PMID- 28692540
DCOM- 20180508
LR  - 20180523
IS  - 1473-5571 (Electronic)
IS  - 0269-9370 (Linking)
VI  - 31
IP  - 14
DP  - 2017 Sep 10
TI  - Unique microRNA expression in the colonic mucosa during chronic HIV-1 infection.
PG  - 1925-1934
LID - 10.1097/QAD.0000000000001582 [doi]
AB  - OBJECTIVE: Chronic HIV-1 infection leads to widespread inflammation and immune
      dysregulation. The gastrointestinal mucosa, a primary site for HIV-1 replication,
      is thought to play a significant role in this response. MicroRNAs (miRs) are
      small noncoding RNAs that regulate gene expression, including immune activation
      and inflammation. Here we investigate miR expression and function in the colonic 
      mucosa during HIV-1 infection. DESIGN AND METHODS: Using miR profiling, we
      examined miR expression in the colonic mucosa of HIV-infected patients. These
      miRs were further parsed to identify those that most likely function in
      HIV-related inflammation. Using bioinformatics tools, we identified potential
      target genes which were confirmed using in-vitro functional testing. RESULTS: We 
      identified 12 miRs that were differentially expressed in the colonic mucosa of
      HIV-infected patients with high versus undetectable plasma viral concentrations. 
      Of these, both miR-26a and miR-29a were downregulated in untreated HIV-1
      infection, yet not in the colonic mucosa from inflammatory bowel disease. This
      downregulation occurs within the first hours after infection. These miRs were
      further shown to directly target IL-6 and STAT3, respectively, with similar
      changes confirmed in an ex-vivo explant infection model. CONCLUSION: miR-26a and 
      miR-29a levels are decreased in the colonic mucosa during chronic HIV-1
      infection, and this change may be initiated during acute infection. Both miRs
      de-repress the IL-6/STAT3 signaling pathway, which could contribute to increased 
      inflammation during infection. These miRs may represent novel therapeutic targets
      for HIV-1-associated inflammation in the colonic mucosa.
FAU - Fulcher, Jennifer A
AU  - Fulcher JA
AD  - aDivision of Infectious Diseases bVatche and Tamar Manoukian Division of
      Digestive Diseases cDivision of Hematology-Oncology, Department of Medicine,
      David Geffen School of Medicine at UCLA dCenter for Systems Biomedicine, David
      Geffen School of Medicine at UCLA eUCLA AIDS Institute, Los Angeles, California, 
FAU - Koukos, Georgios
AU  - Koukos G
FAU - Koutsioumpa, Marina
AU  - Koutsioumpa M
FAU - Elliott, Julie
AU  - Elliott J
FAU - Drakaki, Alexandra
AU  - Drakaki A
FAU - Iliopoulos, Dimitrios
AU  - Iliopoulos D
FAU - Anton, Peter A
AU  - Anton PA
LA  - eng
GR  - KL2 TR001882/TR/NCATS NIH HHS/United States
GR  - P30 AI028697/AI/NIAID NIH HHS/United States
GR  - P30 DK041301/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, N.I.H., Extramural
PL  - England
JT  - AIDS (London, England)
JID - 8710219
RN  - 0 (MicroRNAs)
SB  - IM
SB  - X
MH  - Adult
MH  - Aged
MH  - Cohort Studies
MH  - Colon/*pathology
MH  - Female
MH  - *Gene Expression Profiling
MH  - HIV Infections/*pathology
MH  - Humans
MH  - Intestinal Mucosa/*pathology
MH  - Male
MH  - MicroRNAs/*analysis/genetics
MH  - Middle Aged
PMC - PMC5578872
MID - NIHMS892027
EDAT- 2017/07/12 06:00
MHDA- 2018/05/09 06:00
CRDT- 2017/07/11 06:00
PMCR- 2018/09/10 00:00
PHST- 2018/09/10 00:00 [pmc-release]
PHST- 2017/07/12 06:00 [pubmed]
PHST- 2018/05/09 06:00 [medline]
PHST- 2017/07/11 06:00 [entrez]
AID - 10.1097/QAD.0000000000001582 [doi]
PST - ppublish
SO  - AIDS. 2017 Sep 10;31(14):1925-1934. doi: 10.1097/QAD.0000000000001582.