Mechanisms of Adaptive Immunity to Porcine Reproductive and Respiratory Syndrome Virus

Rahe, Michael C.; Murtaugh, Michael P.

doi:10.3390/v9060148

Cited by 56 publications

(53 citation statements)

References 161 publications

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“…NK cells, an important component of the innate host defence system, play a critical role in the resolution of viral infections [31]. In general, the potential roles of NK cells in relation to PRRSV immunity are poorly understood [43,44]. In the current study, two defined NK cell subpopulations were distinguished in PBMC based on an approach similar to one previously described [25].…”

Section: Discussionmentioning

confidence: 91%

Evaluation of local and systemic immune responses in pigs experimentally challenged with porcine reproductive and respiratory syndrome virus

Nazki

Khatun

Jeong

et al. 2020

Vet Res

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The host-associated defence system responsible for the clearance of porcine reproductive and respiratory syndrome virus (PRRSV) from infected pigs is currently poorly understood. To better understand the dynamics of host-pathogen interactions, seventy-five of 100 pigs infected with PRRSV-JA142 and 25 control pigs were euthanized at 3, 10, 21, 28 and 35 days post-challenge (dpc). Blood, lung, bronchoalveolar lavage (BAL) and bronchial lymph node (BLN) samples were collected to evaluate the cellular immune responses. The humoral responses were evaluated by measuring the levels of anti-PRRSV IgG and serum virus-neutralizing (SVN) antibodies. Consequently, the highest viral loads in the sera and lungs of the infected pigs were detected between 3 and 10 dpc, and these resulted in moderate to mild interstitial pneumonia, which resolved accompanied by the clearance of most of the virus by 28 dpc. At peak viremia, the frequencies of alveolar macrophages in infected pigs were significantly decreased, whereas the monocytederived DC/macrophage and conventional DC frequencies were increased, and these effects coincided with the early induction of local T-cell responses and the presence of proinflammatory cytokines/chemokines in the lungs, BAL, and BLN as early as 10 dpc. Conversely, the systemic T-cell responses measured in the peripheral blood mononuclear cells were delayed and significantly induced only after the peak viremic stage between 3 and 10 dpc. Taken together, our results suggest that activation of immune responses in the lung could be the key elements for restraining PRRSV through the early induction of T-cell responses at the sites of virus replication. © The Author(s) 2020. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article' s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article'

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Section: Discussionmentioning

confidence: 91%

Evaluation of local and systemic immune responses in pigs experimentally challenged with porcine reproductive and respiratory syndrome virus

Nazki

Khatun

Jeong

et al. 2020

Vet Res

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“…Besides, as suggested by Loving, Osorio, Murtaugh, and Zuckermann (), this decreased IFN‐α response could be involved in the delayed and low specific immune response characterizing PRRSV infection. Nonetheless, the immunosuppressive potential of PRRSV and its facilitating role for other viral/bacterial co‐infection is still debated (Rahe & Murtaugh, ). Some compelling studies have shown yet that PRRSV infection could alter the immune response to viral infection or vaccination (Van Reeth, Nauwynck, & Pensaert, ; Suradhat et al, ).…”

Section: Introductionmentioning

confidence: 99%

Natural viral co‐infections in pig herds affect hepatitis E virus (HEV) infection dynamics and increase the risk of contaminated livers at slaughter

Salines

Dumarest

Andraud

et al. 2019

Transbound Emerg Dis

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Hepatitis E virus (HEV) is a zoonotic pathogen, in particular genotype 3 HEV is mainly transmitted to humans through the consumption of contaminated pork products. This study aimed at describing HEV infection patterns in pig farms and at assessing the impact of immunomodulating co-infections namely Porcine Reproductive and Respiratory Syndrome Virus (PRRSV) and Porcine Circovirus Type 2 (PCV2), as well as other individual factors such as piglets' immunity and litters' characteristics on HEV dynamics. A longitudinal follow-up was conducted in three farrow-to-finish farms known to be HEV infected. Overall, 360 piglets were individually monitored from birth to slaughter with regular blood and faecal sampling as well as blood and liver samples collected at slaughterhouse. Virological and serological analyses were performed to detect HEV, PCV2 and PRRSV genome and antibodies. The links between 12 explanatory variables and four outcomes describing HEV dynamics were assessed using cox-proportional hazard models and logistic regression. HEV infection dynamics was found highly variable between farms and in a lower magnitude between batches. HEV positive livers were more likely related to short time-intervals between HEV infection and slaughter time (<40 days, OR = 4.1 [3.7-4.5]). In addition to an influence of piglets' sex and sows' parity, the sequence of co-infections was strongly associated with different HEV dynamics: a PRRSV or PCV2/PRRSV pre-or co-infection was associated with a higher age at HEV shedding (Hazard Ratio = 0.3 [0.2-0.5]), as well as a higher age at HEV seroconversion (HR = 0.5 [0.3-0.9] and HR = 0.4 [0.2-0.7] respectively). A PCV2/PRRSV pre-or co-infection was associated with a longer duration of shedding (HR = 0.5 [0.3-0.8]). Consequently, a PRRSV or PCV2/PRRSV pre-or co-infection was strongly associated with a higher risk of having positive livers at slaughter (OR = 4.1 [1.9-8.9] and OR = 6.5 [3.2-13.2] respectively). In conclusion, co-infections with immunomodulating viruses were found to affect HEV dynamics in the farrow-to-finish pig farms that were followed in this study. K E Y W O R D S hepatitis E virus, infection dynamics, PCV2, PRRSV, public health, risk factors | 1931 SALINES Et AL.

