The Level of Virus-Specific T-Cell and Macrophage Recruitment in Porcine Reproductive and Respiratory Syndrome Virus Infection in Pigs Is Independent of Virus Load

Abstract

Porcine reproductive and respiratory syndrome virus (PRRSV) is the most important infectious disease agent of pigs worldwide, causing reproductive failure in pregnant sows and respiratory problems in nursing and growing pigs. PRRSV infection is characterized by a prolonged viremia of 30 or more days and an extended persistent infection of lymphoid tissues. To better understand the immunological basis for prolonged acute and persistent PRRSV infection, we have examined the cell-mediated immune (CMI) response throughout the course of infection and compared the results to the local distribution and abundance of PRRSV in infected tissues. PRRSV-specific T cells, enumerated by gamma interferon enzyme-linked immunospot assay, did not appear until 2 weeks after PRRSV inoculation, and their abundance exhibited substantial variation over time and among animals. In all cases the T-cell response was transient. High levels of viral RNA were present in lymphoid tissues of all animals in the acute phase of infection. Viral loads were decreased 1,000-fold or more in persistent infections, with the primary sites of persistence being tonsil, sternal lymph node, and inguinal lymph node. The abundance of virus-specific T cells in either acutely or persistently infected animals was highly variable and showed no correlation to the level of virus in lymphoid tissues. No significant difference in antigen-specific T-cell abundance was observed in secondary lymphoid tissues in either acute or persistent infection except for tonsil, in which the number of responding cells was extremely low. CD4؉ -and CD8 ؉ -T-cell frequencies did not change after PRRSV infection, though a decrease in ␥␦ T cells was observed. Macrophages, the permissive cell type for PRRSV, were present in various levels in all tissue preparations and were not in proportion to local virus load. These findings indicate that a weak CMI response contributes to prolonged PRRSV infection and suggests that PRRSV suppresses T-cell recognition of infected macrophages. Thus, the slow but eventual resolution of PRRSV infection may be dependent on limiting permissive macrophages and on innate immune factors.

Antibody Repertoire Development in Fetal and Neonatal Piglets: XIX. Undiversified B Cells with Hydrophobic HCDR3s Preferentially Proliferate in the Porcine Reproductive and Respiratory Syndrome

“…18). PRRSV Ags are localized primarily in porcine alveolar macrophages in infected piglets (19,20), suggesting that PRRSV replicates in vivo in porcine alveolar macrophages and in other macrophages and dendritic cells throughout the body (21,22). On average, 40 -80% of herds are infected by PRRSV in the United States and Europe (18,23).…”

The role of mathematical models of host–pathogen interactions for livestock health and production – a review

“…The characteristic of most interest to the first question above is that a decline in virus load to low levels as shown in Figure 5a and observed in empirical studies is only possible if the total number of macrophages decreases substantially. This, however, contradicts empirical findings, which suggest that macrophage numbers in infected tissues remain constant during the time course of infection (Labarque et al, 2003;Xiao et al, 2004). Applying the additional constraint that macrophages are replenished at a rate corresponding to a constant number of macrophages leads to a new persistent equilibrium.…”

Regulatory T Cells and Viral Disease

“…The initial IFN- response is not PRRSV-specific and may be a result of activation of natural killer cells (Wesley RD, 2006). A PRRSV-specific T lymphocyte IFN- response does not appear until at least 2 weeks after infection (Xiao Z, 2004). The IFN- response gradually increases and plateaus at 6 months postinfection, and is associated with a slow increase in neutralizing antibody (Lopez OJ, 2004;Meier WA, 2003).…”

“…Since the initial description of porcine reproductive and respiratory syndrome (PRRS) in the USA in 1987 (Collins JE, 1992;Keffaber, 1989), the disease has been shown to be endemic in many swine producing countries, and is now considered to be the most important disease of swine worldwide (www.prrs.org, (Xiao Z, 2004)). In the USA alone, economic losses caused by PRRS virus (PRRSV) infection are estimated to total $560 million (www.prrs.org).…”