The evolution of host range and receptor determinants for subgroup B feline leukemia viruses

• Main Author: Boomer, Sarah M
• Format: Dissertation
• Language: English
• Published: ProQuest Dissertations & Theses 01-01-1996
• Subjects: Microbiology; Molecular biology
• ISBN: 9780591247923; 0591247925

Retroviral evolution occurs by two means, mutation and recombination, and often results in changes in viral proteins. In particular, changes in the surface protein (SU) can alter the cell tropism and receptor recognition properties of the virus. Here, I examined the evolution of feline leukemia virus (FeLV) in vivo, demonstrating that subgroup A FeLV (FeLV-A-3281) recombined with endogenous FeLV during infection, giving rise to a novel subgroup B FeLV (FeLV-B-90Z). Where the FeLV-A infects primarily feline cells using an as yet unidentified receptor, FeLV-B-90Z infects several feline and non-feline cells and can use two known receptors, Pit1 and Pit2. Comparison of the recombination structure of FeLV-B-90Z with other FeLV-Bs demonstrated that all FeLV-B acquired the N-terminal half of the SU-encoding gene from enFeLV, although they differ in recombination junctions. This observation lead me to speculate that N-terminal substitutions affected the function of SU by altering receptor recognition properties. To test this hypothesis, I created viruses that contained SU-encoding genes that were chimeric between FeLV-A and FeLV-B and used them to infect various cell lines. Only a short region of the N-terminal SU, amino acids 78-125, harbors the primary determinant of host range in many non-feline cells and Pit1 receptor recognition. This region corresponds to a subdomain of the variable region A (VRA), the primary host range determinant of some murine leukemia viruses (MuLV). The presence of downstream FeLV-B sequences (VRB) enhanced infection in other non-feline cells and in cells expressing Pit2, suggesting that it was a secondary determinant. Finally, I examined the regions of Pit1 and Pit2 that were important for recognition by FeLV-B-like chimeras. The fourth extracellular domain of Pit molecules appeared to be a primary receptor determinant, although the presence of N-terminal receptor domains enhanced recognition by chimeras with FeLV-B only in the VRA. These data imply that the Pit1 fourth domain may interact with the VRA, and that N-terminal Pit domains act to stabilize, directly or indirectly, interactions with the VRB. Taken together, these data support the hypothesis that infection of new cell populations by viruses with altered receptor recognition determinants may drive evolution of FeLV-B viruses.