The effect of CD4 receptor downregulation and its downstream signaling molecules on HIV-1 latency

Kyung Chang Kim, Hyeon Guk Kim, Tae Young Roh, Jihwan Park, Kyung Min Jung, Joo Shil Lee, Sang-Yun Choi, Sung Soon Kim, Byeong Sun Choi

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

HIV-1 can establish a latent infection in memory CD4+T cells to evade the host immune response. CD4 molecules can act not only as the HIV-1 receptor for entry but also as the trigger in an intracellular signaling cascade for T-cell activation and proliferation via protein tyrosine kinases. Novel chronic HIV-1-infected A3.01-derived (NCHA) cells were used to examine the involvement of CD4 downstream signaling in HIV-1 latency. CD4 receptors in NCHA cells were dramatically downregulated on its surface but were slightly decreased in whole-cell lysates. The expression levels of CD4 downstream signaling molecules, including P56Lck, ZAP-70, LAT, and c-Jun, were sharply decreased in NCHA cells. The lowered histone modifications of H3K4me3 and H3K9ac correlated with the downregulation of P56Lck, ZAP-70, and LAT in NCHA cells. AP-1 binding activity was also reduced in NCHA cells. LAT and c-Jun suppressed in NCHA cells were highly induced after PMA treatment. In epigenetic analysis, other signal transduction molecules which are associated with active and/or latent HIV-1 infection showed normal states in HIV-1 latently infected cells compared to A3.01 cells. In conclusion, we demonstrated that the HIV-1 latent state is sustained by the reduction of downstream signaling molecules via the downregulation of CD4 and the attenuated activity of transcription factor as AP-1. The HIV-1 latency model via T-cell deactivation may provide some clues for the development of the new antireservoir therapy.

Original languageEnglish
Pages (from-to)646-651
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume404
Issue number2
DOIs
Publication statusPublished - 2011 Jan 14

Fingerprint

CD4 Antigens
T-cells
HIV-1
Down-Regulation
Molecules
Transcription Factor AP-1
Signal transduction
Histones
Protein-Tyrosine Kinases
Transcription Factors
Chemical activation
Data storage equipment
T-Lymphocytes
HIV Receptors
Histone Code
Epigenomics
HIV Infections
Signal Transduction

Keywords

  • AP-1
  • CD4 receptor
  • Deactivation
  • NCHA cells
  • Signaling molecular
  • ZAP-70

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Cell Biology
  • Molecular Biology

Cite this

The effect of CD4 receptor downregulation and its downstream signaling molecules on HIV-1 latency. / Kim, Kyung Chang; Kim, Hyeon Guk; Roh, Tae Young; Park, Jihwan; Jung, Kyung Min; Lee, Joo Shil; Choi, Sang-Yun; Kim, Sung Soon; Choi, Byeong Sun.

In: Biochemical and Biophysical Research Communications, Vol. 404, No. 2, 14.01.2011, p. 646-651.

Research output: Contribution to journalArticle

Kim, Kyung Chang ; Kim, Hyeon Guk ; Roh, Tae Young ; Park, Jihwan ; Jung, Kyung Min ; Lee, Joo Shil ; Choi, Sang-Yun ; Kim, Sung Soon ; Choi, Byeong Sun. / The effect of CD4 receptor downregulation and its downstream signaling molecules on HIV-1 latency. In: Biochemical and Biophysical Research Communications. 2011 ; Vol. 404, No. 2. pp. 646-651.
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