PMID- 21738472
OWN - NLM
STAT- MEDLINE
DCOM- 20111228
LR  - 20211020
IS  - 1553-7374 (Electronic)
IS  - 1553-7366 (Print)
IS  - 1553-7366 (Linking)
VI  - 7
IP  - 6
DP  - 2011 Jun
TI  - HSV-2 infection of dendritic cells amplifies a highly susceptible HIV-1 cell 
      target.
PG  - e1002109
LID - 10.1371/journal.ppat.1002109 [doi]
LID - e1002109
AB  - Herpes simplex virus type 2 (HSV-2) increases the risk of HIV-1 infection and, 
      although several reports describe the interaction between these two viruses, the 
      exact mechanism for this increased susceptibility remains unclear. Dendritic 
      cells (DCs) at the site of entry of HSV-2 and HIV-1 contribute to viral spread in 
      the mucosa. Specialized DCs present in the gut-associated lymphoid tissues 
      produce retinoic acid (RA), an important immunomodulator, able to influence HIV-1 
      replication and a key mediator of integrin alpha(4)beta(7) on lymphocytes. alpha(4)beta(7) can be 
      engaged by HIV-1 on the cell-surface and CD4(+) T cells expressing high levels of 
      this integrin (alpha(4)beta(7) (high)) are particularly susceptible to HIV-1 infection. 
      Herein we provide in-vivo data in macaques showing an increased percentage of 
      alpha(4)beta(7) (high) CD4(+) T cells in rectal mucosa, iliac lymph nodes and blood within 6 
      days of rectal exposure to live (n = 11), but not UV-treated (n = 8), HSV-2. We 
      found that CD11c(+) DCs are a major target of HSV-2 infection in in-vitro exposed 
      PBMCs. We determined that immature monocyte-derived DCs (moDCs) express aldehyde 
      dehydrogenase ALDH1A1, an enzyme essential for RA production, which increases 
      upon HSV-2 infection. Moreover, HSV-2-infected moDCs significantly increase alpha(4)beta(7) 
      expression on CD4(+) T lymphocytes and HIV-1 infection in DC-T cell mixtures in a 
      RA-dependent manner. Thus, we propose that HSV-2 modulates its microenviroment, 
      influencing DC function, increasing RA production capability and amplifying a 
      alpha(4)beta(7) (high)CD4(+) T cells. These factors may play a role in increasing the 
      susceptibility to HIV-1.
FAU - Martinelli, Elena
AU  - Martinelli E
AD  - Center for Biomedical Research, Population Council, New York, New York, United 
      States of America. emartinelli@popcouncil.org
FAU - Tharinger, Hugo
AU  - Tharinger H
FAU - Frank, Ines
AU  - Frank I
FAU - Arthos, James
AU  - Arthos J
FAU - Piatak, Michael Jr
AU  - Piatak M Jr
FAU - Lifson, Jeffrey D
AU  - Lifson JD
FAU - Blanchard, James
AU  - Blanchard J
FAU - Gettie, Agegnehu
AU  - Gettie A
FAU - Robbiani, Melissa
AU  - Robbiani M
LA  - eng
GR  - P51 OD011104/OD/NIH HHS/United States
GR  - RR00164/RR/NCRR NIH HHS/United States
GR  - HHSN261200800001C/RC/CCR NIH HHS/United States
GR  - HHSN261200800001E/CA/NCI 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
DEP - 20110630
PL  - United States
TA  - PLoS Pathog
JT  - PLoS pathogens
JID - 101238921
RN  - 0 (CD11c Antigen)
RN  - 0 (Integrins)
RN  - 0 (integrin alpha4beta7)
RN  - 5688UTC01R (Tretinoin)
SB  - IM
MH  - Animals
MH  - CD11c Antigen/immunology
MH  - CD4-Positive T-Lymphocytes/metabolism/pathology/*virology
MH  - Coinfection/*virology
MH  - Dendritic Cells/*pathology/virology
MH  - Disease Susceptibility/pathology
MH  - HIV Infections/complications/*virology
MH  - *HIV-1
MH  - Herpes Genitalis/complications/*virology
MH  - *Herpesvirus 2, Human
MH  - Integrins/metabolism
MH  - Lymph Nodes
MH  - Macaca
MH  - Mucous Membrane/pathology/virology
MH  - Rectum
MH  - Tretinoin/metabolism
PMC - PMC3128120
COIS- The authors have declared that no competing interests exist.
EDAT- 2011/07/09 06:00
MHDA- 2011/12/29 06:00
PMCR- 2011/06/30
CRDT- 2011/07/09 06:00
PHST- 2010/11/11 00:00 [received]
PHST- 2011/04/23 00:00 [accepted]
PHST- 2011/07/09 06:00 [entrez]
PHST- 2011/07/09 06:00 [pubmed]
PHST- 2011/12/29 06:00 [medline]
PHST- 2011/06/30 00:00 [pmc-release]
AID - PPATHOGENS-D-10-00305 [pii]
AID - 10.1371/journal.ppat.1002109 [doi]
PST - ppublish
SO  - PLoS Pathog. 2011 Jun;7(6):e1002109. doi: 10.1371/journal.ppat.1002109. Epub 2011 
      Jun 30.