Cellular pathogenesis of porcine circovirus type 2 infection

Dvorak, Cheryl M.T.; Puvanendiran, S.; Murtaugh, Michael P.

doi:10.1016/j.virusres.2013.03.001

Cited by 25 publications

(20 citation statements)

References 35 publications

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“…It is noteworthy that the absence of significant differences or erratic responses during the early time points after vaccination could have been influenced by the ability of the whole virus used as in vitro recall antigen to induce inhibition of immune responsiveness that counteracted cell activation [8,33,48]. …”

Section: Discussionmentioning

confidence: 99%

Memory T cell proliferative responses and IFN-γ productivity sustain long-lasting efficacy of a Cap-based PCV2 vaccine upon PCV2 natural infection and associated disease

Ferrari

Borghetti

Angelis

et al. 2014

Vet Res

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Porcine circovirus type 2 (PCV2) vaccination represents an important measure to cope with PCV2 infection; however, data regarding the modulation of the immune cell compartment are still limited, especially under field conditions. This study is aimed at investigating the features of the cellular immune response in conventional piglets induced by vaccination using a capsid (Cap) protein-based PCV2 vaccine compared to unvaccinated animals when exposed to PCV2 natural infection. Immune reactivity was evaluated by quantifying peripheral cell subsets involved in the anti-viral response and characterizing the interferon-gamma (IFN-γ) secreting cell (SC) responsiveness both in vivo and upon in vitro whole PCV2 recall. The vaccination triggered an early and intense IFN-γ secreting cell response and induced the activation of peripheral lymphocytes. The early increase of IFN-γ SC frequencies resulted in a remarkable and transient tendency to increased IFN-γ productivity in vaccinated pigs. In vaccinated animals, soon before the onset of infection occurred 15-16 weeks post-vaccination, the recalled PCV2-specific immune response was characterized by moderate PCV2-specific IFN-γ secreting cell frequencies and augmented productivity together with reactive CD4+CD8+ memory T cells. Conversely, upon infection, unvaccinated animals showed very high frequencies of IFN-γ secreting cells and a tendency to lower productivity, which paralleled with effector CD4–CD8+ cytotoxic cell responsiveness. The study shows that PCV2 vaccination induces a long-lasting immunity sustained by memory T cells and IFN-γ secreting cells that potentially played a role in preventing the onset of infection; the extent and duration of this reactivity can be an important feature for evaluating the protective immunity induced by vaccination.

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Section: Discussionmentioning

confidence: 99%

Memory T cell proliferative responses and IFN-γ productivity sustain long-lasting efficacy of a Cap-based PCV2 vaccine upon PCV2 natural infection and associated disease

Ferrari

Borghetti

Angelis

et al. 2014

Vet Res

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“…However, the fact that severe inflammation occurs during the early stage of PCV2 infection is key in the development of more-severe clinical symptoms, because if initial inflammation is not alleviated, it often leads to chronic inflammatory responses that deplete immune cells within the secondary lymphoid tissues of infected pigs (Darwich et al, 2003;Dvorak et al, 2013). We propose a novel role of PCV2 ORF2 in manipulating host immune responses.…”

Section: Dapimentioning

confidence: 86%

ORF2 protein of porcine circovirus type 2 promotes phagocytic activity of porcine macrophages by inhibiting proteasomal degradation of complement component 1, q subcomponent binding protein (C1QBP) through physical interaction

Choi

Lee

et al. 2015

Journal of General Virology

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Defining how each ORF of porcine circovirus type 2 (PCV2) manipulates the host immune system may be helpful to understand the disease progression of post-weaning multisystemic wasting syndrome. In this study, we demonstrated a direct interaction between the PCV2 ORF2 and complement component 1, q subcomponent binding protein (C1QBP) within the cytoplasm of host macrophages. The physical interaction between PCV2 ORF2 and C1QBP inhibited ubiquitin-mediated proteasomal degradation of C1QBP in macrophages. Increased stability of C1QBP by the interaction with PCV2 ORF2 further enhanced the phagocytic activity of porcine macrophages through the phosphoinositol 3-kinase signalling pathway. This may explain the molecular basis of how PCV2 ORF2 enhances the phagocytic activity of host macrophages.

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“…During the early stages of PCV2 infection, innate immune cells secrete excessive amounts of proinflammatory cytokines, which often leads to a chronic inflammatory response (Darwich et al, 2003). Then, the chronic inflammatory response substantially depletes immune cells by apoptosis within lymphoid tissues (Dvorak et al, 2013). Therefore, defining the mechanism of why severe inflammation occurs during the early stage of PCV2 infection is the key to developing a method to prevent the initiation of porcine circovirus-associated diseases.…”

Section: Discussionmentioning

confidence: 99%

The ORF3 protein of porcine circovirus type 2 promotes secretion of IL-6 and IL-8 in porcine epithelial cells by facilitating proteasomal degradation of regulator of G protein signalling 16 through physical interaction

Choi

Rho

Kim

et al. 2015

Journal of General Virology

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Porcine circovirus type 2 (PCV2) is the main aetiological agent of postweaning multisystemic wasting syndrome. The mechanism of pathogenicity associated with PCV2 infection is still not fully understood. Nevertheless, the fact that large amounts of proinflammatory cytokines within lymphoid tissues are released during the early stage of PCV2 infection may induce chronic inflammatory responses followed by the destruction of lymphoid tissues. However, how PCV2 infection causes an excessive inflammatory response in the host immune system during the early stage of PCV2 infection has still not been elucidated. In this study, we show that direct interaction between the PCV2 ORF3 and regulator of G protein signalling 16 (RGS16) within the cytoplasm of host cells leads to ubiquitin-mediated proteasomal degradation of RGS16. Facilitated degradation of the RGS16 by PCV2 ORF3 further enhances NFkB translocation into the nucleus through the ERK1/2 signalling pathway and increased IL-6 and IL-8 mRNA transcripts. Consequently, more severe inflammatory responses and leukocyte infiltration occur around host cells. This evidence may be the first clue explaining the molecular basis of how excessive amounts of proinflammatory cytokines within lymphoid tissues are released during the early stage of PCV2 infection.

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Cellular pathogenesis of porcine circovirus type 2 infection

Cited by 25 publications

References 35 publications

Memory T cell proliferative responses and IFN-γ productivity sustain long-lasting efficacy of a Cap-based PCV2 vaccine upon PCV2 natural infection and associated disease

Memory T cell proliferative responses and IFN-γ productivity sustain long-lasting efficacy of a Cap-based PCV2 vaccine upon PCV2 natural infection and associated disease

ORF2 protein of porcine circovirus type 2 promotes phagocytic activity of porcine macrophages by inhibiting proteasomal degradation of complement component 1, q subcomponent binding protein (C1QBP) through physical interaction

The ORF3 protein of porcine circovirus type 2 promotes secretion of IL-6 and IL-8 in porcine epithelial cells by facilitating proteasomal degradation of regulator of G protein signalling 16 through physical interaction

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