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Journal of Clinical Microbiology, August 2000, p. 3135-3136, Vol. 38, No. 8
0095-1137/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.
LETTERS TO THE EDITOR
Human Herpesvirus 6 Infects and Replicates in Aortic Endothelium
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LETTER |
Herpesviruses have been proposed as potential mediators of
vascular injury (3). In particular, indirect evidence links human cytomegalovirus (HCMV) infection with the development of vascular
diseases, including coronary artery disease, vascular sclerosis, and
arterial restenosis (2), but a clear role for the virus has
yet to be established. In addition to HCMV, other herpesviruses can
infect endothelial cells. Human herpesvirus 6 (HHV-6) has a
preferential tropism for CD4 T lymphocytes but can infect endothelial
cells in vitro (5).
To investigate a potential role for HHV-6 in vascular diseases,
endothelial cells obtained from aorta, vasa vasorum, and heart microvessel (auricle specimen) from an immunocompetent patient with
aortic insufficiency and aortic aneurysm were cultivated in vitro as
already described (1). Samples were analyzed by nested PCR
for the presence of HHV-6 DNA (4). HHV-6 variant B was
detected in cultured cells from aorta but not from vasa vasorum and
heart microvessels. Viral DNA was not detected in mononuclear cells
purified from peripheral blood.
We have recently reported that HHV-6 latency is associated with the
presence of U94 mRNA in the absence of other mRNAs transcribed during
the immediate-early phase of infection (4). Therefore, to
ascertain whether HHV-6 was latent or productively replicating in the
aortic endothelium, RNA was extracted from the cell cultures 7, 22, and
64 days after explantation and was analyzed by nested reverse
transcription PCR. Viral transcripts from immediate-early (U91, U42)
and late (U22) genes were detected in aortic endothelial cells in all
culture passages (Fig. 1). No residual
DNA contamination of RNA samples was detected by analyzing the same
amount of mRNA, without the initial reverse transcription reaction.
Furthermore, the presence of spliced forms of U91 (283 bp) (Fig. 1)
definitively ruled out the possibility that positive reactions could be
attributed to contamination by residual DNA. Endothelial cells from
microvessels and vasa vasorum did not harbor HHV-6 transcripts (Fig.
1). Cell cultures positive for HHV-6 mRNA were analyzed by indirect
immunofluorescence with monoclonal antibodies to HHV-6 p41 antigen. No
viral antigen was detected, suggesting that HHV-6 supported a low-level
replication in aortic endothelial cells.
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FIG. 1.
Reverse transcription-PCR analysis for HHV-6
transcripts. mRNA was extracted from cultured endothelial cells from
aorta (A), vasa vasorum (V), and auricle microvessels (M),
retrotranscribed and amplified with HHV-6 primers for U91, U42, and
U22. PCR was performed with (RT+) and without (RT ) retrotranscription
on the same samples. The sizes of the amplified bands are shown. Cells
were harvested 7, 22, or 64 days after explantation (lanes 1, 2, and 3, respectively). The spliced form of U91, corresponding to 283 bp, was
present in all positive samples (lanes 1, 2, and 3) but reproduced
poorly in the print. Lane D represents a control of amplification
reaction performed using HHV-6 DNA as a template; lane B is a blank
reverse transcription-PCR reaction performed without adding any RNA.
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Nested PCR specific for HCMV was performed on HHV-6-positive samples,
but no viral DNA was detected.
This report highlights two important observations: (i) HHV-6 exhibits
an in vivo tropism for aortic endothelium and (ii) HHV-6 can support a
low-level replication in aortic cells. The possibility that HHV-6 was
latent in the aortic tissue and reactivated upon in vitro cultivation
needs to be addressed via further experiments. However, these
observations show that aortic endothelium might represent an important
reservoir for viral reactivation and that it might be a significant
target for virus-induced injury.
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ACKNOWLEDGMENTS |
We acknowledge financial support from the Italian Ministry
of Health (AIDS Project) and from MURST.
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FOOTNOTES |
*
Phone: 39 0532 291408 Fax: 39 0532 247618 E-mail: dil{at}dns.unife.it
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Antonella Rotola
Dario Di Luca*
Enzo Cassai
Section of Microbiology
Department of Experimental and Diagnostic Medicine
University of Ferrara
Via Borsari 46
Ferrara, Italy
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| | | | |
Doris Ricotta
Alessandri Giulio
Adolfo Turano
Arnaldo Caruso
Institute of Microbiology
University of Brescia
Brescia, Italy
|
| | | | |
Claudio Muneretto
Section of Cardiac Surgery
University of Brescia
Brescia, Italy
|
Journal of Clinical Microbiology, August 2000, p. 3135-3136, Vol. 38, No. 8
0095-1137/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.
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