Transcriptomic analysis of the Chicken Anaemia Virus (CAV)-induced immunosuppression

Chicken anaemia virus (CAV) is an unusually small virus that causes severe anaemia and immunosuppression in young chickens. Such effects reduce the efficiency of routine vaccinations while aggravating the effects of other pathogens in chicken populations, constituting a serious economic threat to poultry industry. The replication/pathogenicity of CAV relies on the expression of only a single structural protein VP1 and two non-structural proteins VP2 and VP3 (apoptin). The function of each individual protein is as yet unclear. This study has used transcriptional profiling to identify pathways that are dramatically modulated after 48 hr of infection in an in vitro model (MDCC-MSB1 cells) and after 4 days of experimental infection (1-day-old chickens in vivo model), using Affymetrix chicken oligonucleotide arrays. Changes in transcript levels between infected and uninfected cells indicate a dysfunction in the Mitogen Activated Protein kinases (MAPK) and T cell receptor signalling cascades implying that CAV might subvert host signalling responses to its own benefit. Two highly passaged attenuated cloned isolates and three VP3 CAV mutant viruses were also used in this study with the aim of elucidating the interactions of each of these proteins with the host cell. VP3 mutations resulted in lower levels of transcripts encoding signalling, transcription and mitosis related proteins. Overall, these data extend our understanding of how broadly CAV alters the regulation of host gene products and highlight the virus' 'need' to utilise the host cell machinery to replicate itself.