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 f r o m i n fected c h i c k e n s . 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)-g production in the latter. CD4 þ and CD8 þ 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 i n t r a t r a c h e a l 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 Viral Interleukin-8 Promotes Lymphoma Formation through Targeted Recruitment of B Cells and CD4 + CD25 + T Cells

“…Thus, it is tempting to speculate that the vIL-8 chemokine might recruit B cells to the initial site of infection in the lung. Furthermore, the well-known delay in disease progression in the absence of B cells, e.g., upon bursectomy, underscores that B cells play a central role during early infection (3,33). The lack of B-cell recruitment in v⌬MetvIL-8-infected chickens could explain the reduced viral load in chickens infected via the natural route.…”

“…In the respiratory tract, virus is likely taken up by macrophages and/or dendritic cells that transport the virus to the primary lymphoid organs; however, infected B cells can be detected in the lung as early as 2 days postinfection (3). Upon transport to the primary lymphoid organs, MDV efficiently replicates in B cells and subsequently infects activated CD4 ϩ T cells that carry the virus to the feather follicle epithelium, where infectious virus is produced and shed into the environment.…”

Replication ability of three highly protective Marek's disease vaccines: implications in lymphoid organ atrophy and protection

“…The RM1 strain replicated extensively in the lung and infected the cells lining the parabronchi and within the pulmonary interstitium. The pattern of expression of pp38 in the lung of chickens inoculated with RM1 resembled those after infection with oncogenic strains (Purchase, 1970;Adldinger & Calnek, 1973;St Hill et al, 2004;Baaten et al, 2009). Purchase (1970) detected MDV antigens in epithelial cells lining the air capillaries of lungs 5 days after intra-abdominal inoculation with various oncogenic MDV strains.…”

“…St Hill et al (2004) detected the DNA of an oncogenic MDV in lungs of chickens following 3, 5, 7, and 10 d.p.i. Baaten et al ( 2009) demonstrated infection of macrophages and B cells in the lung of chickens infected intratracheally with oncogenic MDV. The nature of cells supporting infection with oncogenic and attenuated serotype 1 MDV is still unknown, and further studies using double-staining techniques like immunofluorescence/immunohistochemistry or in situ hybridization will be needed.…”

A B-cell targeting virus disrupts potentially protective genomic methylation patterns in lymphoid tissue by increasing global 5-hydroxmethylcytosine levels

“…It was in chickens that the existence of the bursa of Fabricius (BF) and the B-cells that specialise in antibody production within it was first described [21]. Avian B-cells are crucial for inducing antibody responses against viral pathogens; in response viruses that infect birds often target B-cells to avoid elimination [22,23]. One such pathogen of veterinary and economic significance is infectious bursal disease virus (IBDV) which infects and subsequently causes cell death of developing B-cells as part of a mechanism to avoid elimination from the host [23][24][25].…”