Replication of infectious bronchitis virus (IBV) Delmarva (DMV)/1639 variant in primary and secondary lymphoid organs leads to immunosuppression in chickens

Najimudeen, Shahnas M.; Abd-Elsalam, Reham M.; Ranaweera, Hiruni A.; Isham, Ishara M.; Hassan, Mohamed S.H.; Farooq, Muhammad; Abdul-Careem, Mohamed Faizal

doi:10.1016/j.virol.2023.109852

Cited by 7 publications

(14 citation statements)

References 64 publications

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“…Similar to the results for our cTEC data, KEGG pathway analyses indicated enrichment for the innate immune response. Once again, the enrichment of the cytokine–cytokine interaction pathway for all in vivo treatment groups is not surprising given that the significant involvement of pro-inflammatory cytokines during IBV infection has been well documented [ 7 , 128 , 129 , 130 , 131 ].…”

Section: Discussionmentioning

confidence: 99%

“…In older chickens and in laying hens, respiratory signs can be mild or even absent [ 1 ]. Although initial infection typically occurs in the epithelial layer of the upper respiratory tract, IBV can disseminate and infect the gastrointestinal, renal, reproductive, and immune systems [ 5 , 6 , 7 , 8 , 9 , 10 ], potentially via the lymph or blood [ 6 , 11 , 12 ]. Depending on the IBV strain, this can lead to other clinical and pathological manifestations, such as nephritis [ 13 ], a decline in egg production and quality of the egg and egg shell in layer/breeder flocks [ 14 , 15 , 16 ], and a depletion of immune cells [ 7 ].…”

Section: Introductionmentioning

confidence: 99%

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Host Immune Response Modulation in Avian Coronavirus Infection: Tracheal Transcriptome Profiling In Vitro and In Vivo

O’Dowd,

Isham,

Vatandour

et al. 2024

Viruses

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Infectious bronchitis virus (IBV) is a highly contagious Gammacoronavirus causing moderate to severe respiratory infection in chickens. Understanding the initial antiviral response in the respiratory mucosa is crucial for controlling viral spread. We aimed to characterize the impact of IBV Delmarva (DMV)/1639 and IBV Massachusetts (Mass) 41 at the primary site of infection, namely, in chicken tracheal epithelial cells (cTECs) in vitro and the trachea in vivo. We hypothesized that some elements of the induced antiviral responses are distinct in both infection models. We inoculated cTECs and infected young specific pathogen-free (SPF) chickens with IBV DMV/1639 or IBV Mass41, along with mock-inoculated controls, and studied the transcriptome using RNA-sequencing (RNA-seq) at 3 and 18 h post-infection (hpi) for cTECs and at 4 and 11 days post-infection (dpi) in the trachea. We showed that IBV DMV/1639 and IBV Mass41 replicate in cTECs in vitro and the trachea in vivo, inducing host mRNA expression profiles that are strain- and time-dependent. We demonstrated the different gene expression patterns between in vitro and in vivo tracheal IBV infection. Ultimately, characterizing host–pathogen interactions with various IBV strains reveals potential mechanisms for inducing and modulating the immune response during IBV infection in the chicken trachea.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Host Immune Response Modulation in Avian Coronavirus Infection: Tracheal Transcriptome Profiling In Vitro and In Vivo

O’Dowd,

Isham,

Vatandour

et al. 2024

Viruses

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“…Activation of these receptors initiates intracellular signalling cascades that culminate in the upregulation of COX-2 gene expression [9, 10]. It is pertinent to note that IBV inoculation of chickens led to an increase in COX-2 mRNA expression within the spleen and thymus, as reported in a recent study [29]. Additionally, in mature chickens, IBV infection elicited heightened levels of both COX-2 mRNA expression and PGE2 production in the uterine mucosa [24].…”

Section: Discussionmentioning

confidence: 99%

“…Real-time quantitative polymerase chain reaction (qPCR) (CFX Opus Realtime PCR systems, BioRAD, USA) assay was used for amplifying the IBV genome load and immune gene mRNA expressions in 96-well plates (VWR, AB, Canada). All samples were run in duplicate following the reaction protocol: 95 °C for 20 seconds (s), 39 cycles of extension/amplification 95 °C for 3 s, and 60 °C for 30 s, and then annealing at 95 °C for 10 s. The primer sequences used were published previously [29]. SYBR green qPCR assay format was used and included three segment melt-curve analyses at 95 °C for 3 s, 65 °C for 5 s, 9 °C for 5 s, respectively.…”

Section: Methodsmentioning

confidence: 99%

“…In an in vivo study involving the IBV DMV/1639 strain, it was shown that IBV replicates in both the primary and secondary immune organs of newly hatched chicks, resulting in significant structural alterations correlating with augmented COX-2 mRNA expression in the spleen and thymus [29]. Moreover, in mature chickens, IBV inoculation resulted in elevated mRNA expression of COX-2 and heightened levels of PGE2 in the uterine mucosa [30].…”

Section: Introductionmentioning

confidence: 99%

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Cyclooxygenase-2/prostaglandin E2 pathway regulates infectious bronchitis virus replication in avian macrophages

