Comparison of Immune Responses in Pigs Infected with Chinese Highly Pathogenic PRRS Virus Strain HV and North American Strain NADC-20

Li, X.; Galliher-Beckley, Amy; Wang, Lihua; Nietfeld, Jerome C.; Feng, Wen-hai; Shi, Jishu

doi:10.2174/1874357901711010073

Cited by 8 publications

(4 citation statements)

References 26 publications

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“…In our study, IDO1 was highly up-regulated at 6 dpi in both infected groups but mainly in virulent Lena-infected pigs, coinciding with a peak of IFN-g concentration in serum, as previously reported in a parallel study (52). An increase in TNFa serum concentration has been also observed in the early phase of infection by Lena strain (53) as well as by other virulent PRRSV strains (54,55). Interestingly, other immune checkpoints, such as PD-1/PD-L1, CTLA-4 and CD200R1, are associated with IDO-1 expression (49, 50), which is supported in our study by the correlation observed between CTLA4 and IDO1 (r = 0.78), between PD1 and IDO1 (r = 0.54) and between PDL1 and IDO1 (r = 0.65) in the thymus from virulent Lenainfected group.…”

Section: Discussionsupporting

confidence: 90%

Up-Regulation of Immune Checkpoints in the Thymus of PRRSV-1-Infected Piglets in a Virulence-Dependent Fashion

et al. 2021

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Virulent porcine reproductive and respiratory syndrome virus (PRRSV) strains, such as the Lena strain, have demonstrated a higher thymus tropism than low virulent strains. Virulent PRRSV strains lead to severe thymus atrophy, which could be related to marked immune dysregulation. Impairment of T-cell functions through immune checkpoints has been postulated as a strategy executed by PRRSV to subvert the immune response, however, its role in the thymus, a primary lymphoid organ, has not been studied yet. Therefore, the goal of this study was to evaluate the expression of selected immune checkpoints (PD1/PDL1, CTLA4, TIM3, LAG3, CD200R1 and IDO1) in the thymus of piglets infected with two different PRRSV-1 strains. Thymus samples from piglets infected with the low virulent 3249 strain, the virulent Lena strain and mock-infected were collected at 1, 3, 6, 8 and 13 days post-infection (dpi) to analyze PRRSV viral load, relative quantification and immunohistochemical staining of immune checkpoints. PD1/PDL1, CTLA4, TIM3, LAG3 and IDO1 immune checkpoints were significantly up-regulated in the thymus of PRRSV infected piglets, especially in those infected with the virulent Lena strain from 6 dpi onwards. This up-regulation was associated with disease progression, high viral load and cell death. Co-expression of these molecules can affect T-cell development, maturation and selection, negatively regulating the host immune response against PRRSV.

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Section: Discussionsupporting

confidence: 90%

Up-Regulation of Immune Checkpoints in the Thymus of PRRSV-1-Infected Piglets in a Virulence-Dependent Fashion

et al. 2021

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“…Some parameters seem to correlate with the PRRSV virulence phenotype. For example, high fever, anorexia, and lethargy are generally observed in pigs infected with virulent PRRSV strains [20,[53][54][55][56][57][58][59]. Viremia levels have been reported to be higher for infections with virulent PRRSV-1 isolates or PRRSV-2 isolates [53,59,60]; however, the PRRSV-1 isolate SU1-bel induced lower and shorter viremia in comparison with the reference Lelystad isolate, although SU1-bel isolate caused a greater clinical score and gross lung lesions [61].…”

Section: Discussionmentioning

confidence: 99%

In Vivo and In Vitro Characterization of the Recently Emergent PRRSV 1-4-4 L1C Variant (L1C.5) in Comparison with Other PRRSV-2 Lineage 1 Isolates

