Studies of the interaction of hematopoietic cells and viruses have mainly concentrated on members of the Parvoviridae and with our interest in hepatitis-associated aplastic anemia, novel putative hepatitis agents. B19 parvovirus infects erythroid progenitor cells and infection in humans causes both the hematologic syndromes transient aplastic crisis and pure red cell aplasia as well as the common childhood exanthem fifth disease. Provoked by reports that B19 parvovirus might be involved in the etiology of rheumatoid arthritis, we have collaborated in studies using the polymerase chain reaction to analyze synovial tissues in patients with arthropathy: B19 DNA was detected in both rheumatoid and non-rheumatoid patients. As in our studies of B19 in hepatitis, these results suggest that the virus may persist in small amounts in tissues without medical consequence. Using a related simian Erythrovirus (SPV), may offer an animal model for human disease, and we have reproduced one of the medical consequences of B19 infection, hydrops fatalis, by experimental uterine inoculation during the mid-trimester of pregnancy. Other parvoviral studies include development of adeno-associated virus vectors based on a second human adeno-associated virus AAV-3, and comparative studies of the tissue tropism of with the conventional AAV-2; further experiments to determine early the early events of AAV infection, including the nature of the cell surface receptor for AAV-2.Our studies of putuative novel hepatitis viruses include the flavivirus, hepatitis G or GBV-C, an enterovirus A2, and a putative circovirus TTV. Hepatitis G/GBV-C RNA has been detected by gene amplification in a large number of normal individuals including children: serum samples from non-transfused children in the Washington area show that 9% of plasma samples contain GBV-C sequences, and with our recently developed antibody test, an additional13% have GBV-C specific antibody indicating previous infection. Testing of samples from hepatitis patients suggest that this virus is not associated with hepatitis, and that the virus does not replicate in hepatocytes. We have developed new PCR primers to detect the novel virus TTV, and with these assays we can detect TTV sequences in ~ 60% of American blood donors, but the high degree of sequence variation suggests that the current assay underestimates the true prevalence. In addition we have a method for in vitro culture of the virus, and are investigating the interaction of the virus with hematopoietic cells. Finally we have established a collaboration to study the role of the most recently identified putative hepatitis agent SEN-V. - Hepatitis; Aplastic anemia; Parvoviruses; Parvovirus B19; Adeno-associated virus; Novel hepatitis virus; Hepatitis G/GBV-C; TTV. - Human Subjects & Human Subjects: Interview, Questionaires, or Surveys Only
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