Short report

Nef does not contribute to replication differences between R5 pre-AIDS and AIDS HIV-1 clones from patient ACH142

Kevin C Olivieri¹ , Robert M Scoggins¹ , Brooks Broderick¹ , Maria LC Powell¹ , Melissa A Alexander¹ , Marie-Louise Hammarskjöld¹ , David Rekosh¹ and David Camerini²

¹  Department of Microbiology and Myles H. Thaler Center for AIDS and Human Retrovirus Research, University of Virginia, Charlottesville, VA 22908, USA

²  Department of Molecular Biology and Biochemistry, Center for Immunology and Center for Virus Research, University of California, Irvine, CA 92697-3900, USA

author email corresponding author email

Retrovirology 2008, 5:42doi:10.1186/1742-4690-5-42

Published:	29 May 2008

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.