Rawal,

Almeida,

Gauger

et al. 2023

Viruses

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The recently emerged PRRSV 1-4-4 L1C variant (L1C.5) was in vivo and in vitro characterized in this study in comparison with three other contemporary 1-4-4 isolates (L1C.1, L1A, and L1H) and one 1-7-4 L1A isolate. Seventy-two 3-week-old PRRSV-naive pigs were divided into six groups with twelve pigs/group. Forty-eight pigs (eight/group) were for inoculation, and 24 pigs (four/group) served as contact pigs. Pigs in pen A of each room were inoculated with the corresponding virus or negative media. At two days post inoculation (DPI), contact pigs were added to pen B adjacent to pen A in each room. Pigs were necropsied at 10 and 28 DPI. Compared to other virus-inoculated groups, the L1C.5-inoculated pigs exhibited more severe anorexia and lethargy, higher mortality, a higher fraction of pigs with fever (>40 °C), higher average temperature at several DPIs, and higher viremia levels at 2 DPI. A higher percentage of the contact pigs in the L1C.5 group became viremic at two days post contact, implying the higher transmissibility of this virus strain. It was also found that some PRRSV isolates caused brain infection in inoculation pigs and/or contact pigs. The complete genome sequences and growth characteristics in ZMAC cells of five PRRSV-2 isolates were further compared. Collectively, this study confirms that the PRRSV 1-4-4 L1C variant (L1C.5) is highly virulent with potential higher transmissibility, but the genetic determinants of virulence remain to be elucidated.

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“…Our previous study suggests that there is a negative correlation between high body temperature and the survival time for HP-PRRSV-infected piglets ( 5 ). And high fever is also related to virulence ( 38 ). Thus, it is necessary to explore the mechanisms on how HP-PRRSV triggers high fever in pigs.…”

Section: Discussionmentioning

confidence: 99%

NSP2 Is Important for Highly Pathogenic Porcine Reproductive and Respiratory Syndrome Virus to Trigger High Fever-Related COX-2-PGE2 Pathway in Pigs

Wang

Liu

et al. 2021

Front. Immunol.

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In 2006, atypical porcine reproductive and respiratory syndrome (PRRS) caused by a highly pathogenic PRRSV (HP-PRRSV) strain broke out in China. Atypical PRRS is characterized by extremely high fever and high mortality in pigs of all ages. Prostaglandin E2 (PGE2) derived from arachidonic acid through the activation of the rate-limiting enzyme cyclooxygenase type 1/2 (COX-1/2) plays an important role in fever. Here, we showed that HP-PRRSV infection increased PGE2 production in microglia via COX-2 up-regulation depending on the activation of MEK1-ERK1/2-C/EBPβ signaling pathways. Then, we screened HP-PRRSV proteins and demonstrated that HP-PRRSV nonstructural protein 2 (NSP2) activated MEK1-ERK1/2-C/EBPβ signaling pathways by interacting with 14-3-3ζ to promote COX-2 expression, leading to PGE2 production. Furthermore, we identified that the amino acid residues 500-596 and 658-777 in HP-PRRSV NSP2 were essential to up-regulate COX-2 expression and PGE2 production. Finally, we made mutant HP-PRRS viruses with the deletion of residues 500-596 and/or 658-777, and found out that these viruses had impaired ability to up-regulate COX-2 and PGE2 production in vitro and in vivo. Importantly, pigs infected with the mutant viruses had relieved fever, clinical symptoms, and mortality. These data might help us understand the molecular mechanisms underlying the high fever and provide clues for the development of HP-PRRSV attenuated vaccines.

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Comparison of Immune Responses in Pigs Infected with Chinese Highly Pathogenic PRRS Virus Strain HV and North American Strain NADC-20

Cited by 8 publications

References 26 publications

Up-Regulation of Immune Checkpoints in the Thymus of PRRSV-1-Infected Piglets in a Virulence-Dependent Fashion

Up-Regulation of Immune Checkpoints in the Thymus of PRRSV-1-Infected Piglets in a Virulence-Dependent Fashion

In Vivo and In Vitro Characterization of the Recently Emergent PRRSV 1-4-4 L1C Variant (L1C.5) in Comparison with Other PRRSV-2 Lineage 1 Isolates

NSP2 Is Important for Highly Pathogenic Porcine Reproductive and Respiratory Syndrome Virus to Trigger High Fever-Related COX-2-PGE2 Pathway in Pigs

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