Molecular characterization of woodchuck type I interferons and their expression by woodchuck peripheral blood lymphocytes.
Interferon (IFN)-alpha and -beta are important antiviral mediators. IFN-alpha is widely used for the treatment of chronic hepatitis B. In our previous studies, a subtype of woodchuck IFN-alpha (wIFN-alpha) was characterized and has been shown to be active in suppressing the replication of woodchuck hepatitis virus (WHV) in vitro and vivo. Here, we refined the analysis of the IFN-alpha/beta system of the woodchuck and studied the expression of wIFN-alpha/beta in peripheral blood lymphocytes (PBLs) from naïve and WHV-infected woodchucks. A number of wIFN-alpha genes were sequenced and could be classified into 10 subtypes and 3 pseudotypes. The biological activity of different subtypes of wIFN-alpha was demonstrated by their ability to protect woodchuck cells against encephalomyocarditis virus infection and to induce MxA expression in woodchuck cells. Additionally, a partial sequence of wIFN-beta was characterized. A subtyping method for wIFN-alpha based on restriction length polymorphism analysis was developed. Further, the expression of wIFN by woodchuck PBLs after stimulation with polyI/C was investigated. The maximal production of wIFN by woodchuck PBLs occurred within the first 48 h after addition poly I/C. The wIFN-alpha subtypes 1, 4, and 5 were found to be produced by poly I/C-stimulated woodchuck PBLs, indicating a selective expression of wIFN-alpha subtypes. PBLs from chronically WHV-infected woodchucks showed a reduced ability to produce wIFN when stimulated with poly I/C. The results suggest that woodchucks with chronic WHV infection have impaired immunological responses to poly I/C.
Lu
Yinping
Y
Institut für Virologie, Universitätsklinikum Essen, Hufeland str. 55, 45122 Essen, Germany.
Xu
Yang
Y
Yang
Dongliang
D
Kemper
Thekla
T
Roggendorf
Michael
M
Lu
Mengji
M
D000818:Animals; D002478:Cells, Cultured; D017919:Hepatitis B Virus, Woodchuck / Q000187:drug effects; D007370:Interferon Type I / Q000096:biosynthesis / Q000097:blood*; D008214:Lymphocytes / Q000187:drug effects / Q000378:metabolism; D008392:Marmota / Q000097:blood*; D051379:Mice; D011070:Poly I-C / Q000494:pharmacology; D015183:Restriction Mapping; D016415:Sequence Alignment
D007370:Interferon Type I; D011070:Poly I-C