Vpr and Vpu Are Important for Efficient Human Immunodeficiency Virus Type 1 Replication and CD4 + T-Cell Depletion in Human Lymphoid Tissue Ex Vivo

Abstract

ABSTRACT 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.