PMID- 30523283
OWN - NLM
STAT- MEDLINE
DCOM- 20191016
LR  - 20191206
IS  - 2045-2322 (Electronic)
IS  - 2045-2322 (Linking)
VI  - 8
IP  - 1
DP  - 2018 Dec 6
TI  - Human Herpesvirus 6A and 6B inhibit in vitro angiogenesis by induction of Human 
      Leukocyte Antigen G.
PG  - 17683
LID - 10.1038/s41598-018-36146-0 [doi]
LID - 17683
AB  - We have previously reported that human herpesvirus 6 (HHV-6) infection of 
      endothelial cells (ECs) induces the loss of angiogenic properties, through the 
      expression of HHV-6 U94, possibly associated to the release of a soluble 
      mediator. It is also known that the soluble isoform of HLA-G exhibits an 
      anti-angiogenic function, important in implantation, transplantation and 
      neoplastic development. In this study, we analyzed the expression of HLA-G in 
      HHV-6 infected ECs, showing that both HHV-6A and HHV-6B infection induce a potent 
      up-modulation of HLA-G, including both membrane and soluble isoforms. 
      Interestingly, HHV-6A and HHV-6B induced different isoforms of HLA-G. The 
      virus-induced increase of HLA-G was likely due to the expression of the U94 viral 
      gene, that by itself was able to reproduce the effect of whole virus. The effect 
      of U94 was mediated by human transcription factor ATF3, that induced HLA-G 
      activation by recognizing a consensus sequence on its promoter. Virus-induced 
      inhibition of ECs angiogenic ability directly correlated to HLA-G expression and 
      release, and the addition of anti-HLA-G antibody restored the angiogenic 
      properties of HHV6-infected ECs. The induction of HLA-G expression in ECs might 
      represent an important mediator of HHV-6 induced effects.
FAU - Rizzo, Roberta
AU  - Rizzo R
AD  - Section of Microbiology and Medical Genetics, Department of Medical Sciences, 
      School of Medicine, University of Ferrara, Ferrara, 44121, Italy.
FAU - D'Accolti, Maria
AU  - D'Accolti M
AD  - Section of Microbiology and Medical Genetics, Department of Medical Sciences, 
      School of Medicine, University of Ferrara, Ferrara, 44121, Italy.
FAU - Bortolotti, Daria
AU  - Bortolotti D
AD  - Section of Microbiology and Medical Genetics, Department of Medical Sciences, 
      School of Medicine, University of Ferrara, Ferrara, 44121, Italy.
FAU - Caccuri, Francesca
AU  - Caccuri F
AD  - Section of Microbiology, Department of Molecular and Translational Medicine, 
      University of Brescia Medical School, Brescia, 25123, Italy.
FAU - Caruso, Arnaldo
AU  - Caruso A
AD  - Section of Microbiology, Department of Molecular and Translational Medicine, 
      University of Brescia Medical School, Brescia, 25123, Italy.
FAU - Di Luca, Dario
AU  - Di Luca D
AD  - Section of Microbiology and Medical Genetics, Department of Medical Sciences, 
      School of Medicine, University of Ferrara, Ferrara, 44121, Italy. ddl@unife.it.
FAU - Caselli, Elisabetta
AU  - Caselli E
AUID- ORCID: 0000-0001-6048-9141
AD  - Section of Microbiology and Medical Genetics, Department of Medical Sciences, 
      School of Medicine, University of Ferrara, Ferrara, 44121, Italy. csb@unife.it.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20181206
PL  - England
TA  - Sci Rep
JT  - Scientific reports
JID - 101563288
RN  - 0 (Angiogenesis Inducing Agents)
RN  - 0 (Antibodies)
RN  - 0 (HLA Antigens)
RN  - 0 (HLA-G Antigens)
RN  - 0 (Protein Isoforms)
SB  - IM
MH  - Angiogenesis Inducing Agents/*immunology
MH  - Antibodies/immunology
MH  - Cell Line
MH  - Endothelial Cells/immunology/virology
MH  - Genes, Viral/immunology
MH  - Genome, Viral/immunology
MH  - HLA Antigens/*immunology
MH  - HLA-G Antigens/*immunology
MH  - Herpesvirus 6, Human/*immunology
MH  - Human Umbilical Vein Endothelial Cells/immunology/virology
MH  - Humans
MH  - Protein Isoforms/immunology
MH  - Virus Activation/immunology
PMC - PMC6283866
COIS- The authors declare no competing interests.
EDAT- 2018/12/14 06:00
MHDA- 2019/10/17 06:00
PMCR- 2018/12/06
CRDT- 2018/12/08 06:00
PHST- 2018/07/05 00:00 [received]
PHST- 2018/11/09 00:00 [accepted]
PHST- 2018/12/08 06:00 [entrez]
PHST- 2018/12/14 06:00 [pubmed]
PHST- 2019/10/17 06:00 [medline]
PHST- 2018/12/06 00:00 [pmc-release]
AID - 10.1038/s41598-018-36146-0 [pii]
AID - 36146 [pii]
AID - 10.1038/s41598-018-36146-0 [doi]
PST - epublish
SO  - Sci Rep. 2018 Dec 6;8(1):17683. doi: 10.1038/s41598-018-36146-0.