Coinfection with porcine circovirus type 2 and Streptococcus suis serotype 2 enhances pathogenicity by dysregulation of the immune responses in piglets

Wang, Qing; Zhou, Hong; Hao, Qinfang; Li, Minxue; Liu, Junchi; Fan, Hongjie

doi:10.1016/j.vetmic.2020.108653

Cited by 23 publications

(24 citation statements)

References 32 publications

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“…Similarly, PCV1 is not known to cause disease in pigs and many pigs infected with PCV2 do not develop severe lesions. There is also an indication that infection with circoviruses tends to lead to more severe outcomes in instances of co-infection [2][3][4][5][6] . Analysis of additional cases would be useful to establish a potential association between the presence of the virus and clinical disease.…”

Section: Resultsmentioning

confidence: 99%

“…bird and feather disease virus (BFDV)) 1 . Infection with other circoviruses appear to be subclinical, but may be immunosuppressive and increase disease severity with co-infecting pathogens [2][3][4][5][6] . The two current genera within the family Circoviridae, Circovirus and Cyclovirus, are distinguished by two elements: the length of the intergenic region and the position of the origin of replication in relation to the coding regions 7 .…”

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confidence: 99%

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Discovery and comparative genomic analysis of elk circovirus (ElkCV), a novel circovirus species and the first reported from a cervid host

Fisher¹,

Harrison²,

Nebroski³

et al. 2020

Sci Rep

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The complete genome sequence of a novel circovirus (elk circovirus (ElkCV) Banff/2019) was determined via high throughput sequencing of liver tissue from a euthanized Rocky Mountain elk (Cervus canadensis nelsoni) from Alberta, Canada. The genome is circular and 1,787 nucleotides long, with two major ORFs encoding predicted proteins. Comparative genomic analysis to 4,164 publicly available complete and near complete circovirus genomes showed that ElkCV shares approximately 65% pairwise genome-wide nucleotide identity with the most closely related circovirus species, porcine circoviruses (PCV) 1 and 2 and bat-associated circovirus (BatACV) 11. ElkCV features a stem-loop within the origin of replication region characteristic of circoviruses. However, it differs from those found in PCV1, PCV2 and BatACV11 since it has a longer stem and contains hexamer repeats that overlap the stem in opposing orientations. Interestingly, stem-loop structures of similar length featuring repeats in a similar position and orientation are also seen in some avian circoviruses. Based on the demarcation threshold established by the International Committee on Taxonomy of Viruses (ICTV) for members of Circoviridae (80% pairwise genome-wide nucleotide identity), ElkCV represents a novel species and is the first complete circovirus genome reported from a cervid host.

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Section: Resultsmentioning

confidence: 99%

mentioning

confidence: 99%

Discovery and comparative genomic analysis of elk circovirus (ElkCV), a novel circovirus species and the first reported from a cervid host

Fisher¹,

Harrison²,

Nebroski³

et al. 2020

Sci Rep

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“…To explore the roles of mitogen-activated protein kinases (MAPK) and nuclear factor-kappa B (NF-κB) signaling pathways in cytokine production, STEC were pretreated with different inhibitors for 1 h. The infection time of HPS4-YC was 12 h. The inhibitors used were as follows: SB203580 (p38 inhibitor, MCE, USA), U0126 (ERK inhibitor, MCE, USA), SP600125 (JNK inhibitor, MCE, USA), and BAY11-7082 (NF-κB inhibitor). The concentration of inhibitor used was 10 μM, based on a previously published reference [ 20 ]. STEC treated with equal volumes of DMSO served as controls.…”

Section: Methodsmentioning

confidence: 99%

Glaesserella parasuis serotype 4 HPS4-YC disrupts the integrity of the swine tracheal epithelial barrier and facilitates bacterial translocation

