The Role of the Virome in Health and Disease

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

Deadline for manuscript submissions: closed (20 October 2021) | Viewed by 19098

Special Issue Editor

Idorsia Pharmaceuticals Ltd., Hegenheimermattweg 91, 4123 Allschwil, Switzerland
Interests: viruses; virome; microbiome; phages; cancer; vaccines
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Viruses are the most abundant entities of the human microbiota. Yet, we still poorly understand their contribution to health and disease. High-throughput sequencing has recently revealed some characteristics of the virome of the intestine, the skin, the oral cavity, and other anatomical sites, but there is still little understanding of the impact of these viruses on the functioning of the microbial ecosystems.

The aim of this Special Issue is to shed light on some of the yet-unanswered questions regarding the human virome. For example, it is known that intestinal phage populations are expanded during inflammatory states such as IBD (Norman et al.; Cell 160; 447 [2015]). Yet, it remains unknown if this is characteristic of all inflammatory diseases and, most importantly, whether the expanded bacteriophages are causing the inflammation or are merely a consequence thereof. Moreover, there is evidence that transferring fecal bacteriophages from healthy donors can restore healthy intestinal microbiota in patients with recurrent Clostridioides difficile infection (e.g.; Ott et al.; Gastroenterology 152; 799-812 [2017]). These findings warrant a re-evaluation of the mode of action of fecal microbiota transplantation, traditionally thought to be mediated by transferred bacterial species, not phages.

Other topics and questions encouraged to be covered in this Special Issue include (but are not limited to): Are there small-animal models suitable to study the human virome (e.g., humanized mice with a human-like virome)? Can the viral dysbiosis observed in intestinal inflammation be recreated and studied in vitro? Can a given bacterial population exist in equilibrium with various different viromes and vice versa? Is analyzing the lung virome of animals and humans a suitable means to track the (zoonotic) transmission of respiratory viruses such as SARS-CoV-2? How can we further characterize the eukaryotic virome, as most of it is still “dark matter” (methodological papers are also welcome)? Are there certain members of the human virome (phages or eukaryotic viruses) that can serve as markers for disease? Are there ways to specifically manipulate the human virome to restore a “healthy” state in the case of dysbiosis (e.g., in IBD)? How can a “healthy” virome be defined given the high individual variability? What is the interplay between the virome and the (bacterial) microbiota in health and disease? There is a renewed interest in phage therapy for drug-resistant infection. Can virome analysis assist in the identification of potential therapeutic phages?

Dr. Felix Broecker
Guest Editor

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Keywords

  • virome
  • viromics
  • fecal microbiota transplantation
  • fecal virome transplantation
  • fecal filtrate transplantation
  • phage therapy
  • phageome
  • SARS-CoV-2
  • dysbiosis
  • metagenomics

Published Papers (6 papers)

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Editorial

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3 pages, 178 KiB  
Editorial
Editorial for the Special Issue: The Role of the Virome in Health and Disease
by Felix Broecker
Microorganisms 2022, 10(1), 20; https://doi.org/10.3390/microorganisms10010020 - 23 Dec 2021
Cited by 1 | Viewed by 1866
Abstract
Viruses are the most abundant biological entities on Earth, with an estimated total of 1031 virions [...] Full article
(This article belongs to the Special Issue The Role of the Virome in Health and Disease)

