RFBR Project “The role of Lymphocyte Phosphatase Associated Phosphoprotein in intracellular signaling upon B cell activation”
The phosphatase CD45 controls the phosphorylation level of a number of receptors and signaling molecules in lymphocytes and, thus, represents an essential regulator of lymphocyte activation. However, what molecules affect the activity of CD45 itself remains unknown. One of the possible regulators is a CD45-associated protein (CD45-AP). This transmembrane protein forms a supramolecular complex with CD45 as well as with the coreceptor CD4 and the kinase Lck. There is considerable evidence which allows to suggest that CD45-AP has an important but yet unrevealed cellular role.
The aim of the project is to identify the function of the CD45-AP protein. We assume that this aim can be attained by studying CD45-AP phosphorylation.
Based on the information regarding CD45-AP phospho-motifs, we will synthesize the corresponding phosphopeptides, conduct mice immunization, and obtain antibodies against phosphosites. Phospho-site specific antibodies will greatly facilitate future research and enable studying the role of CD45-AP in particular autoimmune and oncological diseases.
RSF Project “Searching new HIV-1 restriction factors affecting viral replication at cell-to-cell transmission settings”
HIV restriction factors are cellular proteins that inhibit viral replication at post-entry stage of virus life cycle. The dozens of cellular factors with antiviral activities have been described. However, only six main protein families, i.e. APOBEC, TRIM, Tetherin, SAMHD, and MX2, specifically restrict the replication of HIV. The mechanisms of restriction are specific for each factor, and affect different stages of viral replication that overall makes cells highly resistant to virus. Nevertheless, HIV has evolved its own proteins Vif, Vpr, Vpu, Vpx, Nef which efficiently counteract restriction factors and abolish their protective effects.
The role of restriction factors in HIV replication has been studied extensively upon infection with cell free virus. However, the transmission of HIV via cell-to-cell contacts has been demonstrated to play a pivotal role in virus dissemination in vivo. Hence, the examination of restriction factors in HIV replication under viral synapse formation may reveal the different effects of known factors or discover new restriction factors involved in the protection against HIV cell-to-cell transmission. We propose that viral synapse formed between infected and target cells induces a cell signaling in targets resulting in the expression of some restriction factors, which can be different from that induced by virus-cell fusion. The aim of this project is to determine restriction factors that enhance the resistance of cells to HIV-1 at cell-to-cell transmission settings.