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

2017 ◽  
Vol 92 (1) ◽  
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.

scholarly journals Glycoprotein G is a virulence factor in infectious laryngotracheitis virus

2006 ◽  
Vol 87 (10) ◽  
pp. 2839-2847 ◽  
Author(s):  
J. M. Devlin ◽  
G. F. Browning ◽  
C. A. Hartley ◽  
N. C. Kirkpatrick ◽  
A. Mahmoudian ◽  
...  
Keyword(s):  
Virulence Factor ◽  
Clinical Signs ◽  
Pcr Analysis ◽  
Infectious Laryngotracheitis Virus ◽  
Glycoprotein G ◽  
Infectious Laryngotracheitis ◽  
Laryngotracheitis Virus

Infectious laryngotracheitis virus (ILTV; Gallid herpesvirus 1) is an alphaherpesvirus that causes acute respiratory disease in chickens. The role of glycoprotein G (gG) in vitro has been investigated in a number of alphaherpesviruses, but the relevance of gG in vivo in the pathogenicity of ILTV or in other alphaherpesviruses is unknown. In this study, gG-deficient mutants of ILTV were generated and inoculated into specific-pathogen-free chickens to assess the role of gG in pathogenicity. In chickens, gG-deficient ILTV reached a similar titre to wild-type (wt) ILTV but was significantly attenuated with respect to induction of clinical signs, effect on weight gain and bird mortality. In addition, an increased tracheal mucosal thickness, reflecting increased inflammatory cell infiltration at the site of infection, was detected in birds inoculated with gG-deficient ILTV compared with birds inoculated with wt ILTV. The reinsertion of gG into gG-deficient ILTV restored the in vivo phenotype of the mutant to that of wt ILTV. Quantitative PCR analysis of the expression of the genes adjacent to gG demonstrated that they were not affected by the deletion of gG and investigations in vitro confirmed that the phenotype of gG-deficient ILTV was consistent with unaltered expression of these adjacent genes. This is the first reported study to demonstrate definitively that gG is a virulence factor in ILTV and that deletion of gG from this alphaherpesvirus genome causes marked attenuation of the virus in its natural host.

scholarly journals In vitro and in vivo characterization of glycoprotein C-deleted infectious laryngotracheitis virus

2009 ◽  
Vol 91 (4) ◽  
pp. 847-857 ◽  
Author(s):  
S. P. Pavlova ◽  
J. Veits ◽  
U. Blohm ◽  
C. Maresch ◽  
T. C. Mettenleiter ◽  
...  
Keyword(s):  
Infectious Laryngotracheitis Virus ◽  
Glycoprotein C ◽  
Infectious Laryngotracheitis ◽  
Laryngotracheitis Virus ◽  
In Vivo Characterization

scholarly journals 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

Vaccines ◽  
2021 ◽  
Vol 9 (8) ◽  
pp. 865
Author(s):  
Daniel Maekawa ◽  
Sylva M. Riblet ◽  
Patrick Whang ◽  
David J. Hurley ◽  
Maricarmen Garcia
Keyword(s):  
T Cells ◽  
Regulatory T Cells ◽  
Immune Responses ◽  
Nk Cells ◽  
Moderate Increase ◽  
Upper Respiratory Tract ◽  
Infectious Laryngotracheitis Virus ◽  
Vaccine Protection ◽  
Infectious Laryngotracheitis ◽  
Laryngotracheitis Virus

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.

scholarly journals Glycoprotein G (gG) production profile during infectious laryngotracheitis virus (ILTV) infection

PLoS ONE ◽  
2019 ◽  
Vol 14 (8) ◽  
pp. e0219475 ◽  
Author(s):  
Jorge Bendezu ◽  
Sandra Morales Ruiz ◽  
Ricardo Montesinos ◽  
Ricardo Choque Guevara ◽  
Aldo Rojas-Neyra ◽  
...  
Keyword(s):  
Infectious Laryngotracheitis Virus ◽  
Glycoprotein G ◽  
Infectious Laryngotracheitis ◽  
Laryngotracheitis Virus

scholarly journals In Vitro and In Vivo Relevance of Infectious Laryngotracheitis Virus gJ Proteins That Are Expressed from Spliced and Nonspliced mRNAs

2005 ◽  
Vol 79 (2) ◽  
pp. 705-716 ◽  
Author(s):  
Walter Fuchs ◽  
Dorothee Wiesner ◽  
Jutta Veits ◽  
Jens P. Teifke ◽  
Thomas C. Mettenleiter
Keyword(s):  
Severe Disease ◽  
Progeny Virus ◽  
Wild Type ◽  
Infectious Laryngotracheitis Virus ◽  
Live Virus ◽  
Specific Antibodies ◽  
Field Virus ◽  
Infectious Laryngotracheitis ◽  
Laryngotracheitis Virus

