Cytomegalovirus Infection Causes an Increase of Arterial Blood Pressure
Open accessAbstract
Cytomegalovirus (CMV) infection is a common infection in adults (seropositive 60-99% globally), and is associated with cardiovascular diseases, in line with risk factors such as hypertension and atherosclerosis. Several viral infections are linked to hypertension, including human herpes virus 8 (HHV-8) and HIV-1. The mechanisms of how viral infection contributes to hypertension or increased blood pressure are not defined. In this report, the role of CMV infection as a cause of increased blood pressure and in forming aortic atherosclerotic plaques is examined. Using in vivo mouse model and in vitro molecular biology analyses, we find that CMV infection alone caused a significant increase in arterial blood pressure (ABp) (p<0.01 approximately 0.05), measured by microtip catheter technique. This increase in blood pressure by mouse CMV (MCMV) was independent of atherosclerotic plaque formation in the aorta, defined by histological analyses. MCMV DNA was detected in blood vessel samples of viral infected mice but not in the control mice by nested PCR assay. MCMV significantly increased expression of pro-inflammatory cytokines IL-6, TNF-alpha, and MCP-1 in mouse serum by enzyme-linked immunosorbent assay (ELISA). Using quantitative real time reverse transcriptase PCR (Q-RT-PCR) and Western blot, we find that CMV stimulated expression of renin in mouse and human cells in an infectious dose-dependent manner. Co-staining and immunofluorescent microscopy analyses showed that MCMV infection stimulated renin expression at a single cell level. Further examination of angiotensin-II (Ang II) in mouse serum and arterial tissues with ELISA showed an increased expression of Ang II by MCMV infection. Consistent with the findings of the mouse trial, human CMV (HCMV) infection of blood vessel endothelial cells (EC) induced renin expression in a non-lytic infection manner. Viral replication kinetics and plaque formation assay showed that an active, CMV persistent infection in EC and expression of viral genes might underpin the molecular mechanism. These results show that CMV infection is a risk factor for increased arterial blood pressure, and is a co-factor in aortic atherosclerosis. Viral persistent infection of EC may underlie the mechanism. Control of CMV infection can be developed to restrict hypertension and atherosclerosis in the cardiovascular system.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Acute infectious disease leads to upregulation of the RAAS system in a mouse model of cytomegalovirus infection.
“Acute infectious disease leads to upregulation of the RAAS system in a mouse model of cytomegalovirus infection [141].”
From Interaction of the endocrine system with inflammation: a function of energy and volume regulation (2014) · cites this paper as [141]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Morphology, physiology, and molecular biology of renin secretion
Hackenthal, E., Paul, M., Ganten, D., & Taugner, R. (1990) · Physiological Reviews · doi:10.1152/physrev.1990.70.4.1067 · Cited by 614 · see citing works
Zhou, Y. F., Leon, M. B., Waclawiw, M. A., Popma, J. J., Yu, Z., Finkel, T., & Epstein, S. E. (1996) · New England Journal of Medicine · doi:10.1056/nejm199608293350903 · Cited by 450 · see citing works
Expression of Human Herpesvirus 8 in Primary Pulmonary Hypertension
Cool, C. D., Rai, P. R., Yeager, M. E., Hernández-Saavedra, D., Serls, A. E., Bull, T., Geraci, M. W., Brown, K. M., Routes, J. M., Tuder, R. M., et al. (2003) · New England Journal of Medicine · doi:10.1056/nejmoa035115 · Cited by 292 · see citing works
Valantine, H. A., Gao, S., Menon, S. G., Renlund, D. G., Hunt, S. A., Oyer, P. E., Stinson, E. B., Brown, B. W., Merigan, T. C., & SCHROEDER, J. S. (1999) · Circulation · doi:10.1161/01.cir.100.1.61 · Cited by 291 · see citing works
