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.
Highlights
The nef gene of HIV-1 plays a pivotal role in the pathogenesis of AIDS [4,5,6,7,8]
We demonstrated that the ACH142 AIDS clone *E11 was better able to replicate and cause cytopathic effects in human fetal thymus-liver grafts implanted in severe combined immune deficient mice (SCID-hu thy/liv mice), than the pre-AIDS clones, 8G9 and 32D2 [60]
In order to determine if nef made a similar contribution, ACH142 nef genes were amplified from PHA-activated PBMC infected with the HIV-1 clones ACH142-*E11, 32D2, and 8G9
Summary
The nef gene of HIV-1 plays a pivotal role in the pathogenesis of AIDS [4,5,6,7,8]. For example, patients infected with nefdeleted HIV-1 exhibited much slower progression to AIDS [6,9,10,11]. We chose to focus on Nef's abilities to downmodulate CD4 [38] and cell surface MHC-I A and B molecules [39,40], and its ability to enhance viral infectivity [12,41,42]. These functions (page number not for citation purposes). When compared to non-progressor Nefs, progressor Nefs were better able to downmodulate CD4 and less able to downmodulate MHC-I molecules, and may have an increased ability to enhance HIV-1 infectivity [1,2]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
