Porcine Reproductive and Respiratory Syndrome Virus Persistence in Blood, Spleen, Lymph Nodes, and Tonsils of Experimentally Infected Pigs Depends on the Level of CD8^highT Cells

Abstract

Porcine reproductive and respiratory syndrome virus (PRRSV) induces a persistent viral infection suggesting an inefficient cellular immune response. The aim of the study was to evaluate the relationship between viral persistence and cytotoxic cells in blood, spleen, mediastinal lymph nodes (MLN) and tonsils of PRRSV experimentally infected pigs. Groups of four to six specific pathogen-free (SPF) pigs were infected with the LHVA-93-3 isolate, and blood and lymphoid organs were collected from 3 to 60 days post-infection (p.i.). Infectious particles and viral RNA were more or less rapidly eliminated in serum, spleen, lungs and MLN but persisted the longest in tonsils. Lymphocytes CD2+ CD4+, CD2+ CD8high, CD2+ CD8low and NK cells populations were phenotyped and their reactivity to PHA and ConA were tested. Analysis of T cell subsets in blood and lymphoid organs indicated that the percentages of CD2+ CD8+ T cells slightly increased in spleen at 17 days p.i, whereas no changes were observed in CD2+ CD4+ cells in blood or lymphoid organs. However, discrimination of CD8+ cells in CD8high and CD8low subsets revealed that the percentages of CD2+ CD8high cells increased in spleen and blood from 10 to 45 or 60 days p.i. while they transiently increased in MLN and decreased in tonsils. The CD8low/CD8high ratio increased in the blood of PRRSV-infected animals at three days p.i. due to a transient decrease of CD2+ CD8high cells. This same ratio decreased in the spleen of infected pigs from 10 to 45 days p.i. due to an increase of CD2+ CD8high cells. The CD2+ MIL-4+ cell subset (NK cells) was not significantly modified in blood or lymphoid organs. In addition, the ability of lymphoid T cells from blood and lymphoid organs to respond to ConA or PHA stimulation was transiently impaired in blood and spleen during the PRRSV persistent infection. Taken together, these results suggest that, in persistently infected pigs, an impaired CD2+ CD8high cell response in MLN and tonsils favors viral persistence in these organs, in contrast with the response seen in blood and spleen where viral elimination appears to occur sooner.

Differences in Clinical Disease and Immune Response of Pigs Challenged with a High-Dose versus Low-Dose Inoculum of Porcine Reproductive and Respiratory Syndrome Virus

“…Again, neither sera vRNA load nor antibody levels were different between days 2 and 12 PI, but sera vRNA loads were quite different on day 1 and day 19 PI. It has been shown that PRRSV persists mainly in lymph nodes and tonsils, but is cleared from the blood (23,43,44). Lavage fluid and TBLN cell virus isolation results were similar between the low-dose and high-dose groups on days 3 and 5 PI (three of three pigs were positive); however, we did not quantify tissue viral load at any time point.…”

Functional impairment of PRRSV-specific peripheral CD3+CD8highcells

“…[28] reported an increased number of CD8 + T-lymphocytes in periarteriolar lymphoid sheets of the spleen and in the paracortex of superficial inguinal lymph nodes of PRRSV-infected pigs, starting from 10 dpi. Other studies describe an influx of CD8 + T-lymphocytes in the blood, lungs and medial retropharyngeal lymph nodes of infected pigs, starting from 10 to 24 dpi [3, 33, 49, 50]. This suggests that PRRSV-specific CD8 + T-lymphocytes migrate from lymphoid sites of initial activation to sites of antigen deposition.…”

Review on the transmission porcine reproductive and respiratory syndrome virus between pigs and farms and impact on vaccination

“…The lungs and the lymphoid organs such as tonsils, Peyer’s patches, thymus, and spleen [15, 28–30] are the tissues with the highest viral loads in the initial phase. In lungs the virus is usually detected from 1 day post-exposure until 28 dpi [30, 31], although persistence of virus in the lungs been described until 49 days post-exposure in young pigs [32].…”