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“…genome has nine open reading frames that encode seven structural proteins and 16 nonstructural proteins; all play essential roles in diverse processes related to pathogenesis, such as replication, infection, and virulence (1,3).…”

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confidence: 99%

“…Immunosuppression is the result of several factors, including the perturbation of monocyte/macrophage cell development, a reduction in antiviral and inflammatory cytokines, and an increased secretion of immunosuppressive cytokines (3)(4)(5)(6)(7)(8). PRRSV infection negatively affects expression of MHC and costimulation in monocytederived dendritic cells (MoDCs), thereby suppressing B, T, and NK cell proliferation and differentiation (3,7). Nsp1␤ in the type 2 PRRSV isolate SD95-21 inhibits interferon (IFN) production by restraining double-stranded RNA (dsRNA)-mediated IRF3 phosphorylation and nuclear translocation (4).…”

mentioning

confidence: 99%

Nsp1α of Porcine Reproductive and Respiratory Syndrome Virus Strain BB0907 Impairs the Function of Monocyte-Derived Dendritic Cells via the Release of Soluble CD83

Chen

Bai

Liu

et al. 2018

J Virol

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Porcine reproductive and respiratory syndrome virus (PRRSV), a virulent pathogen of swine, suppresses the innate immune response and induces persistent infection. One mechanism used by viruses to evade the immune system is to cripple the antigen-processing machinery in monocyte-derived dendritic cells (MoDCs). In this study, we show that MoDCs infected by PRRSV express lower levels of the major histocompatibility complex (MHC)-peptide complex proteins TAP1 and ERp57 and are impaired in their ability to stimulate T cell proliferation and increase their production of CD83. Neutralization of sCD83 removes the inhibitory effects of PRRSV on MoDCs. When MoDCs are incubated with exogenously added sCD83 protein, TAP1 and ERp57 expression decreases and T lymphocyte activation is impaired. PRRSV nonstructural protein 1α (Nsp1α) enhances CD83 promoter activity. Mutations in the ZF domain of Nsp1α abolish its ability to activate the CD83 promoter. We generated recombinant PRRSVs with mutations in Nsp1α and the corresponding repaired PRRSVs. Viruses with Nsp1α mutations did not decrease levels of TAP1 and ERp57, impair the ability of MoDCs to stimulate T cell proliferation, or increase levels of sCD83. We show that the ZF domain of Nsp1α stimulates the secretion of CD83, which in turn inhibits MoDC function. Our study provides new insights into the mechanisms of immune suppression by PRRSV. PRRSV has a severe impact on the swine industry throughout the world. Understanding the mechanisms by which PRRSV infection suppresses the immune system is essential for a robust and sustainable swine industry. Here, we demonstrated that PRRSV infection manipulates MoDCs by interfering with their ability to produce proteins in the MHC-peptide complex. The virus also impairs the ability of MoDCs to stimulate cell proliferation, due in large part to the enhanced release of soluble CD83 from PRRSV-infected MoDCs. The viral nonstructural protein 1 (Nsp1) is responsible for upregulating CD83 promoter activity. Amino acids in the ZF domain of Nsp1α (L5-2A, rG45A, G48A, and L61-6A) are essential for CD83 promoter activation. Viruses with mutations at these sites no longer inhibit MoDC-mediated T cell proliferation. These findings provide novel insights into the mechanism by which the adaptive immune response is suppressed during PRRSV infection.

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Mechanisms of Adaptive Immunity to Porcine Reproductive and Respiratory Syndrome Virus

Cited by 56 publications

References 161 publications

Evaluation of local and systemic immune responses in pigs experimentally challenged with porcine reproductive and respiratory syndrome virus

Evaluation of local and systemic immune responses in pigs experimentally challenged with porcine reproductive and respiratory syndrome virus

Natural viral co‐infections in pig herds affect hepatitis E virus (HEV) infection dynamics and increase the risk of contaminated livers at slaughter

Nsp1α of Porcine Reproductive and Respiratory Syndrome Virus Strain BB0907 Impairs the Function of Monocyte-Derived Dendritic Cells via the Release of Soluble CD83

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