Activation of Cytotoxic Lymphocytes and Presence of Regulatory T Cells in the Trachea of Non-Vaccinated and Vaccinated Chickens as a Recall to an Infectious Laryngotracheitis Virus (ILTV) Challenge

While the protective efficacy of the infectious laryngotracheitis virus (ILTV) vaccines is well established, little is known about which components of the immune response are associated with effective resistance and vaccine protection. Early studies have pointed to the importance of the T cell-mediated immune responses. This study aimed to evaluate the activation of cytotoxic T lymphocytes (CTLs) and natural killer (NK) cells and to quantify the presence of regulatory T cells (Tregs) in the larynx–trachea of chickens vaccinated with chicken embryo origin (CEO), tissue culture origin (TCO) and recombinant Herpesvirus of Turkey-laryngotracheitis (rHVT-LT) vaccines after challenge. Our results indicated that CEO vaccine protection was characterized by early CTLs and activated CTLs enhanced responses. TCO and rHVT-LT protection were associated with a moderate increase in resting and activated CTLs followed by an enhanced NK cell response. Tregs increase was only detected in the non-vaccinated challenged group, probably to support healing of the severe trachea epithelial damage. Taken together, our results revealed main differences in the cellular immune responses elicited by CEO, TCO, and rHVT-LT vaccination in the upper respiratory tract after challenge, and that activated CTLs rather than NK cells play a main role in vaccine protection.

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Infectious Laryngotracheitis Virus Viral Chemokine-Binding Protein Glycoprotein G Alters Transcription of Key Inflammatory Mediators In Vitro and In Vivo

Journal of Virology ◽

10.1128/jvi.01534-17 ◽

2017 ◽

Vol 92 (1) ◽

Cited By ~ 5

Author(s):

Mauricio J. C. Coppo ◽

Joanne M. Devlin ◽

Alistair R. Legione ◽

Paola K. Vaz ◽

Sang-Won Lee ◽

...

Keyword(s):

Immune Responses ◽

Binding Protein ◽

Upper Respiratory Tract ◽

Infectious Laryngotracheitis Virus ◽

Glycoprotein G ◽

Infectious Laryngotracheitis ◽

Upper Respiratory ◽

Laryngotracheitis Virus

ABSTRACTInfectious laryngotracheitis virus (ILTV) is an alphaherpesvirus that infects chickens, causing upper respiratory tract disease and significant losses to poultry industries worldwide. Glycoprotein G (gG) is a broad-range viral chemokine-binding protein conserved among most alphaherpesviruses, including ILTV. A number of studies comparing the immunological parameters between infection with gG-expressing and gG-deficient ILTV strains have demonstrated that expression of gG is associated with increased virulence, modification of the amount and the composition of the inflammatory response, and modulation of the immune responses toward antibody production and away from cell-mediated immune responses. The aims of the current study were to examine the establishment of infection and inflammation by ILTV and determine how gG influences that response to infection.In vitroinfection studies using tracheal organ tissue specimen cultures and blood-derived monocytes andin vivoinfection studies in specific-pathogen-free chickens showed that leukocyte recruitment to the site of infection is an important component of the induced pathology and that this is influenced by the expression of ILTV gG and changes in the transcription of the chicken orthologues of mammalian CXC chemokine ligand 8 (CXCL8), chicken CXCLi1 and chicken CXCLi2, among other cytokines and chemokines. The results from this study demonstrate that ILTV gG interferes with chemokine and cytokine transcription at different steps of the inflammatory cascade, thus altering inflammation, virulence, and the balance of the immune response to infection.IMPORTANCEInfectious laryngotracheitis virus is an alphaherpesvirus that expresses gG, a conserved broad-range viral chemokine-binding protein known to interfere with host immune responses. However, little is known about how gG modifies virulence and influences the inflammatory signaling cascade associated with infection. Here, data fromin vitroandin vivoinfection studies are presented. These data show that gG has a direct impact on the transcription of cytokines and chemokine ligandsin vitro(such as chicken CXCL8 orthologues, among others), which explains the altered balance of the inflammatory response that is associated with gG during ILTV infection of the upper respiratory tract of chickens. This is the first report to associate gG with the dysregulation of cytokine transcription at different stages of the inflammatory cascade triggered by ILTV infection of the natural host.

