J Bacteriol Virol.  2004 Jun;34(2):157-166.

HIV-1 Infection Causes Intracellular Expression of p53, Which Induces PKR Expression, Followed by Inhibition of HIV-1 Tat Activity

Affiliations
  • 1Department of Microbiology, Hannam University, Deajeon 306-749, Korea. ysbae04@skku.edu
  • 2Department of Life Science, Sungkyunkwan University Suwon Gyounggi-do 440-746, Korea.

Abstract

Few papers have reported that the HIV-1 replication was inhibited by p53 in the infected cells. However, the detail mechanism for the p53-medicated HIV-1 suppression has not yet been clearly demonstrated. In our previous report, we addressed that p53-mediated Tat suppression is very likely associated with PKR. In the present study, we found that the amounts of p53 in the HIV-1 infected cells increased over 10 times in the early stages of infection as much as those in normal cells. Particularly noteworthy is that the both exogenous p53 and endogenous p53 enhanced PKR expression in the transformed or treated cells, and the amounts of PKR induced by p53 were almost equivalent to those induced by interferon. In the PKR promoter studies using Ppkr-CAT (CAT reporter system under the control of PKR promoter), CAT activity induced by p53 was stronger than that by interferon, suggesting that the p53-mediated PKR expression might be more efficient than interferon under the control of PKR promoter. Co-immunoprecipitation experiments showed that PKR directly binds to Tat protein. We established eIF-2alpha dominant negative (S51A) Jurkat cells (JK/eIF2alpha-51A) to block the PKR-mediated cell cycle arrest or apoptosis. In the JK/eIF2alpha-51A cells, not only p53 but also PKR inhibited the Tat activity. Taken together, our results demonstrate that the HIV-1 infection induces p53, which enhances PKR expression by promoter activation, followed by the inhibition of the Tat activity, finally resulting in the inhibition of HIV-1 replication. Detail mechanisms for the PKR-mediated Tat inactivation are under investigation.

Keyword

HIV-1 p53; Tat; PKR

MeSH Terms

Animals
Apoptosis
Cats
Cell Cycle Checkpoints
Eukaryotic Initiation Factor-2
Gene Products, tat
HIV-1*
Humans
Immunoprecipitation
Interferons
Jurkat Cells
Eukaryotic Initiation Factor-2
Gene Products, tat
Interferons
Full Text Links
  • JBV
Actions
Cited
CITED
export Copy
Close
Share
  • Twitter
  • Facebook
Similar articles
Copyright © 2023 by Korean Association of Medical Journal Editors. All rights reserved.     E-mail: koreamed@kamje.or.kr