ABSTRACT The positional homologue in the infectious laryngotracheitis virus (ILTV) genome of the glycoprotein gJ gene of herpes simplex virus and the gp2 gene of equine herpesvirus 1 is expressed into four proteins of 85, 115, 160, and 200 kDa (J. Veits, B. Köllner, J. P. Teifke, H. Granzow, T. C. Mettenleiter, and W. Fuchs, Avian Dis. 47:330-342, 2003). RNA analyses revealed that these proteins are expressed from two different late (γ2) transcripts, an unspliced 5.5-kb and a spliced 4.3-kb mRNA that are translated into proteins of 985 and 611 amino acids, respectively. ILTV gJ is incorporated into virions and is modified by N- and O-linked glycosylation. After cotransfection of chicken cells with genomic DNA of a pathogenic ILTV strain and transfer plasmids, gJ-negative ILTV mutants could be isolated. In vitro growth studies demonstrated that deletion of the gJ gene has only minor effects on direct cell-to-cell spread as measured by plaque size. However, progeny virus titers of ILTV-ΔgJ were significantly reduced in comparison to those of the parental virus and a gJ rescue mutant. After experimental infection of chickens the gJ rescue mutant, like wild-type ILTV, caused severe disease and considerable mortality, whereas ILTV-ΔgJ was significantly attenuated. All immunized animals were protected against subsequent challenge infection with virulent ILTV. In sera collected after immunization with the gJ-rescue mutant or with wild-type ILTV, gJ-specific antibodies were detectable by immunofluorescence on cells that had been transfected with a gJ expression plasmid. As expected, no gJ-specific antibodies were found in sera obtained from chickens immunized with ILTV-ΔgJ. Thus, gJ deletion mutants of ILTV might be usable as attenuated live-virus vaccines. Furthermore, the gJ gene might constitute a reliable marker for serological discrimination between vaccinated and field virus-infected chickens.

scholarly journals Recombination of Globally Circulating Varicella-Zoster Virus

2015 ◽  
Vol 89 (14) ◽  
pp. 7133-7146 ◽  
Author(s):  
Peter Norberg ◽  
Daniel P. Depledge ◽  
Samit Kundu ◽  
Claire Atkinson ◽  
Julianne Brown ◽  
...  
Keyword(s):  
Varicella Zoster Virus ◽  
Genetic Recombination ◽  
Human Herpesvirus ◽  
Infectious Laryngotracheitis Virus ◽  
Live Attenuated Vaccine ◽  
Herpes Simplex Viruses ◽  
Varicella Zoster ◽  
Laryngotracheitis Virus

ABSTRACTVaricella-zoster virus (VZV) is a human herpesvirus, which during primary infection typically causes varicella (chicken pox) and establishes lifelong latency in sensory and autonomic ganglia. Later in life, the virus may reactivate to cause herpes zoster (HZ; also known as shingles). To prevent these diseases, a live-attenuated heterogeneous vaccine preparation, vOka, is used routinely in many countries worldwide. Recent studies of another alphaherpesvirus, infectious laryngotracheitis virus, demonstrate that live-attenuated vaccine strains can recombinein vivo, creating virulent progeny. These findings raised concerns about using attenuated herpesvirus vaccines under conditions that favor recombination. To investigate whether VZV may undergo recombination, which is a prerequisite for VZV vaccination to create such conditions, we here analyzed 115 complete VZV genomes. Our results demonstrate that recombination occurs frequently for VZV. It thus seems that VZV is fully capable of recombination if given the opportunity, which may have important implications for continued VZV vaccination. Although no interclade vaccine-wild-type recombinant strains were found, intraclade recombinants were frequently detected in clade 2, which harbors the vaccine strains, suggesting that the vaccine strains have already been involved in recombination events, eitherin vivoorin vitroduring passages in cell culture. Finally, previous partial and complete genomic studies have described strains that do not cluster phylogenetically to any of the five established clades. The additional VZV strains sequenced here, in combination with those previously published, have enabled us to formally define a novel sixth VZV clade.IMPORTANCEAlthough genetic recombination has been demonstrated to frequently occur for other human alphaherpesviruses, herpes simplex viruses 1 and 2, only a few ancient and isolated recent recombination events have hitherto been demonstrated for VZV. In the present study, we demonstrate that VZV also frequently undergoes genetic recombination, including strains belonging to the clade containing the vOKA strain.

scholarly journals The UL47 gene of avian infectious laryngotracheitis virus is not essential for in vitro replication but is relevant for virulence in chickens

2007 ◽  
Vol 88 (3) ◽  
pp. 732-742 ◽  
Author(s):  
Dorothee Helferich ◽  
Jutta Veits ◽  
Jens P. Teifke ◽  
Thomas C. Mettenleiter ◽  
Walter Fuchs
Keyword(s):  
Deletion Mutant ◽  
Cultured Cells ◽  
Functional Characterization ◽  
Wild Type Virus ◽  
Wild Type ◽  
Infectious Laryngotracheitis Virus ◽  
Live Virus ◽  
Infectious Laryngotracheitis ◽  
Laryngotracheitis Virus

The genome of infectious laryngotracheitis virus (ILTV) exhibits several differences from those of other avian and mammalian alphaherpesviruses. One of them is the translocation of the conserved UL47 gene from the unique long (UL) to the unique short (US) genome region, where UL47 is inserted upstream of the US4 gene homologue. As in other alphaherpesviruses, UL47 encodes a major tegument protein of ILTV particles, whereas the US4 gene product is a non-structural glycoprotein, gG, which is secreted from infected cells. For functional characterization, an ILTV recombinant was isolated in which US4 together with the 3′-terminal part of UL47 was replaced by a reporter gene cassette encoding green fluorescent protein. From this virus, UL47 and US4 single-gene deletion mutants without foreign sequences were derived and virus revertants were also generated. In vitro studies revealed that both genes were non-essential for ILTV replication in cultured cells. Whereas US4-negative ILTV exhibited no detectable growth defects, maximum virus titres of the double deletion mutant and of UL47-negative ILTV were reduced about 10-fold compared with those of wild-type virus and rescued virus. Experimental infection of chickens demonstrated that UL47-negative ILTV was significantly attenuated in vivo and was shed in reduced amounts, whereas wild-type and rescued viruses caused severe disease and high mortality rates. As all immunized animals were protected against subsequent challenge infection with virulent ILTV, the UL47 deletion mutant might be suitable as a live-virus vaccine.

Sign in / Sign up

Export Citation Format

Share Document