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Cytomegalovirus, Inflammation and Oncomodulation

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A special issue of Microorganisms (ISSN 2076-2607). This special issue belongs to the section "Molecular Microbiology and Immunology".

Deadline for manuscript submissions: closed (31 May 2021) | Viewed by 11931

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Special Issue Editor

Dr. Afsar Rahbar

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Guest Editor

Department of Medicine, Karolinska Institutet, BioClinicum:J5:30, Akademiska Stråket 1, Karolinska Institutet, 17164 Solna, Sweden
Interests: immunology; infection; cytomegalovirus; human cytomegalovirus; oncogene viruses in cancer

Special Issue Information

Dear Colleagues,

Human cytomegalovirus (HCMV) is an immune and onco-modulatory virus that belongs to the herpes virus family with unique capacity to maintain latency after primary infection. The sero-prevalence for HCMV is 50–100% worldwide. Inflammation is the key element for HCMV reactivation in blood monocytes that result in differentiation of monocytes into macrophages or dendritic cells, which can transmit the virus to other cell types and can cause serious disease in immunocompromised individuals and cancer patients. In fact, HCMV infection results in increased expression of COX-2 and 5-LO expression, production of prostaglandins and leukotrienes, and pro-inflammatory cytokines (e.g. IL-1, IL-6, IL-8 MCP-1, RANTES, MIP-1α, TNF-α, and IFN-g). Effects of active or latent HCMV infection have been proposed to contribute to the inflammatory process in patients with different autoimmune diseases, such as inflammatory bowel diseases, dermatomyositis, Rheumatoid Arthritis, and systemic sclerosis. Furthermore, inflammation in the tumor micro-environment is strongly linked to tumor development and is a hallmark of cancer. During the past years a link between HCMV and certain types of cancer such as Glioblastoma, breast cancer, ovarian cancer and colon cancer has been shown. In these studies high prevalence of viral proteins and nucleic acids was detected in tumor tissue specimens with evidence of onco-modulatory abilities conferred by this virus. Frequent reactivation of latent HCMV in tumor tissues by inflammation would exacerbate inflammation by increasing production of inflammatory factors that may contribute to tumor progression.

Assoc. Prof. Dr. Afsar Rahbar
Guest Editor

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Keywords

Human cytomegalovirus
Autoimmune diseases
Cancer
Inflammation

Published Papers (4 papers)

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Research

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15 pages, 4719 KiB

Open AccessArticle

Human Cytomegalovirus Reduces Endothelin-1 Expression in Both Endothelial and Vascular Smooth Muscle Cells

by Koon-Chu Yaiw, Abdul-Aleem Mohammad, Chato Taher, Huanhuan Leah Cui, Helena Costa, Ourania N. Kostopoulou, Masany Jung, Alice Assinger, Vanessa Wilhelmi, Jiangning Yang, Klas Strååt, Afsar Rahbar, John Pernow and Cecilia Söderberg-Nauclér

Microorganisms 2021, 9(6), 1137; https://0-doi-org.brum.beds.ac.uk/10.3390/microorganisms9061137 - 25 May 2021

Cited by 4 | Viewed by 2309

Abstract

Human cytomegalovirus (HCMV) is an opportunistic pathogen that has been implicated in the pathogenesis of atherosclerosis. Endothelin-1 (ET-1), a potent vasoconstrictive peptide, is overexpressed and strongly associated with many vasculopathies. The main objective of this study was to investigate whether HCMV could affect ET-1 production. As such, both endothelial and smooth muscle cells, two primary cell types involved in the pathogenesis of atherosclerosis, were infected with HCMV in vitro and ET-1 mRNA and proteins were assessed by quantitative PCR assay, immunofluorescence staining and ELISA. HCMV infection significantly decreased ET-1 mRNA and secreted bioactive ET-1 levels from both cell types and promoted accumulation of the ET-1 precursor protein in infected endothelial cells. This was associated with inhibition of expression of the endothelin converting enzyme-1 (ECE-1), which cleaves the ET-1 precursor protein to mature ET-1. Ganciclovir treatment did not prevent the virus suppressive effects on ET-1 expression. Consistent with this observation we identified that the IE2-p86 protein predominantly modulated ET-1 expression. Whether the pronounced effects of HCMV in reducing ET-1 expression in vitro may lead to consequences for regulation of the vascular tone in vivo remains to be proven. Full article

(This article belongs to the Special Issue Cytomegalovirus, Inflammation and Oncomodulation)

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11 pages, 1141 KiB

Open AccessArticle

Clinical Characteristics Associated with the Development of Cystoid Macular Edema in Patients with Cytomegalovirus Retinitis

by Hye-Ji Kwon, Gisung Son, Joo-Yong Lee, June-Gone Kim and Yoon-Jeon Kim

Microorganisms 2021, 9(6), 1114; https://0-doi-org.brum.beds.ac.uk/10.3390/microorganisms9061114 - 21 May 2021

