Molecular and Cellular Mechanisms for PRRSV Pathogenesis and Host Response to Infection

An, Tong Qing; Li, Jiang Nan; Su, Chih-Chung; Yoo, Dongwan

doi:10.1016/j.virusres.2020.197980

Cited by 85 publications

(74 citation statements)

References 194 publications

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“…To successfully fight against PRRSV infection, macrophages have evolved various strategies to regulate antiviral responses, such as regulating the production of IFN-α/β [17]. The previous evidence suggested that PRRSV was susceptible to IFNs [18], whereas PRRSV-mediated suppression of IFNs production helped the virus circumvent the host antiviral responses [19]. Besides, the pro-inflammatory cytokines including IL-1, IL-6, IL-8, and TNF-α mainly produced in PAMs after virus invasion, play critical roles in infection and pathogenesis of PRRSV [20][21][22][23].…”

Section: Introductionmentioning

confidence: 99%

Unveiling the long non-coding RNA profile of porcine reproductive and respiratory syndrome virus-infected porcine alveolar macrophages

Gao

Pan

et al. 2021

BMC Genomics

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Background Long noncoding RNA (lncRNA) is highly associated with inflammatory response and virus-induced interferon production. By far the majority of studies have focused on the immune-related lncRNAs of mice and humans, but the function of lncRNAs in porcine immune cells are poorly understood. Porcine reproductive and respiratory syndrome virus (PRRSV) impairs local immune responses in the lungs of nursery and growing pigs, whereas the virus triggers the inflammatory responses. Porcine alveolar macrophage (PAM) is the primary target cell of PRRSV, thus PRRSV is used as an in vitro model of inflammation. Here, we profiled lncRNA and mRNA repertories from PRRSV-infected PAMs to explore the underlying mechanism of porcine lncRNAs in regulating host immune responses. Results In this study, a total of 350 annotated lncRNAs and 1792 novel lncRNAs in PAMs were identified through RNA-seq analysis. Among them 86 differentially expressed (DE) lncRNAs and 406 DE protein-coding mRNAs were identified upon PRRSV incubation. GO category and KEGG pathway enrichment analyses revealed that these DE lncRNAs and mRNAs were mainly involved in inflammation- and pathogen infection-induced pathways. The results of dynamic correlated expression networks between lncRNAs and their predicted target genes uncovered that numerous lncRNAs, such as XLOC-022175, XLOC-019295, and XLOC-017089, were correlated with innate immune genes. Further analysis validated that these three lncRNAs were positively correlated with their predicted target genes including CXCL2, IFI6, and CD163. This study suggests that porcine lncRNAs affect immune responses against PRRSV infection through regulating their target genes in PAMs. Conclusion This study provides both transcriptomic and epigenetic status of porcine macrophages. In response to PRRSV infection, comprehensive DE lncRNAs and mRNAs were profiled from PAMs. Co-expression analysis demonstrated that lncRNAs are emerging as the important modulators of immune gene activities through their critical influence upon PRRSV infection in porcine macrophages.

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Section: Introductionmentioning

confidence: 99%

Unveiling the long non-coding RNA profile of porcine reproductive and respiratory syndrome virus-infected porcine alveolar macrophages

Gao

Pan

et al. 2021

BMC Genomics

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“…Firstly, as the previous studies have reported, low pathogenic PRRSV-like CHsx1401 enhanced the production of pro-inflammatory cytokines including IL-1, IL-6 and TNF-α in PAMs and serum [ 40 ], which could inhibit infection of other pathogens through the activation of NF-КB pathway or STAT pathway [ 34 ]. Besides, upon the PRRSV infection, GLUT2 mRNA abundance and sucrase, maltase, and Na+/K+ adenosine triphosphatase activities in the intestines had increased, and the changed intestinal microenvironment might suppress PDCoV infection in the epithelial cells [ 41 , 42 ]. Additionally, PRRSV infection might inhibit the secretion of trypsin based on the fact that PRRSV infection could induce the occurrence of pancreatitis [ 43 ] and the reduced trypsin might down-regulate the expression levels of receptors for PDCoV entry.…”

Section: Discussionmentioning

confidence: 99%

Attenuation of porcine deltacoronavirus disease severity by porcine reproductive and respiratory syndrome virus coinfection in a weaning pig model

