A highly pathogenic porcine reproductive and respiratory syndrome virus type 1 (PRRSV-1) strongly modulates cellular innate and adaptive immune subsets upon experimental infection

Ferrari, Luca; Canelli, Elena; Angelis, Elena De; Catella, Alessia; Ferrarini, Giulia; Ogno, Giulia; Bonati, L.; Nardini, Roberto; Borghetti, Paolo; Martelli, Paolo

doi:10.1016/j.vetmic.2018.02.001

Cited by 24 publications

(18 citation statements)

References 41 publications

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“…There are two main genotypes, Genotype 1 (European type) and Genotype 2 (North American type) [10], with up to 40% difference documented in the whole genome between genotypes, and up to 20% divergence within the same genotype [11]. In addition, the virus is highly immunomodulatory [12,13] which adds another layer of complexity in the efforts to control PRRS.…”

Section: Introductionmentioning

confidence: 99%

A PRRSV GP5-Mosaic vaccine: Protection of pigs from challenge and ex vivo detection of IFNγ responses against several genotype 2 strains

Cui¹,

O’Connell²,

Costa³

et al. 2019

PLoS ONE

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Porcine reproductive and respiratory syndrome virus (PRRSV), is a highly mutable RNA virus that affects swine worldwide and its control is very challenging due to its formidable heterogeneity in the field. In the present study, DNA vaccines constructed with PRRSV GP5-Mosaic sequences were complexed to cationic liposomes and administered to experimental pigs by intradermal and intramuscular injection, followed by three boosters 14, 28 and 42 days later. The GP5-Mosaic vaccine thus formulated was immunogenic and induced protection from challenge in vaccinated pigs comparable to that induced by a wild type (VR2332) GP5 DNA vaccine (GP5-WT). Periodic sampling of blood and testing of vaccine-induced responses followed. Interferon-γ (IFN-γ) mRNA expression by virus-stimulated peripheral blood mononuclear cells (PBMCs) of GP5-Mosaic-vaccinated pigs was significantly higher compared to pigs vaccinated with either GP5-WT or empty vector at 21, 35 and 48 days after vaccination. Cross-reactive cellular responses were also demonstrated in GP5-Mosaic vaccinated pigs after stimulation of PBMCs with divergent strains of PRRSV. Thus, significantly higher levels of IFN-γ mRNA were detected when PBMCs from GP5-Mosaic-vaccinated pigs were stimulated by four Genotype 2 strains (VR2332, NADC9, NADC30 and SDSU73), which have at least 10% difference in GP5 amino acid sequences, while such responses were recorded only upon VR2332 stimulation in GP5-WT-vaccinated pigs. In addition, the levels of virus-specific neutralizing antibodies were higher in GP5-Mosaic or GP5-WT vaccinated pigs than those in vector-control pigs. The experimental pigs vaccinated with either the GP5-Mosaic vaccine or the GP5-WT vaccine were partially protected from challenge with VR2332, as measured by significantly lower viral loads in sera and tissues and lower lung lesion scores than the vector control group. These data demonstrate that the GP5-Mosaic vaccine can induce cross-reactive cellular responses to diverse strains, neutralizing antibodies, and protection in pigs.

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Section: Introductionmentioning

confidence: 99%

A PRRSV GP5-Mosaic vaccine: Protection of pigs from challenge and ex vivo detection of IFNγ responses against several genotype 2 strains

Cui¹,

O’Connell²,

Costa³

et al. 2019

PLoS ONE

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“…It is known that IFN-γ is, mostly produced by activated NK cells, NKT cells, γ/δ T cells, cytotoxic T cells and memory T cells (Gerner et al, 2015;Mair et al, 2014), and participates in regulating the immune and inflammatory responses (Van Reeth and Nauwynck, 2000). In fact, an early increase of NKT cells has been associated with viraemia peak in piglets infected with PR40 virulent strain (Ferrari et al, 2018). In our study, virulent Lena strain elicited a marked increase in the serum level of IFN-γ which was significantly correlated with viremia and lung viral load, suggesting an attempt of the host innate immune response in controlling virus replication.…”

Section: Discussionmentioning

confidence: 99%

“…PRRSV is known to modulate the host immune response by inducing changes in the frequencies of immune cell subsets in blood (Dwivedi et al, 2012;Ferrari et al, 2018;Morgan et al, 2013;Weesendorp et al, 2013) and in tissues (Gómez-Laguna et al, 2010;Rodríguez-Gómez et al, 2013), leading to an enhanced susceptibility to secondary bacterial infections (Karniychuk et al, 2010;Renson et al, 2017;Sinn et al, 2016). An early decrease in the frequency of monocytes, NK cells or cytotoxic T cells linked to a strong inflammatory response in target organs has been described upon experimental infection with PRRSV-1 virulent strains (Ferrari et al, 2018;Morgan et al, 2013;Weesendorp et al, 2013;. In addition, some studies indicate an early overproduction of pro-inflammatory cytokines, such as IFN-γ, IL-1β or IL-8, as the main source of pulmonary injury after infection with virulent PRRSV-1 strains (Amarilla et al, 2015;Morgan et al, 2013;Renson et al, 2017;Weesendorp et al, 2014).…”

