Analysis of the retrovirus capsid interdomain linker region

Brian Arvidson, Joshua Seeds, Mike Webb, Liam Finlay, Eric Barklis

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

In structural studies, the retrovirus capsid interdomain linker region has been shown as a flexible connector between the CA N-terminal domain and its C-terminal domain. To analyze the function of the linker region, we have examined the effects of three Moloney murine leukemia virus (M-MuLV) capsid linker mutations/variations in vivo, in the context of the full-length M-MuLV structural precursor protein (PrGag). Two mutations, A1SP and A5SP, respectively, inserted three and seven additional codons within the linker region to test the effects of increased linker lengths. The third variant, HIV/Mo, represented a chimeric HIV-1/M-MuLV PrGag protein, fused at the linker region. When expressed in cells, the three variants reduced the efficiency of virus particle assembly, with PrGag proteins and particles accumulating at the cellular plasma membranes. Although PrGag recognition of viral RNA was not impaired, the capsid linker variant particles were abnormal, with decreased stabilities, anomalous densities, and aberrant multiple lobed and tubular morphologies. Additionally, rather than crosslinking as PrGag dimers, particle-associated A1SP, A5SP, and HIV/Mo proteins showed an increased propensity to crosslink as trimers. Our results suggest that a wild-type retrovirus capsid linker region is required for the proper alignment of capsid protein domains.

Original languageEnglish (US)
Pages (from-to)166-177
Number of pages12
JournalVirology
Volume308
Issue number1
DOIs
StatePublished - Mar 30 2003

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Capsid
Retroviridae
Moloney murine leukemia virus
Human Immunodeficiency Virus Proteins
Viral Structural Proteins
Virus Assembly
Mutation
Viral RNA
Capsid Proteins
Codon
Virion
HIV-1
Proteins
Cell Membrane
HIV

ASJC Scopus subject areas

  • Virology
  • Infectious Diseases

Cite this

Analysis of the retrovirus capsid interdomain linker region. / Arvidson, Brian; Seeds, Joshua; Webb, Mike; Finlay, Liam; Barklis, Eric.

In: Virology, Vol. 308, No. 1, 30.03.2003, p. 166-177.

Research output: Contribution to journalArticle

Arvidson, B, Seeds, J, Webb, M, Finlay, L & Barklis, E 2003, 'Analysis of the retrovirus capsid interdomain linker region', Virology, vol. 308, no. 1, pp. 166-177. https://doi.org/10.1016/S0042-6822(02)00142-3
Arvidson, Brian ; Seeds, Joshua ; Webb, Mike ; Finlay, Liam ; Barklis, Eric. / Analysis of the retrovirus capsid interdomain linker region. In: Virology. 2003 ; Vol. 308, No. 1. pp. 166-177.
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