CD4 down-modulation by human immunodeficiency virus type 1 Nef correlates with the efficiency of viral replication and with CD4(+) T-cell depletion in human lymphoid tissue ex vivo

UMMS Affiliation

Department of Pediatrics; Program in Molecular Medicine



Document Type


Medical Subject Headings

Antigens, CD4; *CD4 Lymphocyte Count; Gene Products, nef; HIV-1; Humans; Lymphoid Tissue; *Virus Replication; nef Gene Products, Human Immunodeficiency Virus


Immunology and Infectious Disease | Pediatrics


The human immunodeficiency virus type 1 (HIV-1) Nef protein is an important virulence factor. Nef has several functions, including down-modulation of CD4 and class I major histocompatibility complex cell surface expression, enhancement of virion infectivity, and stimulation of viral replication in peripheral blood mononuclear cells. Nef also increases HIV-1 replication in human lymphoid tissue (HLT) ex vivo. We analyzed recombinant and primary nef alleles with highly divergent activity in different in vitro assays to clarify which of these Nef activities are functionally linked. Our results demonstrate that Nef activity in CD4 down-regulation correlates significantly with the efficiency of HIV-1 replication and with the severity of CD4(+) T-cell depletion in HLT. In conclusion, HIV-1 Nef variants with increased activity in CD4 down-modulation would cause severe depletion of CD4(+) T cells in lymphoid tissues and accelerate AIDS progression.

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Citation: J Virol. 2001 Nov;75(21):10113-7. Link to article on publisher's site

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