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Unravelling the Mysteries of Cytomegalovirus

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Immunology".

Deadline for manuscript submissions: closed (30 September 2021) | Viewed by 11508

Special Issue Editor

Faculty of Health Sciences, School of Pharmacy and Biomedical Sciences, Curtin University, Perth, Australia
Interests: CMV; NK cells; HCV; HIV; non tuberculous mycobacteria
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Most of us are CMV seropositive and have been so all our lives, but investigations of its impact have generated more questions than answers. Here are a few:

  • CMV induces novel populations of NK and gdT cells. What do these cells do?
  • CMV DNA is rarely detectable in the blood of healthy older people who have up to a third of their T-cells specific for its antigens. How does this happen and is it good for us?
  • CMV encodes homologues of human immune-related genes. These are not needed for viral replication so what do they do?
  • CMV causes pneumonitis in transplant recipients, retinitis in AIDS patients, and brain damage in babies – is it the same virus or is the host response different?
  • CMV replicates in the salivary gland and is shed in saliva, so how do some people remain seronegative? Have they never shared a spoon?

If you think you can answer one or more of these questions (or any others), then you may like to contribute to this Special Issue.

Assoc. Prof. Patricia Price
Guest Editor

Manuscript Submission Information

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Keywords

  • cytomegalovirus
  • CMV
  • saliva
  • diversity
  • endothelium
  • homologues of immune-related genes

Published Papers (3 papers)

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Research

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14 pages, 2496 KiB  
Article
Mapping and Characterization of HCMV-Specific Unconventional HLA-E-Restricted CD8 T Cell Populations and Associated NK and T Cell Responses Using HLA/Peptide Tetramers and Spectral Flow Cytometry
by Amélie Rousselière, Laurence Delbos, Céline Bressollette, Maïlys Berthaume and Béatrice Charreau
Int. J. Mol. Sci. 2022, 23(1), 263; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23010263 - 27 Dec 2021
Cited by 4 | Viewed by 2925
Abstract
HCMV drives complex and multiple cellular immune responses, which causes a persistent immune imprint in hosts. This study aimed to achieve both a quantitative determination of the frequency for various anti-HCMV immune cell subsets, including CD8 T, γδT, NK cells, and a qualitative [...] Read more.
HCMV drives complex and multiple cellular immune responses, which causes a persistent immune imprint in hosts. This study aimed to achieve both a quantitative determination of the frequency for various anti-HCMV immune cell subsets, including CD8 T, γδT, NK cells, and a qualitative analysis of their phenotype. To map the various anti-HCMV cellular responses, we used a combination of three HLApeptide tetramer complexes (HLA-EVMAPRTLIL, HLA-EVMAPRSLLL, and HLA-A2NLVPMVATV) and antibodies for 18 surface markers (CD3, CD4, CD8, CD16, CD19, CD45RA, CD56, CD57, CD158, NKG2A, NKG2C, CCR7, TCRγδ, TCRγδ2, CX3CR1, KLRG1, 2B4, and PD-1) in a 20-color spectral flow cytometry analysis. This immunostaining protocol was applied to PBMCs isolated from HCMV and HCMV+ individuals. Our workflow allows the efficient determination of events featuring HCMV infection such as CD4/CD8 ratio, CD8 inflation and differentiation, HCMV peptide-specific HLA-EUL40 and HLA-A2pp65CD8 T cells, and expansion of γδT and NK subsets including δ2γT and memory-like NKG2C+CD57+ NK cells. Each subset can be further characterized by the expression of 2B4, PD-1, KLRG1, CD45RA, CCR7, CD158, and NKG2A to achieve a fine-tuned mapping of HCMV immune responses. This assay should be useful for the analysis and monitoring of T-and NK cell responses to HCMV infection or vaccines. Full article
(This article belongs to the Special Issue Unravelling the Mysteries of Cytomegalovirus)
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Review

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19 pages, 433 KiB  
Review
A Review of Murine Cytomegalovirus as a Model for Human Cytomegalovirus Disease—Do Mice Lie?
by Michelle A. Fisher and Megan L. Lloyd
Int. J. Mol. Sci. 2021, 22(1), 214; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22010214 - 28 Dec 2020
Cited by 19 | Viewed by 4135
Abstract
Since murine cytomegalovirus (MCMV) was first described in 1954, it has been used to model human cytomegalovirus (HCMV) diseases. MCMV is a natural pathogen of mice that is present in wild mice populations and has been associated with diseases such as myocarditis. The [...] Read more.
Since murine cytomegalovirus (MCMV) was first described in 1954, it has been used to model human cytomegalovirus (HCMV) diseases. MCMV is a natural pathogen of mice that is present in wild mice populations and has been associated with diseases such as myocarditis. The species-specific nature of HCMV restricts most research to cell culture-based studies or to the investigation of non-invasive clinical samples, which may not be ideal for the study of disseminated disease. Initial MCMV research used a salivary gland-propagated virus administered via different routes of inoculation into a variety of mouse strains. This revealed that the genetic background of the laboratory mice affected the severity of disease and altered the extent of subsequent pathology. The advent of genetically modified mice and viruses has allowed new aspects of disease to be modeled and the opportunistic nature of HCMV infection to be confirmed. This review describes the different ways that MCMV has been used to model HCMV diseases and explores the continuing difficulty faced by researchers attempting to model HCMV congenital cytomegalovirus disease using the mouse model. Full article
(This article belongs to the Special Issue Unravelling the Mysteries of Cytomegalovirus)
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17 pages, 10388 KiB  
Review
Deciphering the Immunological Phenomenon of Adaptive Natural Killer (NK) Cells and Cytomegalovirus (CMV)
by Samantha Barnes, Ophelia Schilizzi, Katherine M. Audsley, Hannah V. Newnes and Bree Foley
Int. J. Mol. Sci. 2020, 21(22), 8864; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21228864 - 23 Nov 2020
Cited by 21 | Viewed by 3907
Abstract
Natural killer (NK) cells play a significant and vital role in the first line of defense against infection through their ability to target cells without prior sensitization. They also contribute significantly to the activation and recruitment of both innate and adaptive immune cells [...] Read more.
Natural killer (NK) cells play a significant and vital role in the first line of defense against infection through their ability to target cells without prior sensitization. They also contribute significantly to the activation and recruitment of both innate and adaptive immune cells through the production of a range of cytokines and chemokines. In the context of cytomegalovirus (CMV) infection, NK cells and CMV have co-evolved side by side to employ several mechanisms to evade one another. However, during this co-evolution the discovery of a subset of long-lived NK cells with enhanced effector potential, increased antibody-dependent responses and the potential to mediate immune memory has revolutionized the field of NK cell biology. The ability of a virus to imprint on the NK cell receptor repertoire resulting in the expansion of diverse, highly functional NK cells to this day remains a significant immunological phenomenon that only occurs in the context of CMV. Here we review our current understanding of the development of these NK cells, commonly referred to as adaptive NK cells and their current role in transplantation, infection, vaccination and cancer immunotherapy to decipher the complex role of CMV in dictating NK cell functional fate. Full article
(This article belongs to the Special Issue Unravelling the Mysteries of Cytomegalovirus)
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