Retroviruses are enveloped plus-strand RNA viruses that can cause cancer, immunodeficiency and neurological disorder in human and animals. Retroviruses have several unique properties, such as a genomic RNA in a dimeric form found in the virus, and a replication strategy called ‘copy-and-paste' during which the plus-strand genomic RNA is converted into a double-stranded DNA, subsequently integrated into the cellular genome. Two essential viral enzymes, reverse transcriptase (RT) and integrase (IN), direct this ‘copy-and-paste' replication. RT copies the genomic RNA generating the double-stranded proviral DNA, while IN catalyzes proviral DNA integration into the cellular DNA, then called the provirus. In that context, a major component of the virion core, the nucleocapsid protein (NC), was found to be a potent nucleic-acid chaperone that assists RT during the conversion of the genomic RNA into proviral DNA. Here we briefly review the interplay of NC with viral nucleic-acids, which enables rapid and faithful folding and hybridization of complementary sequences, and with active RT thus providing assistance to the synthesis of the complete proviral DNA. Because of its multiple roles in retrovirus replication, NC could be viewed as a two-faced Janus-chaperone acting on viral nucleic-acids and enzymes.

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