PMID- 21698207
OWN - NLM
STAT- MEDLINE
DCOM- 20111107
LR  - 20211020
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 6
IP  - 6
DP  - 2011
TI  - Exposure to apoptotic activated CD4+ T cells induces maturation and 
      APOBEC3G-mediated inhibition of HIV-1 infection in dendritic cells.
PG  - e21171
LID - 10.1371/journal.pone.0021171 [doi]
LID - e21171
AB  - Dendritic cells (DCs) are activated by signaling via pathogen-specific receptors 
      or exposure to inflammatory mediators. Here we show that co-culturing DCs with 
      apoptotic HIV-infected activated CD4(+) T cells (ApoInf) or apoptotic uninfected 
      activated CD4(+) T cells (ApoAct) induced expression of co-stimulatory molecules 
      and cytokine release. In addition, we measured a reduced HIV infection rate in 
      DCs after co-culture with ApoAct. A prerequisite for reduced HIV infection in DCs 
      was activation of CD4(+) T cells before apoptosis induction. DCs exposed to 
      ApoAct or ApoInf secreted MIP-1alpha, MIP-1beta, MCP-1, and TNF-alpha; this effect was 
      retained in the presence of exogenous HIV. The ApoAct-mediated induction of 
      co-stimulatory CD86 molecules and reduction of HIV infection in DCs were 
      partially abrogated after blocking TNF-alpha using monoclonal antibodies. APOBEC3G 
      expression in DCs was increased in co-cultures of DCs and ApoAct but not by 
      apoptotic resting CD4(+) T cells (ApoRest). Silencing of APOBEC3G in DC abrogated 
      the HIV inhibitory effect mediated by ApoAct. Sequence analyses of an env region 
      revealed significant induction of G-to-A hypermutations in the context of GG or 
      GA dinucleotides in DNA isolated from DCs exposed to HIV and ApoAct. Thus, 
      ApoAct-mediated DC maturation resulted in induction of APOBEC3G that was 
      important for inhibition of HIV-infection in DCs. These findings underscore the 
      complexity of differential DC responses evoked upon interaction with resting as 
      compared with activated dying cells during HIV infection.
FAU - Mohanram, Venkatramanan
AU  - Mohanram V
AD  - Center for Infectious Medicine, Department of Medicine, Karolinska Institutet, 
      Karolinska University Hospital Huddinge, Stockholm, Sweden.
FAU - Johansson, Ulrika
AU  - Johansson U
FAU - Skold, Annette E
AU  - Skold AE
FAU - Fink, Joshua
AU  - Fink J
FAU - Kumar Pathak, Sushil
AU  - Kumar Pathak S
FAU - Makitalo, Barbro
AU  - Makitalo B
FAU - Walther-Jallow, Lilian
AU  - Walther-Jallow L
FAU - Spetz, Anna-Lena
AU  - Spetz AL
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20110616
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Chemokines)
RN  - 0 (Culture Media, Conditioned)
RN  - 0 (Cytokines)
RN  - 0 (DNA Primers)
RN  - EC 3.5.4.5 (APOBEC-3G Deaminase)
RN  - EC 3.5.4.5 (APOBEC3G protein, human)
RN  - EC 3.5.4.5 (Cytidine Deaminase)
SB  - IM
MH  - APOBEC-3G Deaminase
MH  - *Apoptosis
MH  - Base Sequence
MH  - CD4-Positive T-Lymphocytes/*cytology
MH  - Cell Differentiation
MH  - Chemokines/metabolism
MH  - Coculture Techniques
MH  - Culture Media, Conditioned
MH  - Cytidine Deaminase/*physiology
MH  - Cytokines/metabolism
MH  - DNA Primers
MH  - Dendritic Cells/cytology/*virology
MH  - Humans
MH  - Polymerase Chain Reaction
PMC - PMC3116862
COIS- Competing Interests: A.-L. Spetz and L. Walther-Jallow have affiliation with 
      Avaris AB. This does not alter the authors' adherence to the PLoS ONE policies on 
      sharing data and materials.
EDAT- 2011/06/24 06:00
MHDA- 2011/11/08 06:00
PMCR- 2011/06/16
CRDT- 2011/06/24 06:00
PHST- 2010/12/10 00:00 [received]
PHST- 2011/05/21 00:00 [accepted]
PHST- 2011/06/24 06:00 [entrez]
PHST- 2011/06/24 06:00 [pubmed]
PHST- 2011/11/08 06:00 [medline]
PHST- 2011/06/16 00:00 [pmc-release]
AID - PONE-D-10-06394 [pii]
AID - 10.1371/journal.pone.0021171 [doi]
PST - ppublish
SO  - PLoS One. 2011;6(6):e21171. doi: 10.1371/journal.pone.0021171. Epub 2011 Jun 16.