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 hepatitis, we have analyzed using the polymerase chain reaction a large number of liver samples: in our experience, approximately 30% of liver tissue contain detectable B19 parvovirus, regardless of the primary diagnosis. These results suggest that the virus may persist in small amounts in visceral tissue without medical consequence. We have also discovered and characterized two new members of the Erythrovirus genus that infect pig-tailed macaque and rhesus macaque monkeys. This and other Erythroviruses share genetic homology and functional characteristics with B19 parvovirus. One member of the genus, simian parvovirus, may offer an animal model for human disease, as hydrops fatalis has been reproduced by experimental uterine inoculation during the mid-trimester of pregnancy. In vaccine trials, rhesus monkeys have been immunized with empty B19 parvovirus capsids that were formulated with several experimental adjuvants in order to elicit high titers of neutralizing antibodies. One such formulation should prove appropriate for a human vaccine to prevent parvovirus disease. 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, and the interactions of the structural and non-structural proteins with cellular proteins; and functional analysis of the non-structural protein of B19 parvovirus, which is responsible for viral cell killing. Our studies of putuative novel hepatitis viruses include the flavivirus, hepatitis G or GBV-C, an enterovirus A2, and a putative parvovirus or 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, but its tissue tropism, the nature of replication in the absence of a core protein, and the relationship of viral infection to disease remain important current areas of research. Currently TTV sequences are detected in 20% of American blood donors, and an increased number of children (~30%), but the high degree of sequence variation suggests that the current assay underestimates the true prevalence. The nature of the virus, and its tissue tropism and also active areas of research.
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