ESF-EMBO Symposium: Antiviral Applications of RNA Interference |
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Authors: | Olivier ter Brake Joost Haasnoot Jens Kurreck Ben Berkhout |
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Affiliation: | 1. Department of Microbiology and Myles H. Thaler Center for AIDS and Human Retrovirus Research, University of Virginia, 22908, Charlottesville, VA, USA 2. Department of Molecular Biology and Biochemistry, Center for Immunology and Center for Virus Research, University of California, 92697-3900, Irvine, CA, USA
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Abstract: | AIDS-associated, CCR5-tropic (R5) HIV-1 clones, isolated from a patient that never developed CXCR4-tropic HIV-1, replicate to a greater extent and cause greater cytopathic effects than R5 HIV-1 clones isolated before the onset of AIDS. Previously, we showed that HIV-1 Env substantially contributed to the enhanced replication of an AIDS clone. In order to determine if Nef makes a similar contribution, we cloned and phenotypically analyzed nef genes from a series of patient ACH142 derived R5 HIV-1 clones. The AIDS-associated Nef contains a series of residues found in Nef proteins from progressors [1]. In contrast to other reports [1–3], this AIDS-associated Nef downmodulated MHC-I to a greater extent and CD4 less than pre-AIDS Nef proteins. Additionally, all Nef proteins enhanced infectivity similarly in a single round of replication. Combined with our previous study, these data show that evolution of the HIV-1 env gene, but not the nef gene, within patient ACH142 significantly contributed to the enhanced replication and cytopathic effects of the AIDS-associated R5 HIV-1 clone. |
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