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Virology. 2011 Dec 20;421(2):253-65. doi: 10.1016/j.virol.2011.09.012. Epub 2011 Oct 26.

The interdomain linker region of HIV-1 capsid protein is a critical determinant of proper core assembly and stability.

Author information

  • 1Section on Viral Gene Regulation, Program in Genomics of Differentiation, Eunice Kennedy Shriver National Institute of Child Health, National Institutes of Health, Bethesda, MD 20892-2780, USA.

Abstract

The HIV-1 capsid protein consists of two independently folded domains connected by a flexible peptide linker (residues 146-150), the function of which remains to be defined. To investigate the role of this region in virus replication, we made alanine or leucine substitutions in each linker residue and two flanking residues. Three classes of mutants were identified: (i) S146A and T148A behave like wild type (WT); (ii) Y145A, I150A, and L151A are noninfectious, assemble unstable cores with aberrant morphology, and synthesize almost no viral DNA; and (iii) P147L and S149A display a poorly infectious, attenuated phenotype. Infectivity of P147L and S149A is rescued specifically by pseudotyping with vesicular stomatitis virus envelope glycoprotein. Moreover, despite having unstable cores, these mutants assemble WT-like structures and synthesize viral DNA, although less efficiently than WT. Collectively, these findings demonstrate that the linker region is essential for proper assembly and stability of cores and efficient replication.

Published by Elsevier Inc.

PMID:
22036671
[PubMed - indexed for MEDLINE]
PMCID:
PMC3573886
Free PMC Article

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