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

Infectious 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 vitro infection studies using tracheal organ tissue specimen cultures and blood-derived monocytes and in vivo infection 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.IMPORTANCE Infectious 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 from in vitro and in vivo infection studies are presented. These data show that gG has a direct impact on the transcription of cytokines and chemokine ligands in 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.

Identification of transcripts and protein products of the UL31, UL37, UL46, UL47, UL48, UL49 and US4 gene homologues of avian infectious laryngotracheitis virus.

In the present study, the transcription and protein expression of seven genes of infectious laryngotracheitis virus (ILTV) were investigated: UL31 and UL37 possess homologues in all known avian and mammalian herpesviruses, whereas UL46-UL49 and US4 are only conserved in most alphaherpesviruses. A peculiarity of the ILTV genome is the translocation of UL47 from the unique long region to a position upstream of US4 within the unique short region. Northern blot analyses revealed that all of the analysed genes were transcribed most abundantly during the late (gamma) phase of replication, but the only true late (gamma2) gene was UL47. Using monospecific rabbit antisera, the protein products of all of the genes could be detected and localized in ILTV-infected cells. Considerable amounts of the UL31, UL47 and UL48 gene products were found in the cell nuclei, whereas the other proteins were restricted largely to the cytoplasm. Like the respective tegument proteins of other herpesviruses, the UL37 and UL46-UL49 gene products of ILTV were incorporated into virus particles, whereas the UL31 protein and the glycoprotein encoded by US4 (gG) were not detectable in purified virions. It was also demonstrated that the UL48 protein of ILTV is able to activate an alphaherpesvirus immediate-early gene promoter, which is also a typical feature of other UL48 homologues. Taken together, these results indicate that the functions of all of the investigated ILTV proteins are related to those of their homologues in other alphaherpesviruses.

[The intermolecular disulfide bonds of the surface polypeptides in the infectious laryngotracheitis virus of hens]. / Mezhmolekuliarnye disul'fidnye sviazi poverkhnostnykh polipeptidov virusa infektsionnogo laringotrakheita kur.

The envelope proteins of chicken infectious laryngotracheitis virus were investigated using immunoblotting, radioimmuno-precipitation, and diagonal SDS-PAGE. Polypeptides with molecular weights of 205, 155, 115, 90, and 60 kDa were detected by rabbit antiserum and those of 205, 115, 90, and 60 kDa by chicken antiserum. When chicken antiserum was used, the 60 kDa polypeptide appeared to be the major immunogen. The 60 kDa polypeptide was shown to be a disulfide linked dimer with a molecular weight of 112 kDa. It is suggested that 60 kDa polypeptide is present in virions both in dimer (112 kDa) and monomer (60 kDa) forms.