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Import of Retroviral Genomes

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Fusion of the viral membranes of most retroviruses with the plasma membrane releases the viral core into the cytoplasm. The retroviral core consists of the viral RNA genome, coated with NC protein, and the enzymes reverse transcriptase (RT) and integrase (IN), enclosed in a shell comprising the capsid (CA) protein. The RNA is reverse transcribed into DNA, which has to reach the nucleus in order to integrate and replicate as part of the host genome (see Chapter 7). The capsid core surrounding the viral RNA allows nucleotides necessary for reverse transcription to enter, but not larger molecules. It is thought that this core has to at least partially disassemble for DNA synthesis to continue but does not completely dissociate from the preintegration complex, comprising the viral DNA, IN, and other proteins. The mechanism of nuclear import of the preintegration complex is poorly understood, but it is quite clear that this structure is too large to pass through the nuclear pore complex. The betaretrovirus Moloney murine leukemia virus can efficiently infect only dividing cells when the nuclear membrane breaks down during mitosis. The viral preintegration complex has to then be tethered to chromatin so that it remains associated with cellular DNA when the nuclear membrane re-forms in daughter cells, circum-venting the need for active transport.

Principles of Virology

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