Trans-activation of the human immunodeficiency virus long terminal repeat sequences, expressed in an adenovirus vector, by the adenovirus E1A 13S protein.

Abstract

The human immunodeficiency virus 1 (HIV-1) long terminal repeat (LTR) sequences were inserted into adenovirus in place of the E1 region. The HIV-1 LTR contained in this recombinant adenovirus responds to trans-activation by tatIII in a HeLa cell line constitutively expressing that HIV-1 gene product. In addition, the HIV-1 LTR is activated by the adenovirus E1A 13S, but not 12S or 9S, gene product when it is supplied in trans by a coinfecting wild-type adenovirus. The Rous sarcoma virus LTR, in a similar recombinant adenovirus, is insensitive to tatIII but is also trans-activated by the E1A 13S protein. The action of the 13S E1A and tatIII proteins are additive for the HIV-1 LTR in the context of adenovirus and they appear to act at the transcriptional level. As in HeLa cells, the adenovirus-borne HIV-1 LTR is inactive in the absence of a trans-activator in H9 and Jurkat cells, two human leukemic T-cell lines. This suggests that recombinant adenoviruses have diagnostic potential for the detection of trans-activators of the HIV-1 LTR that are present in circulating human lymphocytes.

Synergy between HIV-1 Tat and adenovirus E1A is principally due to stabilization of transcriptional elongation.

“…This correlation imphes that up to a limit, each RNA molecule gives rise to more CAT enzyme at high RNA concentration than at low RNA concentration, regardless of the presence or absence of Tat. This interpretation is consistent with previous data indicating that Tat has no direct effect on CAT RNA translation (Rice and Mathews 1988a). Another interpretation, which in our view is less likely, is that Tat and ElA act separately to increase the utilization of TAR CAT mRNA.…”

“…One class of activator interacts with upstream cis-regulatory DNA elements to increase transcriptional initiation. These activators include NF-KB, which interacts with the core enhancer (Nabel and Baltimore 1987); Spl, which has binding sites upstream of the HIV-1 promoter (Jones et al 1986); and the adenovirus EIA protein, which interacts with the TATA element (Jones et al 1988;Nabel et al 1988;Rice and Mathews 1988b). The second class of activator consists of the HIV-1 Tat protein and its homologs from HIV-2 and SIV, which bind to a cis-regulatory RNA element, TAR, in nascent transcripts.…”

“…In the experiments described here. Tat was expressed constitutively in HeLa cells from an integrated Tat cDNA under the control of the SV40 early promoter [HeLa/tat-, Valerie et al 1988), and El A was supplied by coinfection with phenotypically wild-type adenovirus (Rice and Mathews 1988b).…”

“…Tat produces a large stimulation of HIV-1-promoted RNA levels (CuUen 1986;Peterlin et al 1986;Wright et al 1986;Hauber et al 1987;Muesing et al 1987;Rice and Mathews 1988a) so the predominant mode of regulation appears to be transcriptional (Hauber et al 1987;Kao et al 1987;Jakobovits et al 1988;Jeang et al 1988;Rice and Mathews 1988a;Sadaie et al 1988;Laspia et al 1989), but evidence for posttranscriptional regulation also exists (Cullen 1986;Fein-Cold Spring Harbor Laboratory Press on April 4, 2019 -Published by genesdev.cshlp.org Downloaded from berg et al 1986;Rosen et al 1986;Wright et al 1986;Braddock et al 1989Braddock et al , 1990). In a model system consisting of replicating plasmids in COS cells, Kao et al (1987) found that Tat does not increase the initiation of transcription but act to stimulate transcriptional elongation.…”

In Vitro and In Vivo Transactivation of HIV-1 by Human Herpesvirus 6

“…The IE protein of pseudorabies virus induces the overproduction of Sp1 (Yuan et al, 1989). Papovaviruses (JC, BK) transactivate through Sp1 (Gendelman et al, 1986), adenovirus (AdV) E1A 13S protein exerts activation on the TATA box and Sp1 sites (Nabel et al, 1988;Rice & Mathews, 1988). Vaccinia virus (Stellrecht et al, 1992), hepatitis B virus (HBV) X protein (Seto et al, 1988), and a retrovirus named human T lymphotropic virus type I (HTLV-I) tax polypeptide (Siekievitz et al, 1987) transactivate HIV-1.…”