Sriramula, S., Haque, M., Majid, D. S. A., & Francis, J. (2008) · Hypertension · doi:10.1161/hypertensionaha.107.102152 · Cited by 279 · see citing works
Pulmonary arterial remodeling induced by a Th2 immune response
Daley, E., Emson, C. L., Guignabert, C., Malefyt, R. D. W., Louten, J., Kurup, V. P., Hogaboam, C. M., Taraseviciene‐Stewart, L., Voelkel, N. F., Rabinovitch, M., et al. (2008) · The Journal of Experimental Medicine · doi:10.1084/jem.20071008 · Cited by 253 · see citing works
Serum Uric Acid Predicts Incident Hypertension in a Biethnic Cohort
Mellen, P. B., Bleyer, A. J., Erlinger, T. P., Evans, G. W., Nieto, F. J., Wagenknecht, L. E., Wofford, M. R., & Herrington, D. M. (2006) · Hypertension · doi:10.1161/01.hyp.0000249768.26560.66 · Cited by 234 · see citing works
Grundy, J. E., Lawson, K. M., MacCormac, L. P., et al. (1998) · The Journal of Infectious Diseases · doi:10.1086/515300 · Cited by 201 · see citing works
Sipahi, İ., Tuzcu, E. M., Schoenhagen, P., Wolski, K. E., Nicholls, S. J., Balog, C., Crowe, T. D., & Nissen, S. E. (2006) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2006.05.045 · Cited by 198 · see citing works
Su, T.-C., Jeng, J.-S., Chien, K.-L., Sung, F.-C., Hsu, H.-C., & Lee, Y.-T. (2001) · Stroke · doi:10.1161/str.32.10.2265 · Cited by 158 · see citing works
Landry, M. L., Stanat, S. C., Biron, K. K., et al. (2000) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.44.3.688-692.2000 · Cited by 152 · see citing works
Smieja, M., Gnarpe, J. A., Lonn, E., Gnarpe, H., Olsson, G. O., Yi, Q., Džavík, V., McQueen, M., & Yusuf, S. (2003) · Circulation · doi:10.1161/01.cir.0000044940.65226.1f · Cited by 149 · see citing works
Cytomegalovirus infection increases development of atherosclerosis in Apolipoprotein-E knockout mice
Hsich, E., Zhou, Y. F., Paigen, B. J., Johnson, T. M., Burnett, M. S., & Epstein, S. E. (2001) · Atherosclerosis · doi:10.1016/s0021-9150(00)00608-0 · Cited by 146 · see citing works
Coles, B., Fielding, C., Rose-John, S., Scheller, J., Jones, S. A., & O'Donnell, V. (2007) · American Journal of Pathology · doi:10.2353/ajpath.2007.061078 · Cited by 143 · see citing works
Human Cytomegalovirus Persistently Infects Aortic Endothelial Cells
Fish, K. N., Söderberg‐Nauclér, C., Mills, L. K., Stenglein, S., & Nelson, J. A. (1998) · Journal of Virology · doi:10.1128/jvi.72.7.5661-5668.1998 · Cited by 139 · see citing works
Sachetelli, S., Liu, Q., Zhang, S.-L., et al. (2006) · Kidney International · doi:10.1038/sj.ki.5000210 · Cited by 131 · see citing works
Cellular Localization of Latent Murine Cytomegalovirus
Koffron, A. J., Hummel, M., Patterson, B. K., Yan, S., Kaufman, D. B., Fryer, J. P., Stuart, F. P., & Abecassis, M. I. (1998) · Journal of Virology · doi:10.1128/jvi.72.1.95-103.1998 · Cited by 129 · see citing works
Ahn, J.-H., & Hayward, G. S. (2000) · Virology · doi:10.1006/viro.2000.0448 · Cited by 128 · see citing works
Human Cytomegalovirus Seropositivity Is Associated With Impaired Vascular Function
Grahame-Clarke, C. N., Chan, N. N., Andrew, D., Ridgway, G. L., Betteridge, D. J., Emery, V. C., Colhoun, H. M., & Vallance, P. J. (2003) · Circulation · doi:10.1161/01.cir.0000084505.54603.c7 · Cited by 118 · see citing works
RAS inhibition in hypertension
Ibrahim, M. M. (2006) · Journal of Human Hypertension · doi:10.1038/sj.jhh.1001960 · Cited by 114 · see citing works
Cytomegalovirus Infection of the Heart Is Common in Patients with Fatal Myocarditis
Kytö, V., Vuorinen, T., Saukko, P. J., et al. (2005) · Clinical Infectious Diseases · doi:10.1086/427804 · Cited by 113 · see citing works
Detection of Human Cytomegalovirus DNA, RNA, and Antibody in Normal Donor Blood
Zhang, L. J., Hanff, P. A., Rutherford, C., Churchill, W. H., & Crumpacker, C. S. (1995) · The Journal of Infectious Diseases · doi:10.1093/infdis/171.4.1002 · Cited by 108 · see citing works
Self-citationHistorical Perspective of the Renin-Angiotensin System
