Nef does not contribute to replication differences between R5 pre-AIDS and AIDS HIV-1 clones from patient ACH142.
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 123, 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.
Department of Molecular Biology and Biochemistry, Center for Immunology and Center for Virus Research, University of California, Irvine, CA 92697-3900, USA. Kevin_Olivieri@dfci.harvard.edu
Kevin C
KC
Olivieri
Robert M
RM
Scoggins
Brooks
B
Broderick
Maria L C
ML
Powell
Melissa A
MA
Alexander
Marie-Louise
ML
Hammarskjöld
David
D
Rekosh
David
D
Camerini
D000595:Amino Acid Sequence; D015704:CD4 Antigens / Q000096:biosynthesis; D003001:Cloning, Molecular; D003588:Cytopathogenic Effect, Viral; D015536:Down-Regulation; D015658:HIV Infections / Q000821:virology*; D015497:HIV-1 / Q000235:genetics / Q000254:growth & development / Q000472:pathogenicity / Q000502:physiology*; D015395:Histocompatibility Antigens Class I / Q000096:biosynthesis; D006801:Humans; D008969:Molecular Sequence Data; D016415:Sequence Alignment; D014779:Virus Replication; D054311:nef Gene Products, Human Immunodeficiency Virus / Q000235:genetics / Q000502:physiology*
D015704:CD4 Antigens; D015395:Histocompatibility Antigens Class I; D054311:nef Gene Products, Human Immunodeficiency Virus; C514837:nef protein, Human immunodeficiency virus 1