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Immune Responses in the Eye-Associated Lymphoid Tissues of Chickens after Ocular Inoculation with Vaccine and Virulent Strains of the Respiratory Infectious Laryngotracheitis Virus (ILTV)

Viruses ◽

10.3390/v11070635 ◽

2019 ◽

Vol 11 (7) ◽

pp. 635

Author(s):

Gabriela Beltrán ◽

David J. Hurley ◽

Robert M. Gogal ◽

Shayan Sharif ◽

Leah R. Read ◽

...

Keyword(s):

Immune Responses ◽

Virulent Strain ◽

Harderian Gland ◽

Lymphoid Tissues ◽

Specific Cell ◽

Infectious Laryngotracheitis Virus ◽

Viral Genomes ◽

Virulent Strains ◽

Infectious Laryngotracheitis ◽

Laryngotracheitis Virus

Infectious laryngotracheitis (ILT) is an acute respiratory disease of poultry caused by infectious laryngotracheitis virus (ILTV). Control of the disease with live attenuated vaccines administered via eye drop build upon immune responses generated by the eye-associated lymphoid tissues. The aim of this study was to assess cytokine and lymphocyte changes in the conjunctiva-associated lymphoid tissues (CALT) and Harderian gland (HG) stimulated by the ocular inoculation of the ILTV chicken embryo origin (CEO) vaccine strain and virulent strain 63140. This study offers strong evidence to support the roles that the CALT and HG play in the development of protective ILTV immune responses. It supports the premise that ILTV-mediated immunomodulation favors the B cell response over those of T cells. Further, it provides evidence that expansions of CD8α+ cells, with the concomitant expression of the Granzyme A gene, are key to reducing viral genomes in the CALT and halting ILTV cytolytic replication in the conjunctiva. Ultimately, this study revealed that the early upregulation of interleukin (IL)-12p40 and Interferon (IFN)-γ cytokine genes, which shape the antigen-specific cell-mediated immune responses, retarded the decline of virus replication, and enhanced the development of lesions in the conjunctiva epithelium.

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Immune responses to infectious laryngotracheitis virus

Developmental & Comparative Immunology ◽

10.1016/j.dci.2013.03.022 ◽

2013 ◽

Vol 41 (3) ◽

pp. 454-462 ◽

Cited By ~ 31

Author(s):

Mauricio J.C. Coppo ◽

Carol A. Hartley ◽

Joanne M. Devlin

Keyword(s):

Immune Responses ◽

Infectious Laryngotracheitis Virus ◽

Infectious Laryngotracheitis ◽

Laryngotracheitis Virus

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Immunoinformatics Approach for Multiepitopes Vaccine Prediction against Glycoprotein B of Avian Infectious Laryngotracheitis Virus

Advances in Bioinformatics ◽

10.1155/2019/1270485 ◽

2019 ◽

Vol 2019 ◽

pp. 1-23 ◽

Cited By ~ 7

Author(s):

Sumaia A. Ali ◽

Yassir A. Almofti ◽

Khoubieb A. Abd-elrahman

Keyword(s):