Zhou

Zhang

et al. 2021

Virulence

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Porcine deltacoronavirus (PDCoV) is a potentially emerging zoonotic pathogen that causes severe diarrhea in young pigs, with a risk of fatal dehydration. Its pathogenicity on neonatal piglet has been previously reported, however, it is less known if the coinfection with immunosuppressive pathogens can influence PDCoV disease manifestation. Here, a coinfection model of PDCoV and porcine reproductive and respiratory syndrome virus (PRRSV), a global-spread immunosuppressive virus, was set to study their interaction. Weaning pigs in the coinfection group were intranasally inoculated with PRRSV NADC30-like virus and latterly orally inoculated with PDCoV at three day-post-inoculation (DPI). Unexpectedly, compared with pigs in the PDCoV single-infected group, the coinfected pigs did not show any obvious diarrhea, as PDCoV fecal shedding, average daily weight gain (ADWG), gross and microscopic lesions and PDCoV IHC scores consistently indicated that PRRSV coinfection lessened PDCoV caused diarrhea. Additionally, three proinflammatory cytokines TNF-α, IL-1 and IL-6, which can be secreted by PRRSV infected macrophages, were detected to be highly expressed at the intestine from both PRRSV infected groups. By adding to PDCoV-infected cells, these three cytokines were further confirmed to be able to inhibit the PDCoV replication post its cellular entry. Meanwhile, the inhibition effect of the supernatant from PRRSV-infected PAMs could be obviously blocked by the antagonist of these three cytokines. In conclusion, PRRSV coinfection increased TNF-α, IL-1, and IL-6 in the microenvironment of intestines, which inhibits the PDCoV proliferation, leading to lessened severity of diarrhea. The findings provide some new insight into the pathogenesis and replication regulation of PDCoV.

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“…The last stage is critically dependent on CD163, a scavenger receptor cysteine-rich (SRCR) family for hemoglobin clearance, which is the most specific and indispensable receptor for PRRSV entry and infection both in vitro and in vivo [ 8 , 12 , 59 ]. Additionally, the viral GP2 and GP4 glycoproteins bind to CD163 [ 13 ]. Moreover, a study has shown that CD163 interacts with GP3 and GP5 in addition to the known interactions with GP4 and GP2, and co-immunoprecipitation (co-IP) analysis indicated that the SRCR5-domain deletion of CD163 loses its interaction with viral GP2, GP3, and GP5, and thus blocks virus uncoating in the early endosomes [ 17 ].…”

Section: The Process Of the Prrsv Entry And Infectionmentioning

confidence: 99%

“…The PRRSV is mainly divided into two genotypes: type 1 (represented by the European strain Lelystad Virus) and type 2 (represented by the North American strain VR-2332), and both PRRSV genotypes have only 50–60% nucleotide identity [ 6 , 13 ]. In addition to the genotype differences between PRRSV-1 and PRRSV-2, the host immune responses have been shown to differ, sometimes considerably due to their biological differences including pathogenicity ( Table 1 ).…”

Section: Introductionmentioning

confidence: 99%

The Function of the PRRSV–Host Interactions and Their Effects on Viral Replication and Propagation in Antiviral Strategies

Yang

et al. 2021

Vaccines

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Porcine reproductive and respiratory syndrome virus (PRRSV) affects the global swine industry and causes disastrous economic losses each year. The genome of PRRSV is an enveloped single-stranded positive-sense RNA of approximately 15 kb. The PRRSV replicates primarily in alveolar macrophages of pig lungs and lymphatic organs and causes reproductive problems in sows and respiratory symptoms in piglets. To date, studies on how PRRSV survives in the host, the host immune response against viral infections, and pathogenesis, have been reported. PRRSV vaccines have been developed, including inactive virus, modified live virus, attenuated live vaccine, DNA vaccine, and immune adjuvant vaccines. However, there are certain problems with the durability and effectiveness of the licensed vaccines. Moreover, the high variability and fast-evolving populations of this RNA virus challenge the design of PRRSV vaccines, and thus effective vaccines against PRRSV have not been developed successfully. As is well known, viruses interact with the host to escape the host’s immune response and then replicate and propagate in the host, which is the key to virus survival. Here, we review the complex network and the mechanism of PRRSV–host interactions in the processes of virus infection. It is critical to develop novel antiviral strategies against PRRSV by studying these host–virus interactions and structures to better understand the molecular mechanisms of PRRSV immune escape.

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Molecular and Cellular Mechanisms for PRRSV Pathogenesis and Host Response to Infection

Cited by 85 publications

References 194 publications

Unveiling the long non-coding RNA profile of porcine reproductive and respiratory syndrome virus-infected porcine alveolar macrophages

Unveiling the long non-coding RNA profile of porcine reproductive and respiratory syndrome virus-infected porcine alveolar macrophages

Attenuation of porcine deltacoronavirus disease severity by porcine reproductive and respiratory syndrome virus coinfection in a weaning pig model

The Function of the PRRSV–Host Interactions and Their Effects on Viral Replication and Propagation in Antiviral Strategies

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