Section: Introductionmentioning

confidence: 99%

Activation of pro- and anti-inflammatory responses in lung tissue injury during the acute phase of PRRSV-1 infection with the virulent strain Lena

Sánchez‐Carvajal

Rodríguez-Gómez

Ruedas‐Torres

et al. 2020

Veterinary Microbiology

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Porcine reproductive and respiratory syndrome virus (PRRSV) plays a key role in porcine respiratory disease complex modulating the host immune response and favouring secondary bacterial infections. Pulmonary alveolar macrophages (PAMs) are the main cells supporting PRRSV replication, with CD163 as the essential receptor for viral infection. Although interstitial pneumonia is by far the representative lung lesion, suppurative bronchopneumonia is described for PRRSV virulent strains. This research explores the role of several immune markers potentially involved in the regulation of the inflammatory response and sensitisation of lung to secondary bacterial infections by PRRSV-1 strains of different virulence. Conventional pigs were intranasally inoculated with the virulent subtype 3 Lena strain or the low virulent subtype 1 3249 strain and euthanised at 1, 3, 6 and 8 dpi. Lena-infected pigs exhibited more severe clinical signs, macroscopic lung score and viraemia associated with an increase of IL-6 and IFN-γ in sera compared to 3249-infected pigs. Extensive areas of lung consolidation corresponding with suppurative bronchopneumonia were observed in Lena-infected pigs. Lung viral load and PRRSV-N-protein + cells were always higher in Lena-infected animals. PRRSV-N-protein + cells were linked to a marked drop of CD163 + macrophages. The number of CD14 + and iNOS + cells gradually increased along PRRSV-1 infection, being more evident in Lena-infected pigs. The frequency of CD200R1 + and FoxP3 + cells peaked late in both PRRSV-1 strains, with a strong correlation between CD200R1 + cells and lung injury in Lena-infected pigs. These results highlight the role of molecules involved in the earlier and higher extent of lung lesions in piglets infected with the virulent Lena strain, pointing out the activation of routes potentially involved in the restraint of the local inflammatory response.

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“…The reason for this difference is unclear but may be due to the marked expansion of B cell populations within the SiLN to antigens besides nsp7. As it would not be possible to evaluate all mesenteric lymph nodes or the entire pig spleen, data is presented as nsp7-specific B cells/million B cells for all samples to allow for direct comparison between tissues, corrected for lymphocytosis, and to prevent potential confounding effects of PRRSV on lymphocyte populations (27).…”

Section: Kinetics Of the Nsp7-specific B Cell Response In Immune Tissuesmentioning

confidence: 99%

The PRRSV-Specific Memory B Cell Response Is Long-Lived in Blood and Is Boosted During Live Virus Re-exposure

et al. 2020

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Porcine reproductive and respiratory syndrome virus (PRRSV) is an important pathogen of swine health and well-being worldwide largely due to an insufficient understanding of the adaptive immune response to infection leading to ineffective PRRSV control. The memory and anamnestic response to infection are critical gaps in knowledge in PRRSV immunity. The lack of effective tools for the evaluation of the memory response previously hindered the ability to effectively characterize the porcine memory response to infection. However, the creation and validation of a PRRSV nsp7-specific B cell tetramer now facilitates the ability to detect very rare memory B cells and thus define the memory response of the pig. Here, we describe the PRRSV nsp7-specific B cell response following vaccination and challenge in six key secondary lymphoid organs including the identification of PBMCs as the tissue of interest for the memory immune response in pigs. Following live virus challenge of immune animals, an anamnestic response of nsp7-specific memory B cells and neutralizing antibodies was observed. This characterization of the functional humoral immune response to PRRSV answers key questions involved in regional specialization of the immune response following intramuscular inoculation of PRRSV MLV.

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A highly pathogenic porcine reproductive and respiratory syndrome virus type 1 (PRRSV-1) strongly modulates cellular innate and adaptive immune subsets upon experimental infection

Cited by 24 publications

References 41 publications

A PRRSV GP5-Mosaic vaccine: Protection of pigs from challenge and ex vivo detection of IFNγ responses against several genotype 2 strains

A PRRSV GP5-Mosaic vaccine: Protection of pigs from challenge and ex vivo detection of IFNγ responses against several genotype 2 strains

Activation of pro- and anti-inflammatory responses in lung tissue injury during the acute phase of PRRSV-1 infection with the virulent strain Lena

The PRRSV-Specific Memory B Cell Response Is Long-Lived in Blood and Is Boosted During Live Virus Re-exposure

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