Retrospective on the all-in-one retroviral nucleocapsid protein

Highlights

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  This retrospective reviews 30 years of research on the retroviral nucleocapsid protein (NC) focusing on HIV-1 NC.

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  Originally considered as a non-specific nucleic-acid binding protein, NC has seminal functions in virus replication.

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  Indeed NC turns out to be a all-in-one viral protein that chaperones viral DNA synthesis and integration, and virus formation.

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  As a chaperone NC provides assistance to genetic recombination thus allowing the virus to escape the immune response and antiretroviral therapies against HIV-1.

Abstract

This review aims at briefly presenting a retrospect on the retroviral nucleocapsid protein (NC), from an unspecific nucleic acid binding protein (NABP) to an all-in-one viral protein with multiple key functions in the early and late phases of the retrovirus replication cycle, notably reverse transcription of the genomic RNA and viral DNA integration into the host genome, and selection of the genomic RNA together with the initial steps of virus morphogenesis. In this context we will discuss the notion that NC protein has a flexible conformation and is thus a member of the growing family of intrinsically disordered proteins (IDPs) where disorder may account, at least in part, for its function as a nucleic acid (NA) chaperone and possibly as a protein chaperone vis-à-vis the viral DNA polymerase during reverse transcription. Lastly, we will briefly review the development of new anti-retroviral/AIDS compounds targeting HIV-1 NC because it represents an ideal target due to its multiple roles in the early and late phases of virus replication and its high degree of conservation.