Abstract
Parvoviruses are among the smallest of the DNA-containing viruses that infect a wide variety of vertebrates (Siegl et al. 1985). Two parvoviruses of human origin, the nonpathogenic adeno-associated virus 2 (AAV) and the parvovirus B19, a common human pathogen, have been studied extensively (Berns and Bohenzky 1987; Brown et al. 1994). AAV requires coinfection with a helper virus, such as adenovirus or herpesvirus, for its optimal replication (Berns 1990), but in the absence of a helper virus, the AAV genome establishes a latent infection in a site-specific manner (Kotin and Berns 1989; Kotin et al. 1990, 1991, 1992; Samulski et al. 1991). B19, by contrast, is an autonomously replicating virus with a remarkable tropism for human erythroid progenitor cells (Ozawa et al. 1986, 1987; Yaegashi et al. 1989; Srivastava and Lu 1988; Takahashi et al. 1990). We have described the construction of a recombinant AAV-B19 hybrid genome, in which we combined the remarkable features of these two parvoviruses, and speculated that such a hybrid vector may prove useful for high efficiency transduction of primary human hematopoietic progenitor cells (Srivastava et al. 1989). Indeed, it has become increasingly clear that the AAV-based vector system may prove to be a useful alternative to the more commonly used retroviral and adenoviral vectors for its potential use in human gene therapy (Muzyczka 1992; Carter 1993; Srivastava 1994). Despite these advances, a number of fundamental questions related to AAV remain unanswered. For example, the molecular details of viral assembly and the mechanism of viral entry into the host cell have not been rigorously analyzed. Furthermore, the feasibility of obtaining tissue-specific expression of an AAV-transduced gene has not been adequately addressed. Here, we provide experimental evidence to suggest that the vector assembly requires a precise signaling mechanism and that AAV infection of human cells is receptor-mediated. We also document erythroid lineage restricted expression following AAV-B19 hybrid vector-mediated transduction of primary human hematopoietic progenitor cells. Elucidation of the molecular details of these aspects of AAV biology will have important implications in the potential use of AAV as a vector in human gene therapy.
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Srivastava, A., Wang, XS., Ponnazhagan, S., Zhou, S.Z., Yoder, M.C. (1996). Adeno-associated Virus 2-Mediated Transduction and Erythroid Lineage-Specific Expression in Human Hematopoietic Progenitor Cells. In: Berns, K.I., Giraud, C. (eds) Adeno-Associated Virus (AAV) Vectors in Gene Therapy. Current Topics in Microbiology and Immunology, vol 218. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-80207-2_7
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DOI: https://doi.org/10.1007/978-3-642-80207-2_7
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