B Cell ◽

Glycoprotein B ◽

Economic Losses ◽

Upper Respiratory Tract ◽

Infectious Laryngotracheitis Virus ◽

B Cell Epitopes ◽

Mhc Ii ◽

High Affinity ◽

Infectious Laryngotracheitis ◽

Laryngotracheitis Virus

Infectious laryngotracheitis virus (ILTV) is a gallid herpesvirus type 1, a member of the genus Iltovirus. It causes an infection in the upper respiratory tract mainly trachea which results in significant economic losses in the poultry industry worldwide. Vaccination against ILTV produced latent infected carriers’ birds, which become a source of virus transmission to nonvaccinated flocks. Thus this study aimed to design safe multiepitopes vaccine against glycoprotein B of ILT virus using immunoinformatic tools. Forty-four sequences of complete envelope glycoprotein B were retrieved from GenBank of National Center for Biotechnology Information (NCBI) and aligned for conservancy by multiple sequence alignment (MSA). Immune Epitope Database (IEDB) analysis resources were used to predict and analyze candidate epitopes that could act as a promising peptide vaccine. For B cell epitopes, thirty-one linear epitopes were predicted using Bepipred. However eight epitopes were found to be on both surface and antigenic epitopes using Emini surface accessibility and antigenicity, respectively. Three epitopes (190KKLP193, 386YSSTHVRS393, and 317KESV320) were proposed as B cell epitopes. For T cells several epitopes were interacted with MHC class I with high affinity and specificity, but the best recognized epitopes were 118YVFNVTLYY126, 335VSYKNSYHF343, and 622YLLYEDYTF630. MHC-II binding epitopes, 301FLTDEQFTI309,277FLEIANYQV285, and 743IASFLSNPF751, were proposed as promising epitopes due to their high affinity for MHC-II molecules. Moreover the docked ligand epitopes from MHC-1 molecule exhibited high binding affinity with the receptors; BF chicken alleles (BF2 2101 and 0401) expressed by the lower global energy of the molecules. In this study nine epitopes were predicted as promising vaccine candidate against ILTV. In vivo and in vitro studies are required to support the effectiveness of these predicted epitopes as a multipeptide vaccine through clinical trials.

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Pathogenic and Transmission Potential of Wildtype and Chicken Embryo Origin (CEO) Vaccine Revertant Infectious Laryngotracheitis Virus

Viruses ◽

10.3390/v13040541 ◽

2021 ◽

Vol 13 (4) ◽

pp. 541

Author(s):

Ana Perez-Contreras ◽

Catalina Barboza-Solis ◽

Shahnas M. Najimudeen ◽

Sylvia Checkley ◽

Frank van der Meer ◽

...

Keyword(s):

Chicken Embryo ◽

Severe Disease ◽

Clinical Signs ◽

Upper Respiratory Tract ◽

Infectious Laryngotracheitis Virus ◽

Live Attenuated Vaccines ◽

Transmission Potential ◽

Infectious Laryngotracheitis ◽

Laryngotracheitis Virus ◽

Embryo Origin

Infectious laryngotracheitis (ILT) is an infectious upper respiratory tract disease that impacts the poultry industry worldwide. ILT is caused by an alphaherpesvirus commonly referred to as infectious laryngotracheitis virus (ILTV). Vaccination with live attenuated vaccines is practiced regularly for the control of ILT. However, extensive and improper use of live attenuated vaccines is related to vaccine viruses reverting to virulence. An increase in mortality and pathogenicity has been attributed to these vaccine revertant viruses. Recent studies characterized Canadian ILTV strains originating from ILT outbreaks as related to live attenuated vaccine virus revertants. However, information is scarce on the pathogenicity and transmission potential of these Canadian isolates. Hence, in this study, the pathogenicity and transmission potential of two wildtype ILTVs and a chicken embryo origin (CEO) vaccine revertant ILTV of Canadian origin were evaluated. To this end, 3-week-old specific pathogen-free chickens were experimentally infected with each of the ILTV isolates and compared to uninfected controls. Additionally, naïve chickens were exposed to the experimentally infected chickens to mimic naturally occurring infection. Pathogenicity of each of these ILTV isolates was evaluated by the severity of clinical signs, weight loss, mortality, and lesions observed at the necropsy. The transmission potential was evaluated by quantification of ILTV genome loads in oropharyngeal and cloacal swabs and tissue samples of the experimentally infected and contact-exposed chickens, as well as in the capacity to produce ILT in contact-exposed chickens. We observed that the CEO vaccine revertant ILTV isolate induced severe disease in comparison to the two wildtype ILTV isolates used in this study. According to ILTV genome load data, CEO vaccine revertant ILTV isolate was successfully transmitted to naïve contact-exposed chickens in comparison to the tested wildtype ILTV isolates. Overall, the Canadian origin CEO vaccine revertant ILTV isolate possesses higher virulence, and dissemination potential, when compared to the wildtype ILTV isolates used in this study. These findings have serious implications in ILT control in chickens.

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