Human parvovirus B19 causes a spectrum of clinical syndromes. Recently, the cell surface receptor for B19 on erythoid prgenitor cells was identified as the glycosphingolipid globoside of the P antigen blood system and the presence of globoside on a wide variety of tissue types may help explain the range of B19 tissue tropism and the variety of clinical syndromes caused by B19 infection. However, in experiments showing B19 binding to tissue extracted neutral glycosphingolipids on high performance thin layer chromatography plates, the investigator demonstrated B19 binding to more complex globo-series glycosphingolipids, and a neolacto-series glcosphingolipid, paragloboside, in addition to globoside. These results raised questions about the natures of the binding. Does B19 have two distinct carbohydrate binding domains, one specific for a globo-series motif and the second specifiic for a neolacto-series oligosaccharide with local conformation and charge distribution common to both globo-series and neolacto-series glycoshingolipoids capable of binding B19? As a first step in elucidation of the nature of B19 binding to its cell surface receptor, the investigator proposes to characterize the glycoshingolipid and viral structures involved in B19 binding.
The specific aims are: 1) to identify the structural determinants of glycoshingolipid receptors involved in B19 binding, 2) to identify the viral structures by which B19 binds to glycosphingolipid receptors, and 3) to determine the receptor number, density and binding behavior on cells permissive for B19 infection. The long term goal is a better understanding of the structure-function relationship between B19 and its cell surface receptor as it relates to pathogenesis, development of agents for viral prophylaxis, candidate B19 vaccines, and vectors for gene therapy.
| Cooling, Laura L W; Zhang, De Sheng; Naides, Stanley J et al. (2003) Glycosphingolipid expression in acute nonlymphocytic leukemia: common expression of shiga toxin and parvovirus B19 receptors on early myeloblasts. Blood 101:711-21 |
| Ray, N B; Nieva, D R; Seftor, E A et al. (2001) Induction of an invasive phenotype by human parvovirus B19 in normal human synovial fibroblasts. Arthritis Rheum 44:1582-6 |
