Abstract

Newcastle disease (ND), caused by infections with virulent strains of Newcastle disease virus (NDV), is one of the most important infectious disease affecting wild, peridomestic, and domestic birds worldwide. Vaccines constructed from live, low-virulence (lentogenic) viruses are the most accepted prevention and control strategies for combating ND in poultry across the globe. Avian macrophages are one of the first cell lines of defense against microbial infection, responding to signals in the microenvironment. Although macrophages are considered to be one of the main target cells for NDV infection in vivo, very little is known about the ability of NDV to infect chicken macrophages, and virulence mechanisms of NDV as well as the polarized activation patterns of macrophages and correlation with viral infection and replication. In the present study, a cell culture model (chicken bone marrow macrophage cell line HD11) and three different virulence and genotypes of NDV (including class II virulent NA-1, class II lentogenic LaSota, and class I lentogenic F55) were used to solve the above underlying questions. Our data indicated that all three NDV strains had similar replication rates during the early stages of infection. Virulent NDV titers were shown to increase compared to the other lentogenic strains, and this growth was associated with a strong upregulation of both pro-inflammatory M1-like markers/cytokines and anti-inflammatory M2-like markers/cytokines in chicken macrophages. Virulent NDV was found to block toll-like receptor (TLR) 7 expression, inducing higher expression of type I interferons in chicken macrophages at the late stage of viral infection. Only virulent NDV replication can be inhibited by pretreatment with TLR7 ligand. Overall, this study demonstrated that virulent NDV activates a M1-/M2-like mixed polarized activation of chicken macrophages by inhibition of TLR7, resulting in enhanced replication compared to lentogenic viruses.

Highlights

  • Newcastle disease (ND), caused by the virulent Newcastle disease virus (NDV), is a highly contagious and fatal viral infectious ­disease in birds and can have devastating economic effects on global domestic poultry production

  • While no differences in replication kinetics were observed between the two lentogenic NDV strains from 24 to 72 hpi, NDV strain LaSota presented a reduced ability to replicate in chicken macrophages (HD11) at 4 and 12 hpi, as evidenced by lower viral genomic RNA loads, when compared with the lentogenic NDV strain F55 (Figure 2A)

  • These results indicate that virulent NDV replicates more rapidly than lentogenic viruses in chicken macrophages in vitro

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Summary

Introduction

Newcastle disease (ND), caused by the virulent Newcastle disease virus (NDV), is a highly contagious and fatal viral infectious ­disease in birds and can have devastating economic effects on global domestic poultry production. ND is listed by the World Health Organization for Animals (OIE) as a vitally important pathogen for avian species and products, in which NDV detection in a specific geographical location often leads to trade restrictions and embargoes [1]. NDV was previously synonymous with avian paramyxovirus type 1 [2]; due to changes in taxonomy is referred to as avian avulavirus [3]. NDV is an enveloped virus containing a single-stranded, negative-sense, non-segmented RNA genome that is approximately 15,000 nucleotides in length. Strains of NDV are grouped into virulent (velogenic), intermediate (mesogenic), and non-virulent or low virulent (lentogenic) on the basis of the clinical signs seen in infected chickens [2]

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