Cited by 4 | Viewed by 1673

Abstract

We evaluated the incidence and characteristics of eyes with cytomegalovirus (CMV) retinitis according to the occurrence of cystoid macular edema (CME) and identified the risk factors of its occurrence. Patients diagnosed with CMV retinitis and examined using optical coherence tomography were classified according to the development of CME. The CME group was further divided according to the presence of active retinitis at the time of CME development. The demographics, serologic findings, ophthalmic presentations, ocular treatments, and visual prognosis were compared. CME was identified in 25 eyes (17 eyes with active retinitis and 8 eyes with inactive retinitis) out of the 67 eyes with CMV retinitis. Visual acuity was worse in the CME group than in the non-CME group. The CME group had longer CMV viremia duration, zone 1 involvement, and larger extent of CMV retinitis. While CME with concurrent active retinitis developed in eyes with direct foveal involvement of retinitis in the acute phase and required more ganciclovir injections after CME development, CME without active retinitis developed in eyes with larger extents of involvement and more intravitreal ganciclovir injections before CME development. Zone 1 involvement and longer CMV viremia duration were independently associated with the occurrence of CME. CME, which caused visual deterioration, developed in considerable patients with CMV retinitis and had different characteristics according to the presence of active retinitis. Full article

(This article belongs to the Special Issue Cytomegalovirus, Inflammation and Oncomodulation)

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16 pages, 3147 KiB

Open AccessArticle

Detection of Human Cytomegalovirus Proteins in Paraffin-Embedded Breast Cancer Tissue Specimens—A Novel, Automated Immunohistochemical Staining Protocol

by Joel Touma, Yan Liu, Afsar Rahbar, Mattia Russel Pantalone, Nerea Martin Almazan, Katja Vetvik, Cecilia Söderberg-Nauclér, Jürgen Geisler and Torill Sauer

Microorganisms 2021, 9(5), 1059; https://0-doi-org.brum.beds.ac.uk/10.3390/microorganisms9051059 - 13 May 2021

Cited by 7 | Viewed by 3407

Abstract

Emerging evidence supports a significant association between human cytomegalovirus (HCMV) and human malignancies, suggesting HCMV as a human oncomodulatory virus. HCMV gene products are found in >90% of breast cancer tumors and seem to be correlated with more aggressive disease. The definitive diagnosis of HCMV relies on identification of virus inclusions and/or viral proteins by different techniques including immunohistochemical staining. In order to reduce biases and improve clinical value of HCMV diagnostics in oncological pathology, automation of the procedure is needed and this was the purpose of this study. Tumor specimens from 115 patients treated for primary breast cancer at Akershus University Hospital in Norway were available for the validation of the staining method in this retrospective study. We demonstrate that our method is highly sensitive and delivers excellent reproducibility for staining of HCMV late antigen (LA), which makes this method useful for future routine diagnostics and scientific applications. Full article

(This article belongs to the Special Issue Cytomegalovirus, Inflammation and Oncomodulation)

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Review

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12 pages, 615 KiB

Open AccessReview

The Impact of Human Herpesviruses in Clinical Practice of Inflammatory Bowel Disease in the Era of COVID-19

by Shuhei Hosomi, Yu Nishida and Yasuhiro Fujiwara

Microorganisms 2021, 9(9), 1870; https://0-doi-org.brum.beds.ac.uk/10.3390/microorganisms9091870 - 03 Sep 2021

Cited by 8 | Viewed by 3772

Abstract

Human herpesviruses (HHVs): herpes simplex virus (HSV) types 1 (HSV-1) and 2 (HSV-2), varicella-zoster virus (VZV), Epstein-Barr virus (EBV), cytomegalovirus (CMV), HHV-6, HHV-7, and HHV-8, are known to be part of a family of DNA viruses that cause several diseases in humans. In clinical practice of inflammatory bowel disease (IBD), the complication of CMV enterocolitis, which is caused by CMV reactivation under disruption of intestinal barrier function, inflammation, or strong immunosuppressive therapy, is well known to affect the prognosis of disease. However, the relationship between other HHVs and IBD remains unclear. In the transplantation field, reactivation of other viruses, such as HHV-6, could cause colitis under immunosuppressed condition. Recent research revealed that combined infection of some HHVs could be a risk factor for colectomy in patients with ulcerative colitis. This suggests that it would be important to clarify HHV behavior in the treatment for patients with IBD, especially in those under immunosuppressive therapies. Looking at the relationship with recently emerged novel coronaviruses (SARS-CoV-2), there are reports describe that SARS-CoV-2 might induce reactivation of HSV-1, EBV, VZV (herpes zoster), and HHV-6/7. If SARS-CoV-2 infection becomes common, vigilance against HHV reactivation may become more crucial. In this review, we discuss the impact of HHVs in clinical practice of inflammatory bowel diseases, especially during the SARS-CoV-2 pandemic. Full article

(This article belongs to the Special Issue Cytomegalovirus, Inflammation and Oncomodulation)

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