PMID- 32784426
OWN - NLM
STAT- MEDLINE
DCOM- 20210223
LR  - 20210310
IS  - 1999-4915 (Electronic)
IS  - 1999-4915 (Linking)
VI  - 12
IP  - 8
DP  - 2020 Aug 8
TI  - Efficient Non-Epigenetic Activation of HIV Latency through the T-Cell Receptor 
      Signalosome.
LID - 10.3390/v12080868 [doi]
LID - 868
AB  - Human immunodeficiency virus type-1 (HIV-1) can either undergo a lytic pathway to 
      cause productive systemic infections or enter a latent state in which the 
      integrated provirus remains transcriptionally silent for decades. The ability to 
      latently infect T-cells enables HIV-1 to establish persistent infections in 
      resting memory CD4+ T-lymphocytes which become reactivated following the 
      disruption or cessation of intensive drug therapy. The maintenance of viral 
      latency occurs through epigenetic and non-epigenetic mechanisms. Epigenetic 
      mechanisms of HIV latency regulation involve the deacetylation and methylation of 
      histone proteins within nucleosome 1 (nuc-1) at the viral long terminal repeats 
      (LTR) such that the inhibition of histone deacetyltransferase and histone lysine 
      methyltransferase activities, respectively, reactivates HIV from latency. 
      Non-epigenetic mechanisms involve the nuclear restriction of critical cellular 
      transcription factors such as nuclear factor-kappa beta (NF-kappaB) or nuclear factor 
      of activated T-cells (NFAT) which activate transcription from the viral LTR, 
      limiting the nuclear levels of the viral transcription transactivator protein Tat 
      and its cellular co-factor positive transcription elongation factor b (P-TEFb), 
      which together regulate HIV transcriptional elongation. In this article, we 
      review how T-cell receptor (TCR) activation efficiently induces NF-kappaB, NFAT, and 
      activator protein 1 (AP-1) transcription factors through multiple signal pathways 
      and how these factors efficiently regulate HIV LTR transcription through the 
      non-epigenetic mechanism. We further discuss how elongation factor P-TEFb, 
      induced through an extracellular signal-regulated kinase (ERK)-dependent 
      mechanism, regulates HIV transcriptional elongation before new Tat is synthesized 
      and the role of AP-1 in the modulation of HIV transcriptional elongation through 
      functional synergy with NF-kappaB. Furthermore, we discuss how TCR signaling induces 
      critical post-translational modifications of the cyclin-dependent kinase 9 (CDK9) 
      subunit of P-TEFb which enhances interactions between P-TEFb and the viral Tat 
      protein and the resultant enhancement of HIV transcriptional elongation.
FAU - Hokello, Joseph
AU  - Hokello J
AUID- ORCID: 0000-0002-6721-5933
AD  - Department of Basic Science, Faculty of Science and Technology, Kampala 
      International University-Western Campus, P.O Box 71, Bushenyi, Uganda.
FAU - Sharma, Adhikarimayum Lakhikumar
AU  - Sharma AL
AUID- ORCID: 0000-0002-9969-8642
AD  - Center for Translational Medicine, Thomas Jefferson University, 1020 Locust 
      Street, Philadelphia, PA 19107, USA.
FAU - Tyagi, Mudit
AU  - Tyagi M
AUID- ORCID: 0000-0003-1493-8051
AD  - Center for Translational Medicine, Thomas Jefferson University, 1020 Locust 
      Street, Philadelphia, PA 19107, USA.
LA  - eng
GR  - R01 DA041746/DA/NIDA NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Review
DEP - 20200808
PL  - Switzerland
TA  - Viruses
JT  - Viruses
JID - 101509722
RN  - 0 (NF-kappa B)
RN  - 0 (NFATC Transcription Factors)
RN  - 0 (Receptors, Antigen, T-Cell)
RN  - 0 (Transcription Factor AP-1)
SB  - IM
MH  - CD4-Positive T-Lymphocytes/virology
MH  - HIV Infections/*virology
MH  - HIV Long Terminal Repeat
MH  - HIV-1/genetics/*physiology
MH  - Humans
MH  - NF-kappa B/metabolism
MH  - NFATC Transcription Factors/metabolism
MH  - Receptors, Antigen, T-Cell/*metabolism
MH  - Signal Transduction
MH  - Transcription Factor AP-1/metabolism
MH  - Transcription, Genetic
MH  - *Virus Latency
PMC - PMC7472175
OTO - NOTNLM
OT  - HIV
OT  - latency
OT  - non-epigenetics
OT  - reactivation
OT  - transcription factors
COIS- The authors declare no conflict of interest. The funders had no role in the study 
      design, data collection and analysis, decision to publish, or preparation of the 
      manuscript.
EDAT- 2020/08/14 06:00
MHDA- 2021/02/24 06:00
PMCR- 2020/08/01
CRDT- 2020/08/14 06:00
PHST- 2020/07/10 00:00 [received]
PHST- 2020/08/05 00:00 [revised]
PHST- 2020/08/06 00:00 [accepted]
PHST- 2020/08/14 06:00 [entrez]
PHST- 2020/08/14 06:00 [pubmed]
PHST- 2021/02/24 06:00 [medline]
PHST- 2020/08/01 00:00 [pmc-release]
AID - v12080868 [pii]
AID - viruses-12-00868 [pii]
AID - 10.3390/v12080868 [doi]
PST - epublish
SO  - Viruses. 2020 Aug 8;12(8):868. doi: 10.3390/v12080868.