PMID- 21084994
OWN - NLM
STAT- MEDLINE
DCOM- 20110404
LR  - 20211020
IS  - 1944-7884 (Electronic)
IS  - 1525-4135 (Print)
IS  - 1525-4135 (Linking)
VI  - 56
IP  - 3
DP  - 2011 Mar 1
TI  - Attachment and fusion inhibitors potently prevent dendritic cell-driven HIV 
      infection.
PG  - 204-12
LID - 10.1097/QAI.0b013e3181ff2aa5 [doi]
AB  - Dendritic cells (DCs) efficiently transfer captured (trans) or de novo-produced 
      (cis) virus to CD4 T cells. Using monocyte-derived DCs, we evaluated entry 
      inhibitors targeting HIV envelope (BMS-C, T-1249) or CCR5 (CMPD167) for their 
      potency to prevent DC infection, DC-driven infection in T cells in trans and cis, 
      and direct infection of DC-T-cell mixtures. Immature DC-T-cell cultures with 
      distinct mechanisms of viral transfer yielded similar levels of infection and 
      produced more proviral DNA compared with matched mature DC-T-cell cultures or 
      infected immature DCs. Although all compounds completely blocked HIV replication, 
      16 times more of each inhibitor (250 vs 15.6 nM) was required to prevent 
      low-level infection of DCs compared with the productive DC-T-cell cocultures. 
      Across all cell systems tested, BMS-C blocked infection most potently. BMS-C was 
      significantly more effective than CMPD167 at preventing DC infection. In fact, 
      low doses of CMPD167 significantly enhanced DC infection. Elevated levels of CCL4 
      were observed when immature DCs were cultured with CMPD167. Viral entry 
      inhibitors did not interfere with Candida albicans-specific DC cytokine/chemokine 
      responses. These findings indicate that an envelope-binding small molecule is a 
      promising tool for topical microbicide design to prevent the infection of early 
      targets needed to establish and disseminate HIV infection.
FAU - Frank, Ines
AU  - Frank I
AD  - Center for Biomedical Research, Population Council, New York, NY 10065, USA.
FAU - Robbiani, Melissa
AU  - Robbiani M
LA  - eng
GR  - P01 AI052048-01/AI/NIAID NIH HHS/United States
GR  - R37 AI040877/AI/NIAID NIH HHS/United States
GR  - P01 AI052048/AI/NIAID NIH HHS/United States
GR  - AI052048/AI/NIAID NIH HHS/United States
GR  - U19 AI076982/AI/NIAID NIH HHS/United States
GR  - N01CO12400/CA/NCI NIH HHS/United States
GR  - N01-CO-12400/CO/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Acquir Immune Defic Syndr
JT  - Journal of acquired immune deficiency syndromes (1999)
JID - 100892005
RN  - 0 (Anti-HIV Agents)
RN  - 0 (CMPD 167)
RN  - 0 (HIV Envelope Protein gp41)
RN  - 0 (HIV Fusion Inhibitors)
RN  - 0 (Peptide Fragments)
RN  - 0 (Pyrazoles)
RN  - 0 (peptide T1249)
RN  - HG18B9YRS7 (Valine)
SB  - IM
MH  - Anti-HIV Agents/*pharmacology
MH  - Cells, Cultured
MH  - Coculture Techniques
MH  - Dendritic Cells/*drug effects/*virology
MH  - HIV/*drug effects/*growth & development
MH  - HIV Envelope Protein gp41/pharmacology
MH  - HIV Fusion Inhibitors/*pharmacology
MH  - HIV Infections/*virology
MH  - Humans
MH  - Peptide Fragments/pharmacology
MH  - Pyrazoles/pharmacology
MH  - T-Lymphocytes/drug effects/virology
MH  - Valine/analogs & derivatives/pharmacology
MH  - Virus Replication/drug effects
PMC - PMC3039069
MID - NIHMS253010
EDAT- 2010/11/19 06:00
MHDA- 2011/04/05 06:00
PMCR- 2012/03/01
CRDT- 2010/11/19 06:00
PHST- 2010/11/19 06:00 [entrez]
PHST- 2010/11/19 06:00 [pubmed]
PHST- 2011/04/05 06:00 [medline]
PHST- 2012/03/01 00:00 [pmc-release]
AID - 10.1097/QAI.0b013e3181ff2aa5 [doi]
PST - ppublish
SO  - J Acquir Immune Defic Syndr. 2011 Mar 1;56(3):204-12. doi: 
      10.1097/QAI.0b013e3181ff2aa5.