Abstract
The formation of immature lentiviral particles is dependent on the multimerization of the Gag polyprotein at the plasma membrane of the infected cells. One key player in the virus assembly process is the capsid (CA) domain of Gag, which establishes the protein-protein interactions that give rise to the hexagonal lattice of Gag molecules in the immature virion. To gain a better understanding of the functional equivalence between the CA proteins of simian and feline immunodeficiency viruses (SIV and FIV, respectively), we generated a series of chimeric FIV Gag proteins in which the CA-coding region was partially or totally replaced by its SIV counterpart. All the FIV Gag chimeras were found to be assembly-defective; however, all of them are able to interact with wild-type SIV Gag and be recruited into extracellular virus-like particles, regardless of the SIV CA sequences present in the chimeric FIV Gag. The results presented here markedly contrast with our previous findings showing that chimeric SIVs carrying FIV CA-derived sequences are assembly-competent. Overall, our data support the notion that although the SIV and FIV CA proteins share 51% amino acid sequence similarity and exhibit a similar organization, i.e., an N-terminal domain joined by a flexible linker to a C-terminal domain, their functional exchange between these different lentiviruses is strictly dependent on the context of the recipient Gag precursor.
Highlights
Lentiviral assembly at the plasma membrane of the infected cells results from the multimerization of the Gag polyprotein into particles that bud into the extracellular medium
We showed that chimeric SIVs in which either the FIV CA-CTD alone, or the FIV CA-p1 region along with the first nine residues of FIV NC are substituted for the equivalent region of SIVSMM-PBj assemble into virions that incorporate the Env glycoprotein, package wild-type levels of viral genomic RNA and contain a functional reverse transcriptase; yet these chimeric SIVs are non-infectious due to a defect at a post-entry step [52]
The FIV gagSIVCA-SP1-NC(1–8) gene was generated to evaluate whether the SIV module comprising the entire CA domain and the C-terminally adjacent sequences extending from SP1 up to the amino acid residue 8 of NC are able to drive virus-like particles (VLPs) assembly in the context of the remaining FIV Gag domains
Summary
Lentiviral assembly at the plasma membrane of the infected cells results from the multimerization of the Gag polyprotein into particles that bud into the extracellular medium (reviewed in refs. [1,2]). FIV gag precursors carrying SIV capsid-derived sequences membrane [4,5,6,7,8,9] and is involved in the packaging of the SIV and human immunodeficiency virus type 1 (HIV-1) envelope (Env) glycoproteins into virions [3,10,11,12,13]; the central CA-SP1 domain establishes the Gag-Gag interactions that result in the hexagonal lattice of the spherical immature virion [14,15,16,17,18,19,20]; and the NC domain, through its two zinc finger motifs, selectively encapsidates the viral genomic RNA, which provides a nucleation scaffold for Gag assembly [21,22,23,24,25,26,27] Both SIV and FIV Gag C-terminal domains interact with components of the endosomal-sorting complexes required for transport (ESCRT), thereby promoting the release of virus particles from the plasma membrane of infected cells [26,28,29,30]. As a domain of the Gag precursor, the CA mediates the formation of the Gag lattice in the immature particle, whereas as an independent structural protein, it assembles into the fullerene core structure that distinguishes the mature infectious virion
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