Hall, J. E. (2003) · Molecular Biotechnology · doi:10.1385/mb:24:1:27 · Cited by 103 · see citing works
Adler, S. P., Hur, J. K., Wang, J. B., et al. (1998) · The Journal of Infectious Diseases · doi:10.1086/517355 · Cited by 91 · see citing works
Increased mortality in long-term intensive care patients with active cytomegalovirus infection*
Ziemann, M., Sedemund‐Adib, B., Reiland, P., et al. (2008) · Critical Care Medicine · doi:10.1097/ccm.0b013e31818f3fc4 · Cited by 87 · see citing works
High-Fat Diet Elevates Blood Pressure and Cerebrovascular Muscle Ca 2+ Current
Wilde, D. W., Massey, K., Walker, G. K., et al. (2000) · Hypertension · doi:10.1161/01.hyp.35.3.832 · Cited by 79 · see citing works
Stassen, F. R. M., Vega-Córdova, X., Vliegen, I., & Bruggeman, C. A. (2006) · Journal of Clinical Virology · doi:10.1016/j.jcv.2005.11.007 · Cited by 76 · see citing works
Inflammation, Malnutrition and Atherosclerosis in End-Stage Renal Disease: A Global Perspective
do Nascimento, M. M., Pecoits‐Filho, R., Lindholm, B., et al. (2002) · Blood Purification · doi:10.1159/000063559 · Cited by 67 · see citing works
Lurain, N. S., Fox, A. M., Lichy, H. M., et al. (2006) · Virology Journal · doi:10.1186/1743-422x-3-4 · Cited by 55 · see citing works
Enhanced Cytomegalovirus Infection in Atherosclerotic Human Blood Vessels
Nerheim, P., Meier, J. L., Vasef, M. A., Li, W.-G., Hu, L., Rice, J. B., Gavrila, D., Richenbacher, W. E., & Weintraub, N. L. (2004) · American Journal Of Pathology · doi:10.1016/s0002-9440(10)63148-3 · Cited by 55 · see citing works
Daus, H., Özbek, C., Saage, D., et al. (1998) · Cardiology · doi:10.1159/000006824 · Cited by 45 · see citing works
Embryonic stem cells cultured in biodegradable scaffold repair infarcted myocardium in mice.
Ke, Q., Yang, Y., Rana, J. S., et al. (2005) · PubMed · Cited by 43 · see citing works
Self-citationChen, Y., Ke, Q., Xiao, Y., et al. (2005) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00822.2004 · Cited by 39 · see citing works
Self-citationWeiss, J. R. (1995) · Archives of Internal Medicine · doi:10.1001/archinte.155.21.2350 · Cited by 33 · see citing works
Herpesvirus infection: an overview of the clinical manifestations.
Peterslund, N. A. (1991) · PubMed · Cited by 29 · see citing works
Gerna, G., Percivalle, E., Sarasini, A., et al. (2002) · Journal of Clinical Microbiology · doi:10.1128/jcm.40.1.233-238.2002 · Cited by 29 · see citing works
Comparison of coronary and aortic atherosclerosis in youth from Japan and the USA
Takei, H., Strong, J. P., Yutani, C., & Malcom, G. T. (2005) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2004.11.014 · Cited by 25 · see citing works
Manhiani, M. M., Quigley, J. E., Socha, M. J., et al. (2007) · Kidney & Blood Pressure Research · doi:10.1159/000104094 · Cited by 24 · see citing works
Blok, M. J., Lautenschlager, I., Goossens, V. J., et al. (2000) · Journal of Clinical Microbiology · doi:10.1128/jcm.38.12.4485-4491.2000 · Cited by 23 · see citing works
Atherosclerosis of the Carotid Artery
Saetta, A. A., Fanourakis, G., Agapitos, E., et al. (2000) · Cardiovascular Pathology · doi:10.1016/s1054-8807(00)00040-5 · Cited by 22 · see citing works
Roy, V., Prabhakar, S., Pulvirenti, J., et al. (1999) · PubMed · Cited by 18 · see citing works
National Eye Institute issues clinical alert about CMV retinitis in AIDS
Marwick, C. (1991) · JAMA · doi:10.1001/jama.266.19.2665 · Cited by 1 · see citing works
Flagged first, then by citations
Research works printed but not linked: 1
- [1]Pass RF 2001 Cytomegalovirus. Knipe DM Howley PM Fields Virology New York Lippincott Williams & Wilkins. Vol. 2 2675 730
Cited by
Sorted by citations
Redefining Chronic Viral Infection
Virgin, H. W., Wherry, E. J., & Ahmed, R. (2009) · Cell · doi:10.1016/j.cell.2009.06.036 · Cited by 1,031 · see citing works
Gain and loss of T cell subsets in old age: age-related reshaping of the T cell repertoire.
