gene. Vectored vaccines have been licenced, and billions of doses have been used worldwide 1.

Concluding remarks

Despite being identified more than 50 years ago and the widespread use of vaccines, IBDV strains continue to circulate globally. Moreover, strains that are either antigenically variant or very virulent have emerged and spread. The infection continues to be costly to the poultry industry worldwide, through both the morbidity/mortality associated with the infection and due to secondary effects due to immunosuppression, which can reduce the effectiveness of vaccines and increase the susceptibility of birds to secondary infections, including potential zoonoses. Therefore, in order to adequately control infectious diseases of poultry, maintain a healthy poultry industry that can secure sufficient food for the growing population, and help reduce the likelihood of zoonotic infections of people, it is essential to control morbidity, mortality and immunosuppression caused by IBDV.

Contributed by:

Andrew Broadbent (The Pirbright Institute)

Copyright © 2016 Andrew Broadbent

First posted: 16-Nov-2016


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