PMID- 29723162
OWN - NLM
STAT- MEDLINE
DCOM- 20190910
LR  - 20220720
IS  - 1558-8238 (Electronic)
IS  - 0021-9738 (Print)
IS  - 0021-9738 (Linking)
VI  - 128
IP  - 8
DP  - 2018 Aug 1
TI  - HIV-1 replicates and persists in vaginal epithelial dendritic cells.
PG  - 3439-3444
LID - 98943 [pii]
LID - 10.1172/JCI98943 [doi]
AB  - HIV-1 acquisition occurs most commonly after sexual contact. To establish 
      infection, HIV-1 must infect cells that support high-level replication, namely 
      CD4+ T cells, which are absent from the outermost genital epithelium. Dendritic 
      cells (DCs), present in mucosal epithelia, potentially facilitate HIV-1 
      acquisition. We show that vaginal epithelial DCs, termed CD1a+ VEDCs, are unlike 
      other blood- and tissue-derived DCs because they express langerin but not 
      DC-SIGN, and unlike skin-based langerin+ DC subset Langerhans cells (LCs), they 
      do not harbor Birbeck granules. Individuals primarily acquire HIV-1 that utilizes 
      the CCR5 receptor (termed either R5 or R5X4) during heterosexual transmission, 
      and the mechanism for the block against variants that only use the CXCR4 receptor 
      (classified as X4) remains unclear. We show that X4 as compared with R5 HIV-1 
      shows limited to no replication in CD1a+ VEDCs. This differential replication 
      occurs after fusion, suggesting that receptor usage influences postentry steps in 
      the virus life cycle. Furthermore, CD1a+ VEDCs isolated from HIV-1-infected 
      virologically suppressed women harbor HIV-1 DNA. Thus, CD1a+ VEDCs are 
      potentially infected early during heterosexual transmission and also retain virus 
      during treatment. Understanding the interplay between HIV-1 and CD1a+ VEDCs is 
      important for future prevention and cure strategies.
FAU - Pena-Cruz, Victor
AU  - Pena-Cruz V
AD  - Department of Medicine and.
FAU - Agosto, Luis M
AU  - Agosto LM
AD  - Department of Medicine and.
FAU - Akiyama, Hisashi
AU  - Akiyama H
AD  - Department of Microbiology, Boston University School of Medicine, Boston, 
      Massachusetts, USA.
FAU - Olson, Alex
AU  - Olson A
AD  - Department of Medicine and.
FAU - Moreau, Yvetane
AU  - Moreau Y
AD  - Department of Medicine and.
FAU - Larrieux, Jean-Robert
AU  - Larrieux JR
AD  - Department of Obstetrics and Gynecology, Boston University, Boston, 
      Massachusetts, USA.
FAU - Henderson, Andrew
AU  - Henderson A
AD  - Department of Medicine and.
FAU - Gummuluru, Suryaram
AU  - Gummuluru S
AD  - Department of Microbiology, Boston University School of Medicine, Boston, 
      Massachusetts, USA.
FAU - Sagar, Manish
AU  - Sagar M
AD  - Department of Medicine and.
LA  - eng
GR  - K24 AI145661/AI/NIAID NIH HHS/United States
GR  - P30 AI042853/AI/NIAID NIH HHS/United States
GR  - R01 AI064099/AI/NIAID NIH HHS/United States
GR  - R01 AI122209/AI/NIAID NIH HHS/United States
PT  - Clinical Trial
PT  - Journal Article
PT  - Multicenter Study
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20180709
PL  - United States
TA  - J Clin Invest
JT  - The Journal of clinical investigation
JID - 7802877
RN  - 0 (CCR5 protein, human)
RN  - 0 (CXCR4 protein, human)
RN  - 0 (Receptors, CCR5)
RN  - 0 (Receptors, CXCR4)
SB  - IM
CIN - J Clin Invest. 2018 Aug 1;128(8):3228-3230. PMID: 29985165
MH  - Adult
MH  - CD4-Positive T-Lymphocytes/immunology/pathology
MH  - Female
MH  - HIV Infections/*immunology/pathology
MH  - HIV-1/*physiology
MH  - Humans
MH  - *Langerhans Cells/immunology/pathology/virology
MH  - Mucous Membrane/immunology/pathology/virology
MH  - Receptors, CCR5/*immunology
MH  - Receptors, CXCR4/*immunology
MH  - Virus Replication/*immunology
PMC - PMC6063466
OTO - NOTNLM
OT  - AIDS/HIV
OT  - Dendritic cells
OT  - Infectious disease
COIS- Conflict of interest: The authors have declared that no conflict of interest 
      exists.
EDAT- 2018/05/04 06:00
MHDA- 2019/09/11 06:00
PMCR- 2018/08/01
CRDT- 2018/05/04 06:00
PHST- 2017/11/29 00:00 [received]
PHST- 2018/05/01 00:00 [accepted]
PHST- 2018/05/04 06:00 [pubmed]
PHST- 2019/09/11 06:00 [medline]
PHST- 2018/05/04 06:00 [entrez]
PHST- 2018/08/01 00:00 [pmc-release]
AID - 98943 [pii]
AID - 10.1172/JCI98943 [doi]
PST - ppublish
SO  - J Clin Invest. 2018 Aug 1;128(8):3439-3444. doi: 10.1172/JCI98943. Epub 2018 Jul 
      9.