Human herpes virus-6 increases HIV-1 expression in co-infected T cells via nuclear factors binding to the HIV-1 enhancer

EMBO J. 1989 Oct;8(10):3019-27. doi: 10.1002/j.1460-2075.1989.tb08452.x.

Abstract

Human Herpes virus-6 (HHV-6) can co-infect with HIV-1 human CD4+ T-cells, leading to accelerated cell death, and factors in HHV-6-infected cells stimulate HIV-1 LTR directed gene expression. In this study, we have examined the mechanism of HIV-1 activation by HHV-6 and localized the cis-acting sequences of HIV-1 LTR responsive to trans-activation. Increased HIV-1 LTR directed gene expression is obtained in HIV-1 infected cells co-infected with HHV-6, or in HHV-6 infected cells co-transfected with the HIV-1 tat gene. Parallel increases of HIV-1-specific transcripts are seen by in situ hybridization in HHV-6/HIV-1 doubly infected cells as compared to single HIV-1 infection. Similarly, infection by HHV-6 increases the steady-state level of HIV-1 LTR mRNA that parallels CAT enzymatic activity, suggesting a transcriptional and/or post-transcriptional activation. Sequences necessary for HIV-1 LTR activation by HHV-6 are distinct from those required for that tat response and map to a region of the HIV-1 LTR from -103 to -48. The HIV-1 enhancer sequence (-105 to -80) is sufficient to confer HHV-6 inducibility to a heterologous promoter, and nuclear protein(s) activated or induced by HHV-6 infection specifically bind to the NF kappa B motifs of the HIV-1 enhancer region.(ABSTRACT TRUNCATED AT 250 WORDS)

MeSH terms

  • Base Sequence
  • CD4-Positive T-Lymphocytes / microbiology*
  • Cell Line
  • DNA-Binding Proteins / metabolism
  • Enhancer Elements, Genetic*
  • Gene Expression Regulation, Viral
  • Genes, Viral
  • HIV-1 / genetics*
  • HIV-1 / physiology
  • Herpesvirus 6, Human / genetics
  • Herpesvirus 6, Human / physiology*
  • Humans
  • Mutation
  • Nuclear Proteins / metabolism
  • Nucleic Acid Hybridization
  • Promoter Regions, Genetic
  • RNA, Messenger / genetics
  • RNA, Viral / genetics
  • Transcription, Genetic
  • Transcriptional Activation*
  • Transfection
  • Virus Activation

Substances

  • DNA-Binding Proteins
  • Nuclear Proteins
  • RNA, Messenger
  • RNA, Viral