Research

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16 pages, 2342 KiB  
Article
Novel Siphoviridae Bacteriophages Infecting Bacteroides uniformis Contain Diversity Generating Retroelement
by Stina Hedžet, Maja Rupnik and Tomaž Accetto
Microorganisms 2021, 9(5), 892; https://doi.org/10.3390/microorganisms9050892 - 21 Apr 2021
Cited by 7 | Viewed by 3211
Abstract
Intestinal phages are abundant and important components of gut microbiota, yet the isolated and characterized representatives that infect abundant gut bacteria are sparse. Here we describe the isolation of human intestinal phages infecting Bacteroidesuniformis. Bacteroides is one of the most common [...] Read more.
Intestinal phages are abundant and important components of gut microbiota, yet the isolated and characterized representatives that infect abundant gut bacteria are sparse. Here we describe the isolation of human intestinal phages infecting Bacteroidesuniformis. Bacteroides is one of the most common bacterial groups in the global human gut microbiota; however, to date not many Bacteroides specific phages are known. Phages isolated in this study belong to a novel viral genus, Bacuni, within the Siphoviridae family. Their genomes encode diversity-generating retroelements (DGR), which were shown in other bacteriophages to promote phage adaptation to rapidly changing environmental conditions and to broaden their host range. Three isolated phages showed 99.83% genome identity but one of them infected a distinct B. uniformis strain. The tropism of Bacuni phages appeared to be dependent on the interplay of DGR mediated sequence variations of gene encoding putative phage fimbrial tip proteins and mutations in host genes coding for outer-membrane proteins. We found prophages with up to 85% amino acid similarity over two-thirds of the Bacuni phage genome in the B. acidifaciens and Prevotella sp. genomes. Despite the abundance of Bacteroides within the human microbiome, we found Bacuni phages only in a limited subset of published gut metagenomes. Full article
(This article belongs to the Special Issue The Role of the Virome in Health and Disease)
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12 pages, 4860 KiB  
Article
Human Endogenous Retroviruses in Glioblastoma Multiforme
by Zihao Yuan, Yuntao Yang, Ningyan Zhang, Claudio Soto, Xiaoqian Jiang, Zhiqiang An and Wenjin Jim Zheng
Microorganisms 2021, 9(4), 764; https://doi.org/10.3390/microorganisms9040764 - 06 Apr 2021
Cited by 11 | Viewed by 2460
Abstract
Glioblastoma multiforme (GBM) is the most aggressive and deadly brain tumor. It is primarily diagnosed in the elderly and has a 5-year survival rate of less than 6% even with the most aggressive therapies. The lack of biomarkers has made the development of [...] Read more.
Glioblastoma multiforme (GBM) is the most aggressive and deadly brain tumor. It is primarily diagnosed in the elderly and has a 5-year survival rate of less than 6% even with the most aggressive therapies. The lack of biomarkers has made the development of immunotherapy for GBM challenging. Human endogenous retroviruses (HERVs) are a group of viruses with long terminal repeat (LTR) elements, which are believed to be relics from ancient viral infections. Recent studies have found that those repetitive elements play important roles in regulating various biological processes. The differentially expressed LTR elements from HERVs are potential biomarkers for immunotherapy to treat GBM. However, the understanding of the LTR element expression in GBM is greatly lacking. Methods: We obtained 1077.4 GB of sequencing data from public databases. These data were generated from 111 GBM tissue studies, 30 GBM cell lines studies, and 45 normal brain tissues studies. We analyzed repetitive elements that were differentially expressed in GBM and normal brain samples. Results: We found that 48 LTR elements were differentially expressed (p-value < 0.05) between GBM and normal brain tissues, of which 46 were HERV elements. Among these 46 elements, 34 significantly changed HERVs belong to the ERV1 superfamily. Furthermore, 43 out of the 46 differentially expressed HERV elements were upregulated. Conclusion: Our results indicate significant differential expression of many HERV LTR elements in GBM and normal brain tissues. Expression levels of these elements could be developed as biomarkers for GBM treatments. Full article
(This article belongs to the Special Issue The Role of the Virome in Health and Disease)
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Review

