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 language | English |
|---|---|
| Pages (from-to) | 646-651 |
| Number of pages | 6 |
| Journal | Biochemical and Biophysical Research Communications |
| Volume | 404 |
| Issue number | 2 |
| DOIs | |
| Publication status | Published - 2011 Jan 14 |
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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 journal › Article
}
TY - JOUR
T1 - The effect of CD4 receptor downregulation and its downstream signaling molecules on HIV-1 latency
AU - Kim, Kyung Chang
AU - Kim, Hyeon Guk
AU - Roh, Tae Young
AU - Park, Jihwan
AU - Jung, Kyung Min
AU - Lee, Joo Shil
AU - Choi, Sang-Yun
AU - Kim, Sung Soon
AU - Choi, Byeong Sun
PY - 2011/1/14
Y1 - 2011/1/14
N2 - 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.
AB - 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.
KW - AP-1
KW - CD4 receptor
KW - Deactivation
KW - NCHA cells
KW - Signaling molecular
KW - ZAP-70
UR - http://www.scopus.com/inward/record.url?scp=78651360646&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=78651360646&partnerID=8YFLogxK
U2 - 10.1016/j.bbrc.2010.12.032
DO - 10.1016/j.bbrc.2010.12.032
M3 - Article
VL - 404
SP - 646
EP - 651
JO - The BMJ
JF - The BMJ
SN - 0730-6512
IS - 2
ER -