Properties, Functions, and Drug Targeting of the Multifunctional Nucleocapsid Protein of the Human Immunodeficiency Virus

Properties and functions of the nucleocapsid protein in virus assembly

“…These two main components of NC chaperoning activity are also found in other retroviral NC proteins from gamma and alpharetroviruses, 16,17,47,49,50 in the flaviviridae core proteins 58 and in cellular proteins such as p50, FMRP and PrP. 59 In conclusion, the dynamic interplay of the NC hydrophobic platform and basic domains with the viral nucleic acids via the binding, fraying, condensing and annealing properties of NC may well account for its essential functions in virus replication (Fig.…”

“…58 The second NC chaperoning component consists in NC-directed annealing of two NAs with complementary sequences when present in the same complex, namely TAR and cTAR sequences. 16,18,40 This is illustrated by the rapid annealing of the complementary TAR sequences which appears to require both the fraying and annealing elements of NC, the latter relying on the numerous NC basic residues which neutralize the phosphates of the NA backbone and in turn contribute to the molecular crowding effect.…”

“…Importantly, mutating either one or more of the CCHC residues, that modify the globular folding and prevent formation of the NC hydrophobic plateau, modifies Gag trafficking in the producer cell, alters the virion core structure and causes a complete loss of virus infectivity. 15,16,18,[33][34][35][36][37][38][39][40] Nucleic acid binding, condensing and chaperoning properties of NC protein. NC protein binds with high affinity to a very large panel of NA sequences, including in the form of small synthetic ODN (reviewed in refs.…”

“…42,43 Regarding binding specificity, NC in the form of the Gag polyprotein precursor appears to specifically recognize the Psi encapsidation sequences, which is thought to account for the selection of the genomic RNA among a vast excess of cellular RNAs, during the initial stage of particle assembly (reviewed in refs. 16,[44][45][46].…”

“…In fact, NC is part of the Gag precursor, which, in the form of GagΔp6, appears to tightly and stably bind the genomic RNA, preferably the Psi packaging sequences, and exhibits chaperoning activity in vitro and in assembling virions. 16 NC preference for the viral packaging sequences may account for the genomic RNA selection in the assembly process and the particle assembly itself, but when and where Gag-NC operates is still a matter of debate. Selection could take place soon after Gag translation of the genome length RNA by the ribosome machinery, which would then occur on translating polysomes in a cis-dependent manner and could involve a folding switch of the genomic leader region encompassing the packaging sequences and the internal ribosome entry segment.…”