Mahmoud,

Farooq,

Isham

et al. 2024

Journal of General Virology

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Infectious bronchitis virus (IBV) is a significant respiratory pathogen that affects chickens worldwide. As an avian coronavirus, IBV leads to productive infection in chicken macrophages. However, the effects of IBV infection in macrophages on cyclooxygenase-2 (COX-2) expression are still to be elucidated. Therefore, we investigated the role of IBV infection on the production of COX-2, an enzyme involved in the synthesis of prostaglandin E2 (PGE2) in chicken macrophages. The chicken macrophage cells were infected with two IBV strains, and the cells and culture supernatants were harvested at predetermined time points to measure intracellular and extracellular IBV infection. IBV infection was quantified as has been the COX-2 and PGE2 productions. We found that IBV infection enhances COX-2 production at both mRNA and protein levels in chicken macrophages. When a selective COX-2 antagonist was used to reduce the COX-2 expression in macrophages, we observed that IBV replication decreased. When IBV-infected macrophages were treated with PGE2 receptor (EP2 and EP4) inhibitors, IBV replication was reduced. Upon utilizing a selective COX-2 antagonist to diminish PGE2 expression in macrophages, a discernible decrease in IBV replication was observed. Treatment of IBV-infected macrophages with a PGE2 receptor (EP2) inhibitor resulted in a reduction in IBV replication, whereas the introduction of exogenous PGE2 heightened viral replication. Additionally, pretreatment with a Janus-kinase two antagonist attenuated the inhibitory effect of recombinant chicken interferon (IFN)-γ on viral replication. The evaluation of immune mediators, such as inducible nitric oxide (NO) synthase (iNOS), NO, and interleukin (IL)−6, revealed enhanced expression following IBV infection of macrophages. In response to the inhibition of COX-2 and PGE2 receptors, we observed a reduction in the expressions of iNOS and IL-6 in macrophages, correlating with reduced IBV infection. Overall, IBV infection increased COX-2 and PGE2 production in addition to iNOS, NO, and IL-6 expression in chicken macrophages in a time-dependent manner. Inhibition of the COX-2/PGE2 pathway may lead to increased macrophage defence mechanisms against IBV infection, resulting in a reduction in viral replication and iNOS and IL-6 expressions. Understanding the molecular mechanisms underlying these processes may shed light on potential antiviral targets for controlling IBV infection.

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Cyclooxygenase-2/prostaglandin E2 pathway orchestrates the replication of infectious bronchitis virus in chicken tracheal explants

Mahmoud,

Ali,

Farooq

et al. 2024

Microbiol Spectr

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In this study, we investigated the localized pathogenesis of infectious bronchitis virus (IBV) in chicken tracheal organ cultures (TOCs), focusing on the role of inducible cyclooxygenase (COX-2). Two divergent IBV strains, respiratory Connecticut (Conn) A5968 and nephropathogenic Delmarva (DMV)/1639, were studied at 6, 12, 24, and 48 hours post-infection (hpi). Various treatments including exogenous prostaglandin (PGE)2, a selective COX-2 antagonist (SC-236), and inhibitors of PGE2 receptors and Janus kinase (JAK) were administered. IBV genome load and antigen expression were quantified using real-time quantitative PCR and immunohistochemistry. COX-2, interferon (IFN)-α, IFN-β, interleukin (IL)−1β, IL-6, and inducible nitric oxide synthase (iNOS) expressions were measured, along with PGE2 and COX-2 concentrations. IBV genome load and protein expression peaked at 12 and 24 hpi, respectively. Conn A5968-infected TOCs exhibited continuous COX-2 expression for up to 24 hpi, extended PGE2 production up to 48 hpi, and reduced inflammatory cytokine expression. In contrast, DMV/1639-infected TOCs displayed heightened inflammatory cytokine expression, brief COX-2 expression, and PGE2 production. Treatment with IFN-γ, SC-236, PGE2 receptor inhibitors, or JAK inhibitors reduced IBV infection and lesion scores, whereas exogenous PGE2 or IFN-γ pretreatment with a JAK-2 inhibitor augmented infection. These findings shed light on the innate immune regulation of IBV infection in the trachea, highlighting the involvement of the COX-2/PGE2 pathway. IMPORTANCE Understanding the localized pathogenesis of infectious bronchitis virus (IBV) within the trachea of chickens is crucial for developing effective control strategies against this prevalent poultry pathogen. This study sheds light on the role of inducible cyclooxygenase (COX-2) and prostaglandin (PGE)2 in IBV pathogenesis using chicken tracheal organ culture (TOC) models. The findings reveal distinct patterns of COX-2 expression, PGE2 production, and immune responses associated with different IBV strains, highlighting the complexity of host-virus interactions. Furthermore, the identification of specific inhibitors targeting the COX-2/PGE2 pathway and Janus kinase-signal transducer and activator of transcription (JAK-STAT) signaling pathway provides potential therapeutic avenues for mitigating IBV infection in poultry. Overall, this study contributes to our understanding of the innate immune regulation of IBV infection within the trachea, laying the groundwork for the development of targeted interventions to control IBV outbreaks in poultry populations.

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Replication of infectious bronchitis virus (IBV) Delmarva (DMV)/1639 variant in primary and secondary lymphoid organs leads to immunosuppression in chickens

Cited by 7 publications

References 64 publications

Host Immune Response Modulation in Avian Coronavirus Infection: Tracheal Transcriptome Profiling In Vitro and In Vivo

Host Immune Response Modulation in Avian Coronavirus Infection: Tracheal Transcriptome Profiling In Vitro and In Vivo

Cyclooxygenase-2/prostaglandin E2 pathway regulates infectious bronchitis virus replication in avian macrophages

Cyclooxygenase-2/prostaglandin E2 pathway orchestrates the replication of infectious bronchitis virus in chicken tracheal explants

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