Tuyển tập các báo cáo nghiên cứu về y học được đăng trên tạp chí y học Respiratory Research cung cấp cho các bạn kiến thức về ngành y đề tài: Distinctive receptor binding properties of the surface glycoprotein of a natural Feline Leukemia Virus isolate with unusual disease spectrum. | Bolin et al. Retrovirology 2011 8 35 http content 8 1 35 RETROVIROLOGY RESEARCH Open Access Distinctive receptor binding properties of the surface glycoprotein of a natural Feline Leukemia Virus isolate with unusual disease spectrum Lisa L Bolin1 Chandtip Chandhasin1 3 Patricia A Lobelle-Rich1 Lorraine M Albritton2 and Laura S Levy1 Abstract Background Feline leukemia virus FeLV -945 a member of the FeLV-A subgroup was previously isolated from a cohort of naturally infected cats. An unusual multicentric lymphoma of non-T-cell origin was observed in natural and experimental infection with FeLV-945. Previous studies implicated the FeLV-945 surface glycoprotein SU as a determinant of disease outcome by an as yet unknown mechanism. The present studies demonstrate that FeLV-945 SU confers distinctive properties of binding to the cell surface receptor. Results Virions bearing the FeLV-945 Env protein were observed to bind the cell surface receptor with significantly increased efficiency as was soluble FeLV-945 SU protein as compared to the corresponding virions or soluble protein from a prototype FeLV-A isolate. SU proteins cloned from other cohort isolates exhibited increased binding efficiency comparable to or greater than FeLV-945 SU. Mutational analysis implicated a domain containing variable region B VRB to be the major determinant of increased receptor binding and identified a single residue valine 186 to be responsible for the effect. Conclusions The FeLV-945 SU protein binds its cell surface receptor feTHTR1 with significantly greater efficiency than does that of prototype FeLV-A FeLV-A 61E when present on the surface of virus particles or in soluble form demonstrating a 2-fold difference in the relative dissociation constant. The results implicate a single residue valine 186 as the major determinant of increased binding affinity. Computational modeling suggests a molecular mechanism by which residue 186 interacts with the receptor-binding .
