J Infect Dis. 2000 Jan;181(1):76-81.

Elevated tumor necrosis factor-alpha activation of human immunodeficiency virus type 1 subtype C in Southern Africa is associated with an NF-kappaB enhancer gain-of-function.

Montano MA, Nixon CP, Ndung'u T, Bussmann H, Novitsky VA, Dickman D, Essex M.

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Department of Immunology, Harvard School of Public Health, Boston, Massachusetts 02115, USA.

Abstract

The human immunodeficiency virus type 1 (HIV-1) epidemic within southern Africa is predominantly associated with the HIV-1C subtype. Functional analysis of the enhancer region within the long terminal repeat (LTR) indicates that HIV-1C isolates have >/=3 NF-kappaB binding sites, unlike other subtypes, which have only 1 or 2 sites. A correlation was shown between NF-kappaB enhancer configuration and responsiveness to the proinflammatory cytokine tumor necrosis factor (TNF)-alpha within the context of naturally occurring subtype LTRs, subtype-specific NF-kappaB enhancer regions cloned upstream of an isogenic HXB2 core promoter or a heterologous SV40 minimal promoter, and full-genome subtype clones. In all cases, TNF-alpha activation was correlated with the subtype configuration of the NF-kappaB enhancer. Whether the naturally occurring gain-of-function in the NF-kappaB enhancer of HIV-1C observed in this study can provide a selective advantage for the virus in vivo remains to be determined and warrants further study.

PMID:: 10608753; [PubMed - indexed for MEDLINE]

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Elevated tumor necrosis factor-alpha activation of human immunodeficiency virus type 1 subtype C in Southern Africa is associated with an NF-kappaB enhancer gain-of-function.

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