Nasal mucosal administration of chitin microparticles boosts innate immunity against influenza A virus in the local pulmonary tissue.

Influenza virus infection remains a major health concern due to morbidity and mortality associated with epidemics and occasional pandemics. The absence of acquired immunity to antigenically distinct, emerging virus strains stresses the need for a generic drug that protects independent of vaccination. Here, we demonstrate that prophylactic administration of chitin microparticles (CMP) via the intranasal route significantly reduced lung viral titres and clinical signs. Pre-treatment boosted the innate immune response to subsequent infection by recruiting innate cells, such as neutrophils, and increasing inflammatory cytokines. Although an increase in virus-specific T cells was observed, the memory phase was diminished. Our data demonstrate that in the absence of prior exposure to influenza virus, CMP reduce clinical signs by boosting innate immunity.

Early replication in pulmonary B cells after infection with Marek's disease herpesvirus by the respiratory route.

Abstract Natural infection with Marek's disease virus occurs through the respiratory mucosa after chickens inhale dander shed from infected chickens. The early events in the lung following exposure to the feather and squamous epithelial cell debris containing the viral particles remain unclear. In order to elucidate the virological and immunological consequences of MDV infection for the respiratory tract, chickens were infected by intratracheal administration of infective dander. Differences between susceptible and resistant chickens were immediately apparent, with delayed viral replication and earlier onset of interferon (IFN)-gamma production in the latter. CD4(+) and CD8(+) T cells surrounded infected cells in the lung. Although viral replication was evident in macrophages, pulmonary B cells were the main target cell type in susceptible chickens following intratracheal infection with MDV. In accordance, depletion of B cells curtailed viremia and substantially affected pathogenesis in susceptible chickens. Together the data described here demonstrate the role of pulmonary B cells as the primary and predominant target cells and their importance for MDV pathogenesis.

Marek's disease is a natural model for lymphomas overexpressing Hodgkin's disease antigen (CD30).

Animal models are essential for elucidating the molecular mechanisms of carcinogenesis. Hodgkin's and many diverse non-Hodgkin's lymphomas overexpress the Hodgkin's disease antigen CD30 (CD30(hi)), a tumor necrosis factor receptor II family member. Here we show that chicken Marek's disease (MD) lymphoma cells are also CD30(hi) and are a unique natural model for CD30(hi) lymphoma. Chicken CD30 resembles an ancestral form, and we identify a previously undescribed potential cytoplasmic signaling domain conserved in chicken, human, and mouse CD30. Our phylogeneic analysis defines a relationship between the structures of human and mouse CD30 and confirms that mouse CD30 represents the ancestral mammalian gene structure. CD30 expression by MD virus (MDV)-transformed lymphocytes correlates with expression of the MDV Meq putative oncogene (a c-Jun homologue) in vivo. The chicken CD30 promoter has 15 predicted high-stringency Meq-binding transcription factor recognition motifs, and Meq enhances transcription from the CD30 promoter in vitro. Plasma proteomics identified a soluble form of CD30. CD30 overexpression is evolutionarily conserved and defines one class of neoplastic transformation events, regardless of etiology. We propose that CD30 is a component of a critical intracellular signaling pathway perturbed in neoplastic transformation. Specific anti-CD30 Igs occurred after infection of genetically MD-resistant chickens with oncogenic MDV, suggesting immunity to CD30 could play a role in MD lymphoma regression.

Study of host-pathogen interactions to identify sustainable vaccine strategies to Marek's disease.

Marek's disease virus is a highly cell-associated, lymphotropic alpha-herpesvirus that causes paralysis and neoplastic disease in chickens. The disease has been contained by vaccination with attenuated viruses and provides the first evidence for a malignant cancer being controlled by an antiviral vaccine. Marek's disease pathogenesis is complex, involving cytolytic and latent infection of lymphoid cells and oncogenic transformation of CD4+ T cells in susceptible chickens. Innate and adaptive immune responses develop in response to infection, but infection of lymphocytes results in immunosuppressive effects. The remarkable ability of MDV to escape immune responses by interacting with, and down-regulating, some key aspects of the immune system will be discussed in the context of genetic resistance. Resistance conferred by vaccination and the implications of targeting replicative stages of the virus will also be examined.

Protection from infectious bursal disease virus (IBDV)-induced immunosuppression by immunization with a fowlpox recombinant containing IBDV-VP2.

Immunosuppression resulting from infectious bursal disease virus (IBDV) infection has critical health and welfare implications for birds, yet it is incompletely understood and largely overlooked as a measure of vaccine efficacy. The ability of a fowlpoxvirus recombinant (fpIBD1) containing the VP2 protein of IBDV to protect against IBDV-induced immunosuppression was investigated by measuring the convalescent chicken's ability to mount antibody responses to IBDV infection, and to inactivated IBDV and salmonella vaccines. An immunoglobulin (Ig)M response, but no IgG response, occurred after IBDV infection. Uninfected chickens produced a sustained IgM response and some IgG response to inactivated IBDV vaccine, while in previously infected birds only a transient IgM response was detected. A moderate suppression of the response to a commercial salmonella vaccine was evident after IBDV infection, which was largely prevented by immunization with fpIBD1. These results indicate that measurement of immunosuppression could be a useful strategy for assessing the efficacy of vaccines to protect against the consequences of IBDV infection.