Host restriction of lentiviruses and viral countermeasures: The Vif protein of maedi-visnavirus
BMC Seminar Thursday 24th of November at 12:00 in Læknagarður, room 343
Speaker: Dr. Stefán Ragnar Jónsson, Associate Researcher, Institute for Experimental Pathology at Keldur
Title: Host restriction of lentiviruses and viral countermeasures: The Vif protein of maedi-visnavirus
Abstract: Through evolution organisms have come up with multiple ways to evade lentiviral infections. Among these host defenses is the mammalian APOBEC3 (A3) family of cytidine deaminases that restricts infections by mutating viral DNA and impeding reverse transcription. To overcome this antiviral activity, most lentiviruses express a viral accessory protein called Vif, which mediates the ubiquitylation and subsequent proteasomal degradation of A3 proteins. Different lentiviral Vif proteins have evolved to employ the same canonical E3 ubiquitin ligase complexes, along with distinct non-canonical host cofactors for their activities. Unlike HIV-1 Vif and other primate lentiviral Vif proteins which recruit CBFβ as the noncanonical cofactor, non-primate lentiviral Vif proteins have developed different cofactor recruitment mechanisms. Maedi–visna virus (MVV) sequesters Cyclophilin A (CypA) as the noncanonical cofactor for the Vif-mediated ubiquitination of ovine A3 proteins. Since CBFβ and CypA are both highly conserved among mammals, the requirement for two different cellular cofactors suggests that these two A3-targeting Vif proteins have different biochemical and structural properties. We recently obtained a cryo-EM structure of MVV Vif in complex with ovine CypA and E3 ligase components. The structure along with our biochemical and functional analysis reveals conserved and unique structural elements of MVV Vif and its interactions with cognate cellular proteins, advancing our understanding of the mechanism of MVV Vif recruitment of cellular factors and the evolution of lentiviral Vif proteins.
Dr. Stefán Ragnar Jónsson, Associate Researcher, Institute for Experimental Pathology at Keldur.
Short bio: BS degree in biology from the University of Iceland, PhD degree in Biomedical Sciences from the University of Iceland under the supervision of Valgerður Andrésdóttir (Keldur) and Reuben S. Harris (University of Minnesota). Associate Researcher at the Institute for Experimental Pathology at Keldur since 2018.