Predicted peptides from non-structural proteins of porcine reproductive and respiratory syndrome virus are able to induce IFN-γ and IL-10 (original) (raw)
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Porcine reproductive and respiratory syndrome virus (PRRSV) is currently one of the most important viruses affecting the swine industry worldwide. Despite the large number of papers published each year, the participation of non-structural proteins (nsps) in the immune response is not completely clear. nsps have been involved in the host innate immune response, specifically, nsp1α/β, nsp2, nsp4 and nsp11 have been associated with the immunomodulation capability of the virus. To date, only participation by nsp1, nsp2, nsp4 and nsp7 in the humoral immune response has been reported, with the role of other nsps being overlooked. Furthermore, nsp1, nsp2, nsp5, nsp7 nsp9, nsp10, nsp11 have been implicated in the induction of IFN-γ and probably in the development of the cell-mediated immune response. This review discusses recent reports involving the participation of nsps in the modulation of the innate immune response and their role in the induction of both the humoral and cellular immune responses.
Virus Research, 2012
Porcine reproductive and respiratory syndrome virus (PRRSV) is a significant swine pathogen which exhibits considerable sequence diversity. In an attempt to identify highly conserved T-cell epitopes contained in proteins of this virus, we examined heptadecamer peptides spanning the sequence of the PRRSV nonstructural proteins (NSPs) 9 and 10, both of which are highly conserved, for their ability to elicit a recall proliferative and interferon-gamma response in peripheral blood mononuclear cells obtained from pigs immunized against the type-II PRRSV strain FL-12. These studies led to the identification of four peptides, two from each NSP9 and NSP10 that appear to contain T-cell epitopes. Comparison of the amino acid sequence of these four peptide sequences to the analogous sequences from a diverse sample of type-II PRRSV strains indicated that these sequences are highly conserved and thus contain highly conserved T-cell epitopes. The identified epitopes may be important in the formulation of immunogens to provide broad cross-protection against diverse PRRSV strains.
Frontiers in immunology, 2016
The porcine reproductive and respiratory syndrome virus (PRRSV) is the cause of one of the most economically important diseases affecting swine worldwide. Efforts to develop a next-generation vaccine have largely focused on envelope glycoproteins to target virus-neutralizing antibody responses. However, these approaches have failed to demonstrate the necessary efficacy to progress toward market. T cells are crucial to the control of many viruses through cytolysis and cytokine secretion. Since control of PRRSV infection is not dependent on the development of neutralizing antibodies, it has been proposed that T cell-mediated immunity plays a key role. Therefore, we hypothesized that conserved T cell antigens represent prime candidates for the development a novel PRRS vaccine. Antigens were identified by screening a proteome-wide synthetic peptide library with T cells from cohorts of pigs rendered immune by experimental infections with a closely related (subtype 1) or divergent (subtyp...
Journal of General Virology, 2003
Several lines of evidence suggest that porcine reproductive and respiratory syndrome virus (PRRSV) may have immunomodulatory effects on the host immune system. To determine the effect of PRRSV on cytokine production, a multiplex PCR was established. This allowed a semiquantitative analysis of IFN-g, IL-2, IL-4, IL-10 and glyceraldehyde 3-phosphate dehydrogenase (GAPDH) gene expression levels from porcine peripheral blood mononuclear cells (PBMCs). These results showed that both live and inactivated PRRSV predominantly upregulated IL-10 gene expression in porcine PBMCs. In addition, when PBMCs from pigs immunized previously with classical swine fever virus (CSFV) vaccine were cultivated with the recall antigen, CSFV, in the presence of PRRSV, significant upregulation of IL-10 gene expression and reduction of IFN-g gene expression were observed. These findings indicated that the presence of PRRSV in the culture could affect recall antigen response. This study implies that the induction of IL-10 production may be one of the strategies used by PRRSV to modulate host immune responses.
Virology, 2006
Immunization of piglets with two different European-type modified live vaccines against porcine reproductive and respiratory syndrome (PRRS) virus produced different outcomes. After vaccination, pigs became viremic (42 days), neutralizing antibodies did not develop, and frequencies of virus-specific gamma-interferon-secreting cells (IFN-γ-SC) were low. Levels of interleukin-10 (IL-10) produced by peripheral blood mononuclear cells (PBMC) seemed to inversely correlate with interferon-gamma responses. After a challenge with a virulent Spanish strain, one vaccine (V3) protected piglets against viremia while the other (V1) did not. The vaccine V3 induced the highest IFN-γ-SC frequencies. IL-2, IL-4 or transforming growth factor-beta responses were not detected at any time for neither of the vaccines. In contrast, haptoglobin rose in sera of viremic pigs after the challenge. These results indicated a strong involvement of IFN-γ, and maybe IL-10, in the development of immunity against PRRS virus.
Veterinary Immunology and Immunopathology, 2012
Despite the numerous studies carried out, the mechanisms used by porcine reproductive and respiratory syndrome (PRRS) virus (PRRSV) to impair the host immune response are not yet clear. The aim of this study was to determine the expression of IL-12, IL-10, IFN-␣ and IFN-␥ in lymphoid organs of PRRSV experimentally-infected pigs. Twenty eight piglets were inoculated with PRRSV field isolate 2982 and killed in batches of four at 3, 7, 10, 14, 17, 21 and 24 days post-inoculation (dpi). Control animals were mock-inoculated and killed at the end of the study. Samples from mediastinal and retropharyngeal lymph nodes and tonsil were collected and fixed for histopathological and immunohistochemical analyses. PRRSV antigen was mainly detected in the cytoplasm of macrophages, displaying a bimodal expression with a first peak at 3-7 dpi and a second peak at 14 dpi. The expression of IFN-␣ showed an early enhancement at 3 dpi, and both IL-12 and IFN-␥ displayed a similar trend in all the lymphoid organs analysed, showing an increase at 3-7 dpi and at 14-17 dpi. On the other hand, the expression of IL-10 was lower than the one observed for the other cytokines. The expression of IL-10 compared with the higher expression of IL-12, IFN-␣ and IFN-␥ detected in this study, indicates that other mechanisms besides the expression of IL-10 play a role in the inducement of an erratic host immune response. Taking into account the enhanced expression of IFNs together with the detection of PRRSV antigen until the end of the study in the examined lymphoid organs, further studies are being conducted to rule out a down-regulation in IFN signalling pathway.
