VIRUSES AND HEMATOPOEIESIS

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Studies of the interaction of hematopoietic cells and viruses have concentrated on interesting members of the Parvoviridae and Flaviviridae families. 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 acute and fulminant hepatitis syndromes, 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 another member of the Erythrovirus genus that infects pig-tailed 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 viral studies include cloning and sequencing of a member of the adeno-associated virus genus (AAV), the tissue tropism of which differs from the conventional AAV-2; further experiments to determine the nature of the cell surface receptor for AAV-2; and functional analysis of the non-structural protein of B19 parvovirus, which is responsible for viral cell killing. Of the Flaviviridae, hepatitis G or GBV-C, a novel member of the flavi-pestivirus group, has been detected by gene amplification in a large number of normal individuals: approximately 6% of normal Vietnamese are viremic and more recent studies of children in the Washington area show that 9% of plasma samples contain GBV-C sequences. Genetic heterogeneity is high among all isolates sequenced to date. Whether GBV-C represents a true hepatitis virus, 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 questions.