Vpr and Vpu are important for efficient human immunodeficiency virus type 1 replication and CD4+ T-cell depletion in human lymphoid tissue ex vivo.
The relevance of the accessory vpr, vpu, and nef genes for human immunodeficiency virus type 1 (HIV-1) replication in human lymphoid tissue (HLT), the major site of viral replication in vivo, is largely unknown. Here, we show that an individual deletion of nef, vpr, or vpu significantly decreases HIV-1 replication and prevents CD4+ T-cell depletion in ex vivo HLT. However, only combined defects in all three accessory genes entirely disrupt the replicative capacity of HIV-1. Our results demonstrate that nef, vpr, and vpu are all essential for efficient viral spread in HLT, suggesting an important role in AIDS pathogenesis.
Rücker
Elke
E
National Institute of Child Health, Building 10, Room 9D58, Bethesda, MD 20892, USA.
Grivel
Jean-Charles
JC
Münch
Jan
J
Kirchhoff
Frank
F
Margolis
Leonid
L
D015496:CD4-Positive T-Lymphocytes / Q000502:physiology*; D015693:Gene Products, nef / Q000502:physiology; D016336:Gene Products, vpr / Q000502:physiology*; D015497:HIV-1 / Q000502:physiology*; D054298:Human Immunodeficiency Virus Proteins; D006801:Humans; D007376:Interleukin-2 / Q000494:pharmacology; D008221:Lymphoid Tissue / Q000821:virology*; D054334:Viral Regulatory and Accessory Proteins / Q000502:physiology*; D014779:Virus Replication; D054311:nef Gene Products, Human Immunodeficiency Virus; D054325:vpr Gene Products, Human Immunodeficiency Virus; D000086082:Viroporin Proteins
D015693:Gene Products, nef; D016336:Gene Products, vpr; D054298:Human Immunodeficiency Virus Proteins; D007376:Interleukin-2; D054334:Viral Regulatory and Accessory Proteins; D054311:nef Gene Products, Human Immunodeficiency Virus; D054325:vpr Gene Products, Human Immunodeficiency Virus; C514859:vpu protein, Human immunodeficiency virus 1; D000086082:Viroporin Proteins