Archives of Virology, 1999
The identification of antigens recognized by T cell responses has become fundamental for developing effective immunizations against viral infections. Lymphocyte proliferation and delayed-type hypersensitivity responses to porcine reproductive and respiratory syndrome virus (PRRSV) infection have been demonstrated. However, the polypeptide specificity of T cell responses to PRRSV is unknown. To identify the PRRSV polypeptides recognized by porcine lymphocytes two approaches were employed. First polypeptides of purified virions were separated by SDS-PAGE and particle suspensions obtained from nitrocellulose blots were used as antigens. Second, the polypeptides encoded by ORFs 2, 4, 5, 6, and 7 of the strain VR-2 332 were expressed as fusion proteins with a histidine tag in mammalian cells, using vaccinia virus as expression system. Significant antigen-specific proliferation responses to the matrix and envelope proteins from purified virions were obtained. This finding was supported by specific and dose-dependent proliferation responses to the recombinant polypeptides encoded by ORF2, 5 and 6 detected in virus-infected but not in control pigs. These results demonstrate that T-cell responses can be detected to individual PRRSV polypeptides. The greater response to the product of ORF6 than to the other PRRSV polypeptides indicates that the viral matrix polypeptide may have a major role in cellular immunity.
Virus research, 2010
Porcine reproductive and respiratory syndrome virus (PRRSV) is one of the most costly pathogens for the swine industry. Since its emergence some 20 years ago, much has been learned about the immunobiology of PRRSV. Although vaccines are available, they do not provide full and universal protection against PRRSV infection. In the present review, current knowledge on the virus's immunobiology will be discussed including: role of viral receptors, innate immune response to the virus, regulation of the immune response by PRRSV, and the characteristics and role of adaptive immunity. In addition, some hypotheses for future research in this area are presented.
Vaccines
Luciferase-immunoprecipitation system (LIPS), a liquid phase immunoassay, was used to evaluate antibody responses directed against the structural proteins of PRRSV in pigs that were experimentally infected with virulent PRRSV strains. First, the viral N protein was used as a model antigen to validate the assay. The LIPS results were highly comparable to that of the commercial IDEXX PRRS X3 ELISA. Subsequently, the assay was applied to simultaneously measure antibody reactivity against all eight structural proteins of PRRSV. The highest immunoreactivities were detected against GP3, M, and N proteins while the lowest reactivity was detected against ORF5a protein. Comparative analysis of the kinetics of antibody appearance revealed that antibodies specific to N protein appeared earlier than antibodies against GP3. Finally, the assay was applied to measure immunoreactivities of clinical serum samples against N and GP3. The diagnostic sensitivity of the LIPS with N protein was superior t...
Veterinary Immunology and Immunopathology, 2006
Various vaccine adjuvant candidates were assessed with the modified-live porcine reproductive and respiratory syndrome virus (MLV PRRSV) (Ingelvac 1 PRRS MLV) vaccine. Their influence on humoral-mediated immune (HMI) and cell-mediated immune (CMI) responses as well as protection from virulent PRRSV challenge (MN-184) was evaluated. Ninety seronegative pigs were randomly divided into nine groups of 10 pigs. One group received MLV vaccine alone. Five groups received MLV vaccine with either bacterial endotoxin-derived adjuvant (ET), mixed open reading frame 5 (ORF5) peptides derived from various PRRSV isolates, porcine interferon alpha (IFNa), polyinosinic-polycytidylic acid stabilized with polylysine and carboxymethylcellulose (poly-ICLC), or porcine interleukin-12 (IL-12). One group did not receive MLV vaccine but was immunized with ORF5 peptides conjugated with cholera toxin (ORF5 peptide/CT). Two groups served as challenged and unchallenged non-vaccinated controls. Four-color flow cytometry was utilized to simultaneously identify three major porcine Tcell surface markers (CD4, CD8, and gd TCR) and detect activation marker CD25 (a chain of IL-2 receptor) or intracellular IFNg. The MLV PRRSV vaccine alone successfully primed CD4 À CD8 + gd À T-cells as demonstrated by a significant increase in %IFNg + cells when live PRRSV was used as a recall antigen. Booster immunizations of mixed ORF5 peptides and coadministration of IL-12 with MLV PRRSV vaccine significantly enhanced IFNg expression by some T-cell subsets (CD4 À CD8 + gd + and CD4 À CD8 À gd + for mixed ORF5 peptides and CD4 + CD8 + gd À and CD4 À CD8 + gd + for IL-12). All groups receiving MLV-vaccine with or without adjuvants had reduced lung lesions after challenge. The group immunized with only ORF5 peptide/CT did not have significant T-cell recall responses and was not protected from challenge. Expression of IFNg by several T-cell subsets correlated with reduced lung lesions and viremia, whereas expression of CD25 did not. Expression of www.elsevier.com/locate/vetimm Veterinary Immunology and Immunopathology 109 (2006) 99-115