These full-length transcripts (see Fig. 1) are packaged into viral particles at the membrane of the cell, following recruitment of the proteins synthesized earlier in the cycle. Packaging of the genomic transcripts into virion particles requires an RNA signal known as the Y sequence that lies 3’ of the 5’ LTR (8,s) and,therefore, downstream of the splicedonor site. This ensures that any spliced messages from the viral genome will not include the Y site and, so, will not be packaged. Hence, only full-length genomic transcripts become packaged into virions. If any vector DNA is to be recognized as a retroviral genome, this region must be included. Further definition of the Y sequence has shown that higher-titer packaging of genomes is possible by inclusion of a small region of the guggene (from bases 215 to 1039 in the MLV genome, as
numbered in ref. 10). This revised Y+ packaging sequence is included in the most recent generation of high-titer retroviral vectors (11) (see below). A viral protease encoded in the $01 region cleaves the envelope polyproteins into smaller components, and virus particles “bud ofF from the cell surface to
continue the next cycle of infection (for review, see ref. 12).
Thursday, August 19, 2010
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