Changes in HIV-1 capsid stability induced by common cytotoxic-TLymphocyte-driven viral sequence mutations

P. Schommers, G. Martrus, U. Matschl, M. Sirignano, M. Lutgehetmann, L. Richert, T. J. Hope, G. Fätkenheuer, Marcus Altfeld*

*Corresponding author for this work

Research output: Contribution to journalArticle

1 Scopus citations

Abstract

HIV-1-infected individuals with protective HLA class I alleles exhibit better control of viremia and slower disease progression. Virus control in these individuals has been associated with strong and potent HIV-1-specific cytotoxic-T-lymphocyte (CTL) responses restricted by protective HLA alleles, but control of viremia also occurs in the presence of selected CTL escape mutations. CTL escape mutations restricted by protective HLA class I molecules are frequently located in the conserved p24 Gag sequence of HIV-1 that encodes the conical capsid core and have been suggested to reduce viral replication capacity. In this study, the consequences of well-described CTL-associated p24 Gag sequence mutations for HIV-1 capsid stability were assessed using a cyclosporine (CsA) washout assay. The frequently occurring HLA-B57- and HLA-B27-associated CTL escape mutations T242N and R264K resulted in delayed capsid uncoating, suggesting modulation of capsid stability. The described compensatory mutations L268M and S173A observed in R264K viruses reconstituted the capsid-uncoating half-time. Interestingly, capsid stability was correlated with infectivity. Taken together, these data demonstrate that CTL-driven escape mutations within p24 Gag restricted by protective HLA class I alleles have a significant impact on capsid stability that might contribute to the persistent control of viral replication observed despite viral escape from CTL responses.

Original languageEnglish (US)
Pages (from-to)7579-7586
Number of pages8
JournalJournal of virology
Volume90
Issue number16
DOIs
StatePublished - 2016

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

Fingerprint Dive into the research topics of 'Changes in HIV-1 capsid stability induced by common cytotoxic-TLymphocyte-driven viral sequence mutations'. Together they form a unique fingerprint.

Cite this