Abstract

Porcine reproductive and respiratory syndrome virus (PRRSV) continues to cause severe reproductive and respiratory pathologies resulting in immense monetary and welfare costs for the swine industry. The vaccines against PRRSV are available; but they struggle with providing protection against the plethora of heterologous PRRSV strains. To improve PRRSV vaccine development, the aim of this study was to provide an in-depth analysis of the crucial heterologous T-cell response to type-2 PRRSV. Following PRRSV modified live virus (MLV) vaccination or infection using one high- or one low-pathogenic PRRSV-strain, this nine-week study evaluated the T-cell response to different PRRSV strains. Our results demonstrate an important role for T cells in this homo- and heterologous response. Specifically, the T-helper cells were the main responders during viremia. Their peak response at 28 dpi correlated with a reduction in viremia, and their homing receptor expression indicated the additional importance for the anti-PRRSV response in the lymphatic and lung tissue. The cytotoxic T lymphocyte (CTL) response was the strongest at the site of infection—the lung and bronchoalveolar lavage. The TCR-γδ T cells were the main responders post viremia and PRRSV induced their expression of the lymph node homing the chemokine receptor, CCR7: This indicates a crucial role for TCR-γδ T cells in the anti-PRRSV response in the lymphatic system.

Highlights

  • Porcine reproductive and respiratory syndrome virus Type 2 (PRRSV-2) causes severe reproductive and respiratory pathology leading to tremendous financial losses for the swine industry

  • This paper addresses four specific gaps identified by Loving et al and Lunney et al.: (1) To develop a methodology to investigate the antigen-specific expansion of the T-cell subsets and the establishment of memory cell populations [1]; (2) to develop a system to evaluate the PRRSV-2 vaccine induced cross-protection to the heterologous virus strain [2]; (3) to investigate the time course of Treg induction during infection [1]; and (4) the characterization of IFN-γ producing

  • Peripheral blood lymphocyte (PBL) counts are depicted in Figure 1C: PBLs increased significantly beginning at 21 dpi in LP pigs; both infected groups were significantly higher than MOCK animals at 28 dpi

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Summary

Introduction

Porcine reproductive and respiratory syndrome virus Type 2 (PRRSV-2) causes severe reproductive and respiratory pathology leading to tremendous financial losses for the swine industry. For the host, an effective T-cell response to PRRSV-2 would display the characteristics of a strong T-helper type 1 (Th1) response: Early CD4+ Th proliferation and significant production of IFN-γ; the differentiation of PRRSV-reactive Th cells into both, lymph node homing central memory (TCM ) and tissue homing effector memory (TEM ) populations [14]; and the induction of multifunctional memory T cells (Tmulti ). These Tmulti combine the best characteristics of memory cells: Tmulti have a long lifespan; they produce high levels of cytokines, such as IFN-γ, IL-2, and TNF-α; they can home to the lymph nodes and tissue; they have been identified as the best correlates of Viruses 2019, 11, 796; doi:10.3390/v11090796 www.mdpi.com/journal/viruses

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