Nef alleles from children with non-progressive HIV-1 infection modulate MHC-II expression more efficiently than those from rapid progressors

Michael Schindler, Steffen Wildum, Nicoletta Casartelli, Margherita Doria, Frank Kirchhoff

Research output: Contribution to journalArticlepeer-review

Abstract

BACKGROUND: It has been established that defective nef genes and differences in the Nef-mediated downmodulation of CD4 and MHC-I cell surface expression can be associated with different rates of HIV-1 disease progression. OBJECTIVE: To evaluate whether nef alleles derived from perinatally HIV-1-infected children showing no, slow or rapid disease progression differ in their abilities to downmodulate mature MHC-II or to upregulate the invariant chain (Ii) associated with immature MHC-II complexes. METHODS: Nef alleles derived from HIV-1-infected children were cloned into expression vectors and proviral HIV-1 constructs co-expressing Nef and enhanced green fluorescence protein via an internal ribosomal entry site. Nef-mediated modulation of CD4, MHC-I, MHC-II or Ii surface expression was analysed by flow cytometric analysis of Jurkat T cells, monocytic THP-1 cells, CD4 T cells and macrophages transduced with vesicular stomatitis virus G-pseudotyped HIV-1 nef variants or transiently transfected HeLa class II transactivator cells. RESULTS: Nef alleles derived from HIV-1-infected children with non-progressive infection were significantly more active in the upregulation of Ii and downregulation of MHC-II than those derived from rapid progressors. CONCLUSION: Nef alleles particularly active in interfering with MHC-II antigen presentation are more frequently found in perinatally HIV-1-infected non-progressors than rapid progressors. Possibly in the context of an immature host immune system, strongly impaired MHC-II function might contribute to lower levels of immune activation and a decelerated loss of CD4 T cells.

Original languageEnglish
Pages (from-to)1103-1107
Number of pages5
JournalAIDS (London, England)
Volume21
Issue number9
DOIs
Publication statusPublished - May 2007

Keywords

  • HIV-1
  • Invariant chain
  • Major histocompatibility complex
  • Paediatric AIDS
  • T-cell activation

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy

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