Single Nef Proteins from HIV Type 1 Subtypes C and F Fail to Upregulate Invariant Chain Cell Surface Expression But Are Active for Other Functions
| Autor: | Horacio Salomón, Gabriela Turk, Michael Schindler, Mauricio Carobene, Philippe Benaroch, Swantje Gundlach |
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| Rok vydání: | 2009 |
| Předmět: |
Genotype
viruses CD3 Molecular Sequence Data Immunology Major histocompatibility complex Jurkat cells Jurkat Cells Downregulation and upregulation Virology Humans Amino Acid Sequence nef Gene Products Human Immunodeficiency Virus Receptors Immunologic Cells Cultured Phylogeny Regulation of gene expression biology Histocompatibility Antigens Class II virus diseases CD28 Transfection Cell biology Antigens Differentiation B-Lymphocyte Infectious Diseases Gene Expression Regulation HIV-1 Leukocytes Mononuclear biology.protein Signal transduction Sequence Alignment HeLa Cells |
| Zdroj: | AIDS Research and Human Retroviruses. 25:285-296 |
| ISSN: | 1931-8405 0889-2229 |
| Popis: | HIV-1 Nef protein plays a major role in viral immunopathogenesis, modulating surface expression of several immune receptors, altering signal transduction pathways, and enhancing viral infectivity, among other activities. Nef also exhibits great intersubtype diversity, but most studies have been focused only on Nef proteins from subtype B. Thus, little is known about the functional capacities of nonsubtype B Nef proteins in host cells. Here, we investigated cell surface regulation of MHC-I, MHC-II, the MHC-II-associated chaperone invariant chain (Ii), CD4, CD3, and CD28 in cells transfected or infected with five different Nef alleles including one HIV-1 subtype C and F allele. No significant difference among the Nef proteins regarding CD3, CD28, and MHC-II downregulation was observed. The NefC showed a slightly, yet significant, diminished capacity to downregulate MHC-I in all cells, as well as to downregulate CD4 in Jurkat cells and PBMCs. Strikingly, the two alleles from NefC and NefF were unable to upregulate the Ii chain both in transfected and infected cells. Moreover, the internalization rate of the surface Ii chain was only slightly affected by NefC and NefF, whereas it was drastically reduced by NefB. Nef domains known to be involved in Ii chain upregulation were conserved among the five alleles analyzed here. In summary, we identified two primary HIV-1 NefC and NefF alleles that are selectively impaired for Ii upregulation and that may help to elucidate the mechanism of this Nef function in the future. It will be important to determine whether the observed differences are HIV-1 subtype dependent and influence viral immunopathogenesis. |
| Databáze: | OpenAIRE |
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