Arnold, C. R., Wolf, J., Brunner, S., Herndler-Brandstetter, D., & Grubeck-Loebenstein, B. (2011) · Journal of Clinical Immunology · doi:10.1007/s10875-010-9499-x · Cited by 170 · see citing works
. Persistent viral infections and immune aging.
Brunner, S., Herndler-Brandstetter, D., Weinberger, B., & Grubeck-Loebenstein, B. (2011) · Ageing Research Reviews · doi:10.1016/j.arr.2010.08.003 · Cited by 143 · see citing works
Interaction of the endocrine system with inflammation: a function of energy and volume regulation
Straub, R. H. (2014) · Arthritis Research & Therapy · doi:10.1186/ar4484 · Cited by 121 · see citing works
“tion [141].”
Broadley, I., Pera, A., Morrow, G., Davies, K. A., & Kern, F. (2017) · Frontiers in Immunology · doi:10.3389/fimmu.2017.00195 · Cited by 103 · see citing works
- Authors
- Cheng, J., Ke, Q., Jin, Z., Wang, H., Kocher, O., Morgan, J. P., Zhang, J., & Crumpacker, C. S.
- Affiliations
- Beth Israel Deaconess Medical Center (US)
- Tufts University (US)
- Corresponding author
- Zhang, Jielin
- Crumpacker, Clyde S.
- Venue
- PLoS Pathogens
- Publisher
- Public Library of Science (PLoS)
- Published
- 2009-05-15
- Volume
- 5
- Issue
- 5
- Pages
- e1000427
- ISSN
- 1553-7366 (ISSN-L)
- 1553-7374
- PMC
- PMC2673691
- OpenAlex
- W2109392578
- Cited by
- 163
- References
- 42
- Citations by year
- 2026: 4 · 2025: 6 · 2024: 7 · 2023: 7 · 2022: 8 · 2021: 10 · 2020: 13 · 2019: 7 · 2018: 7 · 2017: 9 · 2016: 9 · 2015: 14 · 2014: 11 · 2013: 11 · 2012: 14
- FWCI
- 8.99
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- PLoS Pathogens (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Digital Access to Scholarship at Harvard (DASH) (Harvard University) (submittedVersion, cc-by)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Figshare (submittedVersion, cc-by)
- Funders
- China Scholarship Council
- National Institutes of Health
- National Heart, Lung, and Blood Institute (R01HL071859, HL71859)
- National Institute of Allergy and Infectious Diseases (K18AI055313)
- Topics
- Health Sciences › Medicine › Epidemiology › Cytomegalovirus and herpesvirus research
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Renin-Angiotensin System Studies
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Blood Pressure and Hypertension Studies
- Keywords
- cytomegalovirus infection, hypertension, arterial blood pressure, murine cytomegalovirus, human cytomegalovirus, aortic atherosclerosis, renin expression, angiotensin II, endothelial cells, inflammatory cytokines, cardiovascular risk factors
- MeSH terms
- Angiotensin II, Animals, Aorta, Blood Pressure, Blood Vessels, Cell Line, Cytomegalovirus Infections, Diet, Atherogenic, Disease Models, Animal, DNA, Viral, Enzyme-Linked Immunosorbent Assay, Herpesviridae Infections, Humans, Mice, Inbred C57BL, Models, Biological, Renin, RNA, Viral, Virus Replication, Chi-Square Distribution, Polymerase Chain Reaction, Cytokines, Muromegalovirus, Atherosclerosis, Mice
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
