Functional analysis of the Tat trans activator of human immunodeficiency virus type 2.

Published

Journal Article

The trans-activator (Tat) proteins of the related but distinct type 1 and type 2 human immunodeficiency viruses (HIV-1 and HIV-2) display incomplete functional reciprocity. One possible explanation of this observation, suggested by computer analysis of potential RNA secondary structures within the viral trans-activation response (TAR) elements, is that HIV-2 Tat requires the presentation of two viral RNA stem-loop sequences for full activity whereas HIV-1 Tat is maximally active upon presentation of a single stem-loop structure. Here, we demonstrate that the HIV-2 long terminal repeat indeed contains two functionally independent TAR elements. However, the second (3') TAR element of HIV-2 is significantly less active than the 5' TAR element and is functionally masked in the context of an intact HIV-2 long terminal repeat. Evidence is presented suggesting that the activities of these two HIV-2 TAR elements reflect, at least in part, their relative distances from the site of transcription initiation. Although the HIV-2 TAR element proximal to the viral mRNA cap site appears to be sufficient for effective trans activation by HIV-2 Tat in vitro, this functional redundancy may nevertheless serve to enhance HIV-2 replication in infected cells in vivo.

Full Text

Duke Authors

Cited Authors

  • Fenrick, R; Malim, MH; Hauber, J; Le, SY; Maizel, J; Cullen, BR

Published Date

  • December 1989

Published In

Volume / Issue

  • 63 / 12

Start / End Page

  • 5006 - 5012

PubMed ID

  • 2555537

Pubmed Central ID

  • 2555537

International Standard Serial Number (ISSN)

  • 0022-538X

Language

  • eng

Conference Location

  • United States