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

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.

• Authors: Michael Schindler, Steffen Wildum, Nicoletta Casartelli, Margherita Doria, Frank Kirchhoff
• Journal: AIDS (London, England) (AIDS) Vol. 21 Issue 9 Pg. 1103-7 (May 31 2007) ISSN: 0269-9370 [Print] England
• PMID: 17502720 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Antigens, Differentiation, B-Lymphocyte
• Antigens, Viral
• CD4 Antigens
• Histocompatibility Antigens Class I
• Histocompatibility Antigens Class II
• invariant chain

Topics

• Acquired Immunodeficiency Syndrome (genetics, immunology)
• Antigens, Differentiation, B-Lymphocyte (genetics)
• Antigens, Viral (genetics, immunology)
• CD4 Antigens (genetics)
• CD4-Positive T-Lymphocytes (immunology)
• Down-Regulation (genetics)
• Gene Expression Regulation, Viral (genetics)
• Genes, nef (genetics)
• HIV Infections (genetics, immunology)
• HIV Long-Term Survivors
• HIV-1 (genetics)
• HeLa Cells
• Histocompatibility Antigens Class I (genetics, immunology)
• Histocompatibility Antigens Class II (genetics, immunology)
• Humans
• Infant, Newborn
• Jurkat Cells
• Lymphocyte Activation (genetics)
• Up-Regulation (genetics)