Identification of a sequence from the genome of porcine circovirus type 2 with an inhibitory effect on IFN-α production by porcine PBMCs

Abstract

Porcine circovirus type 2 (PCV-2) has been identified as the causal agent of postweaning multisystemic wasting syndrome and has been associated with several other disease syndromes in pigs. To date, however, little is known regarding the mechanism(s) underlying the pathogenesis of PCV-2-induced diseases and the interaction of the virus with the host immune system. In the present study, oligodeoxynucleotides (ODNs), with central CpG motifs selected from the genome of PCV-2, were demonstrated to modulate the immune response of porcine PBMCs. Four of the five ODNs tested were demonstrated to act in a stimulatory manner via induction of IFN-a production, whereas only one of the five ODNs showed inhibitory activity. Also, this inhibitory ODN was demonstrated to completely inhibit IFN-a production induced by the other stimulatory ODNs and showed a variable degree of inhibitory action on other known inducers of IFN-a. Although no single common characteristic among resistant or susceptible inducers could be identified, the presence of immune modulatory sequences in the genome of PCV-2 may represent an underlying mechanism of the pathogenesis of PCV-2-associated diseases.

Protective immunity against porcine circovirus 2 by vaccination with ORF2-based DNA and subunit vaccines in mice

“…Unmethylated CpG motifs in the plasmid are one of the pathogen-associated molecular patterns that tend to drive Th1 immune responses via Toll-like receptor 9 (Hemmi et al, 2000). Presently, at least one CpG-containing sequence has been identified as a potent inducer of IFN-a production in PCV2 ORF2 (Hasslung et al, 2003). In contrast, Th2 cells, which predominantly produce IL-4, IL-5, IL-10 and IL-13, promote the development of eosinophilia as well as the generation of IgG1 and IgE antibody isotypes (Abbas et al, 1996;Mosmann & Coffman, 1989a).…”

Structure-Dependent Modulation of Alpha Interferon Production by Porcine Circovirus 2 Oligodeoxyribonucleotide and CpG DNAs in Porcine Peripheral Blood Mononuclear Cells

“…One of these ODNs (ODN PCV2/5) was selected based on the presence of the hexamer TTCGAA that is also present in the reference phosphodiester ODN H (33,42). ODN PCV2/5 induced high levels of IFN-␣, whereas another ODN from the PCV2 genome (PCV2/1) strongly inhibited the IFN-␣ production (19).…”

“…It has been postulated that PCV2 elicits immunomodulatory effects through the presence of both immune stimulatory and inhibitory DNA sequences within the viral genome (19). Bacterial and viral DNA containing unmethylated CpG motifs can act as danger signals in vertebrates, activating innate immunity through Toll-like receptor 9 (TLR9) (39).…”

“…1010 Stoon) genome were characterized with regard to their IFN-␣ modulatory capacity in porcine PBMCs (poPBMCs) (19). One of these ODNs (ODN PCV2/5) was selected based on the presence of the hexamer TTCGAA that is also present in the reference phosphodiester ODN H (33,42).…”

Development and evaluation of a recombinant DNA vaccine candidate expressing porcine circovirus 2 structural protein

“…Clinical signs include progressive dyspnea, weight loss, jaundice, emaciation, and respiratory and digestive disorders (Harding & Clark 1997, Lecann et al 1997, Nayar et al 1997. PCV2 associated ailments are considered important swine diseases and have potentially serious economic impact on the swine industry worldwide , Rodriguez-Arrioja et al 2002, Hasslung et al 2003. PCV2 viral particles are very stable and are able to persist in the environment of infected herds, making virus eradication very difficult (Cho et al 2006).…”