Wang

Chang

Liu

et al. 2021

Vet Res

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Glaesserella parasuis (G. parasuis) is a commensal bacterium in the upper respiratory tract of pigs that can also cause the swine Glässer disease, which induces an intensive inflammatory response and results in significant economic losses to the swine industry worldwide. G. parasuis can cause disease through infection of the respiratory tract, resulting in systemic infection, but the mechanism is largely unknown. Recently we showed that Glaesserella parasuis serotype 4 (GPS4) increased swine tracheal epithelial barrier permeability, resulting in easier bacterial translocation. Tight junction proteins (TJ) play a crucial role in maintaining the integrity and impermeability of the epithelial barrier. GPS4 decreased the expression of the TJ ZO-1 and occludin in swine tracheal epithelial cells (STEC). Furthermore, the proinflammatory cytokines IL-6, IL-8 and TNF-α were significantly upregulated in GPS4-infected STEC, and both the MAPK and NF-κB signaling pathways were activated and contributed to the expression of TNF-α. We demonstrate that the production of proinflammatory cytokines, especially TNF-α, during GPS4 infection was involved in barrier dysfunction. Additionally, animal challenge experiments confirmed that GPS4 infection downregulated TJ in the lungs of piglets and induced a severe inflammatory response. In general, G. parasuis infection downregulated the expression of TJ and induced massive secretion of proinflammatory cytokines, resulting in epithelial barrier disruption and favoring bacterial infection. This study allowed us to better understand the mechanism by which G. parasuis crosses the respiratory tract of pigs.

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“…For example, influenza virus and bacterial pneumonia combined are among the most deadly infection in human cases (1,(4)(5)(6). Swine viruses such as porcine reproductive and respiratory syndrome virus (PRRSV) or PCV2 infection often predisposes pigs to bacterial coinfection (7)(8)(9)(10)(11)(12). However, how the host immune responses to one pathogen alters the immune response to another infectious agent in host-pathogen interactions remain largely unclear.…”

Section: Introductionmentioning

confidence: 99%

“…Notably, concurrent infections with other swine pathogens are usually seen in most field PCVAD cases, which exacerbates the pathogenesis of diseases (13,(16)(17)(18). The most frequently observed bacteria in PCVAD cases are Actinobacillus pleuropneumoniae (APP), Glaesserella parasuis and Streptococcus suis (9,10,15,19,20). As the smallest virus known to infect mammal, PCV2 has a single-strand circular DNA genome approximately 1.7 kb in size and preferentially targets the swine immune systems.…”

Section: Introductionmentioning

confidence: 99%

Macrophage Polarization Modulated by Porcine Circovirus Type 2 Facilitates Bacterial Coinfection

Zhang

Yin

et al. 2021

Front. Immunol.

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Polarization of macrophages to different functional states is important for mounting responses against pathogen infections. Macrophages are the major target cells of porcine circovirus type 2 (PCV2), which is the primary causative agent of porcine circovirus–associated disease (PCVAD) leading to immense economic losses in the global swine industry. Clinically, PCV2 is often found to increase risk of other pathogenic infections yet the underlying mechanisms remain to be elusive. Here we found that PCV2 infection skewed macrophages toward a M1 status through reprogramming expression of a subset of M1-associated genes and M2-associated genes. Mechanistically, induction of M1-associated genes by PCV2 infection is dependent on activation of nuclear factor kappa B (NF-κB) and c-jun N-terminal kinase (JNK) signaling pathways whereas suppression of M2-associated genes by PCV2 is via inhibiting expression of jumonji domain containing-3 (JMJD3), a histone 3 Lys27 (H3K27) demethylase that regulates M2 activation of macrophages. Finally, we identified that PCV2 capsid protein (Cap) directly inhibits JMJD3 transcription to restrain expression of interferon regulatory factor (IRF4) that controls M2 macrophage polarization. Consequently, sustained infection of PCV2 facilitates bacterial infection in vitro. In summary, these findings showed that PCV2 infection functionally modulated M1 macrophage polarization via targeting canonical signals and epigenetic histone modification, which contributes to bacterial coinfection and virial pathogenesis.

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Coinfection with porcine circovirus type 2 and Streptococcus suis serotype 2 enhances pathogenicity by dysregulation of the immune responses in piglets

Cited by 23 publications

References 32 publications

Discovery and comparative genomic analysis of elk circovirus (ElkCV), a novel circovirus species and the first reported from a cervid host

Discovery and comparative genomic analysis of elk circovirus (ElkCV), a novel circovirus species and the first reported from a cervid host

Glaesserella parasuis serotype 4 HPS4-YC disrupts the integrity of the swine tracheal epithelial barrier and facilitates bacterial translocation

Macrophage Polarization Modulated by Porcine Circovirus Type 2 Facilitates Bacterial Coinfection

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