GASP and post endocytic trafficking of viral chemokine recep

A number of human and animal herpes (HHV4-8) and pox viruses encode G -protein coupled receptors (GPCRs) with seven transmembrane (7TM) segments - most of which are clearly related to human chemokine receptors. It appears, that these receptors are used by the virus for either immune evasion, cellular transformation, tissue targeting, and possibly for cell entry. In addition, many virally-encoded chemokine 7TM/GPCRs have been suggested to be causally involved in pathogenic phenotypes like Kaposi sarcoma, atherosclerosis and HIV- infection. However, to date, the role of these receptors during the viral life cycle and in viral pathogenesis is poorly understood. The majority of these receptors is found in the membranes of intracellular organelles that include components of the endocytotic pathway, i.e. multivesicular endosomes/lysosomes. It was suggested that this is the place where the viral receptors are incorporated into the viral membranes during the final stages virus assembly. Here, we set out to elucidate the mechanisms by which these viral receptors are endocytosed and targeted to these intracellular lysosomal compartments. One protein has recently been identified that specifically targets 7TM/GPCRs - typically by interaction with their carboxy-terminal domains - to the degradative pathways. This protein is the GPCR-associated sorting protein GASP. By addressing the post-endocytic trafficking properties of these viral receptors and their possible interaction with GASP, we hope to gain important insights in the function and pathology of these viral proteins.

A number of human and animal herpes (HHV4-8) and pox viruses encode G -protein coupled receptors (GPCRs) with seven transmembrane (7TM) segments - most of which are clearly related to human chemokine receptors. It appears, that these receptors are used by the virus for either immune evasion, cellular transformation, tissue targeting, and possibly for cell entry. In addition, many virally-encoded chemokine 7TM/GPCRs have been suggested to be causally involved in pathogenic phenotypes like Kaposi sarcoma, atherosclerosis and HIV- infection. However, to date, the role of these receptors during the viral life cycle and in viral pathogenesis is poorly understood. The majority of these receptors is found in the membranes of intracellular organelles that include components of the endocytotic pathway, i.e. multivesicular endosomes/lysosomes. It was suggested that this is the place where the viral receptors are incorporated into the viral membranes during the final stages virus assembly. Here, we set out to elucidate the mechanisms by which these viral receptors are endocytosed and targeted to these intracellular lysosomal compartments. One protein has recently been identified that specifically targets 7TM/GPCRs - typically by interaction with their carboxy-terminal domains - to the degradative pathways. This protein is the GPCR-associated sorting protein GASP. By addressing the post-endocytic trafficking properties of these viral receptors and their possible interaction with GASP, we hope to gain important insights in the function and pathology of these viral proteins.