By R. F. Doolittle, D. F. Feng, M. A. McClure, M. S. Johnson (auth.), Ronald Swanstrom Ph.D., Peter K. Vogt M.D. (eds.)

This ebook provides a synthesis of present wisdom on ret- rovirology. every one bankruptcy offers with a distinct step within the virus existence cycle, detailing the molecular elements of virus replication. The comparability of alternative retroviruses exemplifies diversifications. particular subject matters contain the evolution of retrovirus genomes, integration of the provirus, viral DNA transcriptional and translational regulate of viral gene expression, processing of viral proteins, and packaging of virion RNA. information on HIV and HTLV-1 are coated in addition to study on animal retrovirus sys- tems.

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Recent studies have shown that some of the unintegrated viral DNA molecules found in MLV-infected cells do indeed have this structure (FUJIWARA and MIZUUCHI 1988; BROWN et al. 1989). Integration of Retroviral DNA - 25 ............................ ACTTTA TT AT TCT TTCATTAT ............................ Preintegration ............................ TGAAATGGAAGTAGAGACAAGTAATA .................... • ...... ·target site U3 end AATGAAAG TTACTTTC ACTTTACCTTCATCTTGAAAG TGAAATGGAAGTAGAACTTTC -: + U5 end CTTTCATTj GAAAGTAA Unintegrated linear viral DNA CTTTCAATCTCTGTTCATTAT ...

1981; VARMUS 1983; BROWN et al. 1987). Even when integration events restricted by subsequent selection to a limited DNA region are examined, they are typically scattered at many sites in the region (HAYWARD et al. 1981; PAYNE et al. 1982; VAN OOYEN and NUSSE 1984; BROWN et al. 1987) (Fig. 6). However, there is considerable evidence that not all sites in the target genome are equally favored for integration in vivo. For example, integration sites are found near transcribed regions and DNaselhypersensitive sites at a frequency much greater than expected (VUA YAet al.

1986; ROHDEWOHLD et al. 1987), perhaps accounting for the observation that proviruses introduced into cells by natural integration are generally transcribed at a higher level than proviruses introduced by transfection (HWANG and GILBOA 1984). Moreover, integration of MLV into the HPRT gene in F9 mouse cells occurs about 100-fold less frequently than would be expected if there were no bias (KING et al. 1985). The best evidence for preferred integration sites is provided by the recent work of SHIH et al.

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