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17 pages, 2096 KiB  
Review
The Roles of the Virome in Cancer
by Felix Broecker and Karin Moelling
Microorganisms 2021, 9(12), 2538; https://doi.org/10.3390/microorganisms9122538 - 08 Dec 2021
Cited by 9 | Viewed by 3567
Abstract
Viral infections as well as changes in the composition of the intestinal microbiota and virome have been linked to cancer. Moreover, the success of cancer immunotherapy with checkpoint inhibitors has been correlated with the intestinal microbial composition of patients. The transfer of feces—which [...] Read more.
Viral infections as well as changes in the composition of the intestinal microbiota and virome have been linked to cancer. Moreover, the success of cancer immunotherapy with checkpoint inhibitors has been correlated with the intestinal microbial composition of patients. The transfer of feces—which contain mainly bacteria and their viruses (phages)—from immunotherapy responders to non-responders, known as fecal microbiota transplantation (FMT), has been shown to be able to convert some non-responders to responders. Since phages may also increase the response to immunotherapy, for example by inducing T cells cross-reacting with cancer antigens, modulating phage populations may provide a new avenue to improve immunotherapy responsiveness. In this review, we summarize the current knowledge on the human virome and its links to cancer, and discuss the potential utility of bacteriophages in increasing the responder rate for cancer immunotherapy. Full article
(This article belongs to the Special Issue The Role of the Virome in Health and Disease)
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33 pages, 507 KiB  
Review
Towards the Forest Virome: High-Throughput Sequencing Drastically Expands Our Understanding on Virosphere in Temperate Forest Ecosystems
by Artemis Rumbou, Eeva J. Vainio and Carmen Büttner
Microorganisms 2021, 9(8), 1730; https://doi.org/10.3390/microorganisms9081730 - 14 Aug 2021
Cited by 15 | Viewed by 2960
Abstract
Thanks to the development of HTS technologies, a vast amount of genetic information on the virosphere of temperate forests has been gained in the last seven years. To estimate the qualitative/quantitative impact of HTS on forest virology, we have summarized viruses affecting major [...] Read more.
Thanks to the development of HTS technologies, a vast amount of genetic information on the virosphere of temperate forests has been gained in the last seven years. To estimate the qualitative/quantitative impact of HTS on forest virology, we have summarized viruses affecting major tree/shrub species and their fungal associates, including fungal plant pathogens, mutualists and saprotrophs. The contribution of HTS methods is extremely significant for forest virology. Reviewed data on viral presence in holobionts allowed us a first attempt to address the role of virome in holobionts. Forest health is dependent on the variability of microorganisms interacting with the host tree/holobiont; symbiotic microbiota and pathogens engage in a permanent interplay, which influences the host. Through virus–virus interplays synergistic or antagonistic relations may evolve, which may drastically affect the health of the holobiont. Novel insights of these interplays may allow practical applications for forest plant protection based on endophytes and mycovirus biocontrol agents. The current analysis is conceived in light of the prospect that novel viruses may initiate an emergent infectious disease and that measures for the avoidance of future outbreaks in forests should be considered. Full article
(This article belongs to the Special Issue The Role of the Virome in Health and Disease)
15 pages, 336 KiB  
Review
The Presence of Bacteriophages in the Human Body: Good, Bad or Neutral?
by Marzanna Łusiak-Szelachowska, Beata Weber-Dąbrowska, Maciej Żaczek, Jan Borysowski and Andrzej Górski
Microorganisms 2020, 8(12), 2012; https://doi.org/10.3390/microorganisms8122012 - 16 Dec 2020
Cited by 15 | Viewed by 3933
Abstract
The presence of bacteriophages (phages) in the human body may impact bacterial microbiota and modulate immunity. The role of phages in human microbiome studies and diseases is poorly understood. However, the correlation between a greater abundance of phages in the gut in ulcerative [...] Read more.
The presence of bacteriophages (phages) in the human body may impact bacterial microbiota and modulate immunity. The role of phages in human microbiome studies and diseases is poorly understood. However, the correlation between a greater abundance of phages in the gut in ulcerative colitis and diabetes has been suggested. Furthermore, most phages found at different sites in the human body are temperate, so their therapeutic effects and their potential beneficial effects remain unclear. Hence, far, no correlation has been observed between the presence of widespread crAssphage in the human population and human health and diseases. Here, we emphasize the beneficial effects of phage transfer in fecal microbiota transplantation (FMT) in Clostridioides difficile infection. The safety of phage use in gastrointestinal disorders has been demonstrated in clinical studies. The significance of phages in the FMT as well as in gastrointestinal disorders remains to be established. An explanation of the multifaceted role of endogenous phages for the development of phage therapy is required. Full article
(This article belongs to the Special Issue The Role of the Virome in Health and Disease)
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