Second-site compensatory mutations of HIV-1 capsid mutations

Colleen M. Noviello, Claudia S. López, Ben Kukull, Henry McNett, Amelia Still, Jacob Eccles, Rachel Sloan, Eric Barklis

Research output: Contribution to journalArticle

28 Scopus citations

Abstract

The human immunodeficiency virus (HIV) capsid (CA) protein assembles into a hexameric lattice that forms the mature virus core. Contacts between the CA N-terminal domain (NTD) of one monomer and the C-terminal domain (CTD) of the adjacent monomer are important for the assembly of this core. In this study, we have examined the effects of mutations in the NTD region associated with this interaction. We have found that such mutations yielded modest reductions of virus release but major effects on viral infectivity. Cell culture and in vitro assays indicate that the infectivity defects relate to abnormalities in the viral cores. We have selected second-site compensatory mutations that partially restored HIV infectivity. These mutations map to the CA CTD and to spacer peptide 1 (SP1), the portion of the precursor Gag protein immediately C terminal to the CTD. The compensatory mutations do not locate to the molecularly modeled intermolecular NTD-CTD interface. Rather, the compensatory mutations appear to act indirectly, possibly by realignment of the C-terminal helix of the CA CTD, which participates in the NTD-CTD interface and has been shown to serve an important role in the assembly of infectious virus.

Original languageEnglish (US)
Pages (from-to)4730-4738
Number of pages9
JournalJournal of virology
Volume85
Issue number10
DOIs
StatePublished - May 1 2011

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

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    Noviello, C. M., López, C. S., Kukull, B., McNett, H., Still, A., Eccles, J., Sloan, R., & Barklis, E. (2011). Second-site compensatory mutations of HIV-1 capsid mutations. Journal of virology, 85(10), 4730-4738. https://doi.org/10.1128/JVI.00099-11