Nef from primary isolates of human immunodeficiency virus type 1 suppresses surface CD4 expression in human and mouse T cells
| Autor: | D C Shugars, J V Garcia, R Swanstrom, S. J. Anderson |
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| Rok vydání: | 1993 |
| Předmět: |
Male
Genes Viral T-Lymphocytes viruses Molecular Sequence Data Immunology Biology Transfection medicine.disease_cause Polymerase Chain Reaction Microbiology Gene Products nef Virus Cell Line Mice Antigens CD Transcription (biology) Virology HIV Seropositivity medicine Animals Humans Amino Acid Sequence nef Gene Products Human Immunodeficiency Virus Cloning Molecular Gene HIV Long Terminal Repeat Acquired Immunodeficiency Syndrome Base Sequence Sequence Homology Amino Acid Chromosome Mapping virus diseases Simian immunodeficiency virus Flow Cytometry Long terminal repeat In vitro Genes nef Oligodeoxyribonucleotides Cell culture Insect Science CD4 Antigens HIV-1 Research Article |
| Zdroj: | Journal of Virology. 67:4923-4931 |
| ISSN: | 1098-5514 0022-538X |
| DOI: | 10.1128/jvi.67.8.4923-4931.1993 |
| Popis: | The human immunodeficiency virus type 1 (HIV-1) nef gene was originally described as a negative regulator of transcription from the viral long terminal repeat promoter. This observation has been disputed, and the function of Nef remains unclear. In vivo experiments have indicated that an intact nef gene is required for disease progression in macaques infected with simian immunodeficiency virus, suggesting a role for Nef in the pathogenesis of AIDS. We and others have previously shown that expression of Nef in cells bearing surface CD4 results in a sustained decrease in surface CD4 expression. This was demonstrated for Nef from two laboratory strains of HIV-1, Bru and SF2. Because both of these isolates were passaged in vitro prior to molecular cloning and in vitro passage can result in mutations which might alter nef gene function, we have analyzed two primary isolates of Nef for their ability to suppress cell surface CD4 expression. The nef genes of HIV-1 isolates from two patients with fewer than 200 CD4+ T cells per mm3 of blood were introduced into human and mouse T-cell lines by retrovirus-mediated gene transfer. Expression of Nef from both isolates correlated with a decrease in surface expression of both human and mouse CD4. To determine whether the ability to suppress surface CD4 expression is a general function of Nef, we also tested an artificially generated consensus nef gene derived from analysis of 54 patient isolates of HIV-1. Expression of the consensus Nef protein also correlated with decreased cell surface CD4 expression in both mouse and human T-cell lines. These results suggest that the ability to suppress cell surface CD4 expression is an intrinsic feature of HIV-1 Nef. |
| Databáze: | OpenAIRE |
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