PMID- 18367527
OWN - NLM
STAT- MEDLINE
DCOM- 20080611
LR  - 20211020
IS  - 1098-5514 (Electronic)
IS  - 0022-538X (Print)
IS  - 0022-538X (Linking)
VI  - 82
IP  - 11
DP  - 2008 Jun
TI  - A fusion inhibitor prevents spread of immunodeficiency viruses, but not 
      activation of virus-specific T cells, by dendritic cells.
PG  - 5329-39
LID - 10.1128/JVI.01987-07 [doi]
AB  - Dendritic cells (DCs) play a key role in innate immune responses, and their 
      interactions with T cells are critical for the induction of adaptive immunity. 
      However, immunodeficiency viruses are efficiently captured by DCs and can be 
      transmitted to and amplified in CD4(+) T cells, with potentially deleterious 
      effects on the induction of immune responses. In DC-T-cell cocultures, contact 
      with CD4(+), not CD8(+), T cells preferentially facilitated virus movement to and 
      release at immature and mature DC-T-cell contact sites. This occurred within 5 
      min of DC-T-cell contact. While the fusion inhibitor T-1249 did not prevent virus 
      capture by DCs or the release of viruses at the DC-T-cell contact points, it 
      readily blocked virus transfer to and amplification in CD4(+) T cells. Higher 
      doses of T-1249 were needed to block the more robust replication driven by mature 
      DCs. Virus accumulated in DCs within T-1249-treated cocultures but these DCs were 
      actually less infectious than DCs isolated from untreated cocultures. 
      Importantly, T-1249 did not interfere with the stimulation of virus-specific 
      CD4(+) and CD8(+) T-cell responses when present during virus-loading of DCs or 
      for the time of the DC-T-cell coculture. These results provide clues to 
      identifying strategies to prevent DC-driven virus amplification in CD4(+) T cells 
      while maintaining virus-specific immunity, an objective critical in the 
      development of microbicides and therapeutic vaccines.
FAU - Frank, I
AU  - Frank I
AD  - Center for Biomedical Research, Population Council, New York, New York 10065, 
      USA.
FAU - Stossel, H
AU  - Stossel H
FAU - Gettie, A
AU  - Gettie A
FAU - Turville, S G
AU  - Turville SG
FAU - Bess, J W Jr
AU  - Bess JW Jr
FAU - Lifson, J D
AU  - Lifson JD
FAU - Sivin, I
AU  - Sivin I
FAU - Romani, N
AU  - Romani N
FAU - Robbiani, M
AU  - Robbiani M
LA  - eng
GR  - P01 HD041752/HD/NICHD NIH HHS/United States
GR  - U19 AI065413/AI/NIAID NIH HHS/United States
GR  - HD041752/HD/NICHD NIH HHS/United States
GR  - R01 AI040877/AI/NIAID NIH HHS/United States
GR  - P01 AI052048/AI/NIAID NIH HHS/United States
GR  - AI065413/AI/NIAID NIH HHS/United States
GR  - RR00164/RR/NCRR NIH HHS/United States
GR  - AI052048/AI/NIAID NIH HHS/United States
GR  - U19 AI065412/AI/NIAID NIH HHS/United States
GR  - AI065412/AI/NIAID NIH HHS/United States
GR  - N01CO12400/CA/NCI NIH HHS/United States
GR  - N01-CO-12400/CO/NCI NIH HHS/United States
GR  - AI040877/AI/NIAID NIH HHS/United States
GR  - P51 RR000164/RR/NCRR NIH HHS/United States
GR  - R37 AI040877/AI/NIAID NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20080326
PL  - United States
TA  - J Virol
JT  - Journal of virology
JID - 0113724
RN  - 0 (Antiviral Agents)
RN  - 0 (HIV Envelope Protein gp41)
RN  - 0 (Peptide Fragments)
RN  - 0 (peptide T1249)
SB  - IM
MH  - Animals
MH  - Antiviral Agents/*pharmacology
MH  - Cells, Cultured
MH  - Coculture Techniques
MH  - Dendritic Cells/*drug effects/*immunology/ultrastructure/virology
MH  - Female
MH  - HIV/*physiology
MH  - HIV Envelope Protein gp41/pharmacology
MH  - Humans
MH  - Macaca mulatta
MH  - Male
MH  - Microscopy, Electron, Transmission
MH  - Peptide Fragments/pharmacology
MH  - Simian Immunodeficiency Virus/*physiology
MH  - T-Lymphocytes/*drug effects/*immunology/ultrastructure
MH  - Time Factors
PMC - PMC2395170
EDAT- 2008/03/28 09:00
MHDA- 2008/06/12 09:00
PMCR- 2008/10/01
CRDT- 2008/03/28 09:00
PHST- 2008/03/28 09:00 [pubmed]
PHST- 2008/06/12 09:00 [medline]
PHST- 2008/03/28 09:00 [entrez]
PHST- 2008/10/01 00:00 [pmc-release]
AID - JVI.01987-07 [pii]
AID - 1987-07 [pii]
AID - 10.1128/JVI.01987-07 [doi]
PST - ppublish
SO  - J Virol. 2008 Jun;82(11):5329-39. doi: 10.1128/JVI.01987-07. Epub 2008 Mar 26.