Marek's disease virus-encoded vIL-8 gene is involved in early cytolytic infection but dispensable for establishment of latency.
Marek's disease, a lymphoproliferative disease of chickens, is caused by an alphaherpesvirus, Marek's disease virus (MDV). This virus encodes a virokine, vIL-8, with general homology to cellular CXC chemokines such as interleukin-8 (IL-8) and Gro-alpha. To study the function of vIL-8 gene, we deleted both copies of vIL-8 residing in the terminal repeat long and internal repeat long region of the viral genome and generated a mutant virus with vIL-8 deleted, rMd5/DeltavIL-8. Growth kinetics study showed that vIL-8 gene is dispensable for virus replication in cell culture. In vivo, the vIL-8 gene is involved in early cytolytic infections in lymphoid organs, as evidenced by limited viral antigen expression of rMd5/DeltavIL-8. However, the rMd5/DeltavIL-8 virus is unimpaired in virus replication in the feather follicle epithelium. vIL-8 does not appear to be important for establishment of latency, since rMd5/DeltavIL-8 and the wild-type virus have similar viremia titers at 14 days postinfection, a period when the virus titer comes primarily from reactivated latent genomes. Nevertheless, because of the impaired cytolytic infections, the overall transformation efficiency of the virus with vIL-8 deleted is much lower, as reflected by the reduced number of transformed cells at 5 weeks postinoculation and the presence of fewer gross tumors. Importantly, the revertant virus that restored the expression of vIL-8 gene also restored the wild-type phenotype, indicating the deficient phenotypes are results of vIL-8 deletion. One of the interesting differences between the MDV vIL-8 gene and its cellular counterpart is the presence of a DKR (Asp-Lys-Arg) motif instead of ELR (Glu-Leu-Arg) preceding the invariable CXC motif. To study the significance of this variation, we generated recombinant MDV, rMd5/vIL-8-ELR, carrying the ELR motif. Both in vitro and in vivo studies revealed that the DKR motif is as competent as ELR in pathogenesis of MDV.
Cui
Xiaoping
X
Pathobiology and Diagnostic Investigation, College of Veterinary Medicine, Michigan State University, East Lansing, Michigan 48824, USA.
Lee
Lucy F
LF
Reed
Willie M
WM
Kung
Hsing-Jien
HJ
Reddy
Sanjay M
SM
D000818:Animals; D002645:Chickens; D005260:Female; D017353:Gene Deletion; D008381:Herpesvirus 2, Gallid / Q000235:genetics / Q000472:pathogenicity* / Q000502:physiology; D016209:Interleukin-8 / Q000235:genetics* / Q000378:metabolism; D008221:Lymphoid Tissue / Q000473:pathology / Q000821:virology; D008297:Male; D008380:Marek Disease / Q000503:physiopathology / Q000821:virology*; D011201:Poultry Diseases / Q000503:physiopathology / Q000821:virology; D011995:Recombination, Genetic; D014764:Viral Proteins / Q000235:genetics* / Q000378:metabolism; D017735:Virus Latency; D014779:Virus Replication
D016209:Interleukin-8; D014764:Viral Proteins