Pigs that recover from porcine reproduction and respiratory syndrome virus infection develop cytotoxic CD4+CD8+ and CD4+CD8- T-cells that kill virus infected cells

Abstract

Porcine reproductive and respiratory syndrome virus (PRRSV) infection is difficult to control because the virus undergoes antigenic variation during infection and also modulates the protective host immune response. Although current vaccines do not provide full protection, they have provided insight into the mechanisms of protection. Live PRRSV vaccines induce partial protection before the appearance of neutralizing antibody, suggesting cell-mediated immunity or other mechanisms may be involved. Herein, we demonstrate recovery from infection is associated with development of cytotoxic T-lymphocytes (CTL) that can kill PRRSV-infected target cells. Initial experiments showed survival of PRRSV-infected monocyte derived macrophage (MDM) targets is reduced when overlaid with peripheral blood mononuclear cells (PBMC) from gilts that had recovered from PRRSV infection. Further studies with PBMC depleted of either CD4+ or CD8+ T-cells and positively selected subpopulations of CD4+ and CD8+ T-cells showed that both CD4+ and CD8+ T-cells were involved in killing. Examination of killing at different time points revealed killing was biphasic and mediated by CTL of different phenotypes. CD4+CD8+high were associated with killing target cells infected for 3–6 hours. CD4+CD8- CTL were associated with killing at 16–24 hours. Thus, all the anti-PRRSV CTL activity in pigs was attributed to two phenotypes of CD4+ cells which is different from the anti-viral CD4-CD8+ CTL phenotype found in most other animals. These findings will be useful for evaluating CTL responses induced by current and future vaccines, guiding to a novel direction for future vaccine development.

Dynamics and Differences in Systemic and Local Immune Responses After Vaccination With Inactivated and Live Commercial Vaccines and Subsequent Subclinical Infection With PRRS Virus

“…Despite the fact that many studies focused on PRRS immunoprophylaxis have already been published and many procedures are implemented in the agricultural industry, a universal model does not yet exist (46)(47)(48)(49)(50)(51)(52)(53)(54)(55)(56)(57)(58)(59)(60). The use of live attenuated vaccines is generally preferred as was also confirmed in our field study (61).…”

“…The CD4 − CD8 + subpopulation belongs to cytotoxic groups of cells, CD4 + CD8 + is considered a group of Th1 memory cells (51). In another study the expression of cytotoxic CD4 + CD8 + and CD4 + CD8 − was described which help to recover from PRRS infection (52).…”

Bovine Herpesvirus-4-Vectored Delivery of Nipah Virus Glycoproteins Enhances T Cell Immunogenicity in Pigs

“…These data support the further evaluation of these vectors for efficacy against NiV and potentially further development as DIVA vaccines which could be prophylactically or reactively to prevent/control NiV outbreaks. The prodigious T cell responses demonstrated with the BoHV-4 vectors also supports their evaluation in the delivery of antigens from other porcine viruses for which T cells are thought to play an important role in protection of, e.g., African swine fever [85,86] and porcine reproductive and respiratory syndrome viruses [87,88].…”

Genetic diversity and different cross-neutralization capability of porcine circovirus type 2 isolates recently circulating in South Korea

“…PCV2-positive clinical tissue extracts were infected with PK15 cells, which were all types of PCV-free as con rmed by PCR, and PCV2 isolates including PCV2a, 2b, and 2d genotypes were propagated with high titer (10 5 -10 6 TCID 50 /mL). Viral titration was conducted following the previous report [25] and viral titers were determined by immunostaining using PCV2-speci c monoclonal antibodies (mAbs). Based on the amino acid sequence of ORF2 and growth e ciency in PK15 cells, representative isolates of two PCV2d (QIA169 and QIA244) were selected for evaluation of cross-reactivity along with PCV2a (QIA215) and PCV2b (QIA418) genotypes.…”