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      The mysterious anelloviruses: investigating its role in human diseases

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          Abstract

          Anelloviruses (AVs) that infect the human population are members of the Anelloviridae family. They are widely distributed in human populations worldwide. Torque teno virus (TTV) was the first virus of this family to be identified and is estimated to be found in the serum of 80–90% of the human population. Sometime after the identification of TTV, Torque teno mini virus (TTMV) and Torque teno midi virus (TTMDV) were also identified and classified in this family. Since identifying these viruses, have been detected in various types of biological fluids of the human body, including blood and urine, as well as vital organs such as the liver and kidney. They can be transmitted from person to person through blood transfusions, fecal-oral contact, and possibly sexual intercourse. Recent studies on these newly introduced viruses show that although they are not directly related to human disease, they may be indirectly involved in initiating or exacerbating some human population-related diseases and viral infections. Among these diseases, we can mention various types of cancers, immune system diseases, viral infections, hepatitis, and AIDS. Also, they likely use the microRNAs (miRNAs) they encode to fulfill this cooperative role. Also, in recent years, the role of proliferation and their viral load, especially TTV, has been highlighted to indicate the immune system status of immunocompromised people or people who undergo organ transplants. Here, we review the possible role of these viruses in diseases that target humans and highlight them as important viruses that require further study. This review can provide new insights to researchers.

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          Most cited references159

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          Redefining chronic viral infection.

          Viruses that cause chronic infection constitute a stable but little-recognized part of our metagenome: our virome. Ongoing immune responses hold these chronic viruses at bay while avoiding immunopathologic damage to persistently infected tissues. The immunologic imprint generated by these responses to our virome defines the normal immune system. The resulting dynamic but metastable equilibrium between the virome and the host can be dangerous, benign, or even symbiotic. These concepts require that we reformulate how we assign etiologies for diseases, especially those with a chronic inflammatory component, as well as how we design and interpret genome-wide association studies, and how we vaccinate to limit or control our virome.
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            CpG motifs in bacterial DNA and their immune effects.

            Unmethylated CpG motifs are prevalent in bacterial but not vertebrate genomic DNAs. Oligodeoxynucleotides (ODN) containing CpG motifs activate host defense mechanisms leading to innate and acquired immune responses. The recognition of CpG motifs requires Toll-like receptor (TLR) 9, which triggers alterations in cellular redox balance and the induction of cell signaling pathways including the mitogen activated protein kinases (MAPKs) and NF kappa B. Cells that express TLR-9, which include plasmacytoid dendritic cells (PDCs) and B cells, produce Th1-like proinflammatory cytokines, interferons, and chemokines. Certain CpG motifs (CpG-A) are especially potent at activating NK cells and inducing IFN-alpha production by PDCs, while other motifs (CpG-B) are especially potent B cell activators. CpG-induced activation of innate immunity protects against lethal challenge with a wide variety of pathogens, and has therapeutic activity in murine models of cancer and allergy. CpG ODN also enhance the development of acquired immune responses for prophylactic and therapeutic vaccination.
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              Human anelloviruses: an update of molecular, epidemiological and clinical aspects.

              Human torque teno viruses (TTVs) are new, emerging infectious agents, recently assigned to the family Anelloviridae. The first representative of the genus, torque teno virus (TTV), was discovered in 1997, followed by torque teno mini virus (TTMV) in 2000, and torque teno midi virus (TTMDV) in 2007. These viruses are characterized by an extremely high prevalence, with relatively uniform distribution worldwide and a high level of genomic heterogeneity, as well as an apparent pan-tropism at the host level. Although these viruses have a very high prevalence in the general population across the globe, neither their interaction with their hosts nor their direct involvement in the etiology of specific diseases are fully understood. Since their discovery, human anelloviruses, and especially TTV, have been suggested to be associated with various diseases, such as hepatitis, respiratory diseases, cancer, hematological and autoimmune disorders, with few arguments for their direct involvement. Recent studies have started to reveal interactions between TTVs and the host's immune system, leading to new hypotheses for potential pathological mechanisms of these viruses. In this review article, we discuss the most important aspects and current status of human TTVs in order to guide future studies.
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                Author and article information

                Contributors
                poortahmasebiv@tbzmed.ac.ir
                Journal
                BMC Microbiol
                BMC Microbiol
                BMC Microbiology
                BioMed Central (London )
                1471-2180
                29 January 2024
                29 January 2024
                2024
                : 24
                : 40
                Affiliations
                [1 ]Department of Bacteriology and Virology, Faculty of Medicine, Tabriz University of Medical Sciences, ( https://ror.org/04krpx645) Tabriz, Iran
                [2 ]Research Center for Clinical Virology, Tehran University of Medical Sciences, ( https://ror.org/01c4pz451) Tehran, Iran
                [3 ]Department of Pathology, Faculty of Medicine, Tabriz University of Medical Sciences, ( https://ror.org/04krpx645) Tabriz, Iran
                [4 ]Research Center of Pediatric Infectious Diseases, Institute of Immunology and Infectious Diseases, Iran University of Medical Sciences, ( https://ror.org/03w04rv71) Tehran, Iran
                Article
                3187
                10.1186/s12866-024-03187-7
                10823751
                38281930
                774107b1-640a-4f24-9684-abb8c65d72e5
                © The Author(s) 2024

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

                History
                : 14 November 2023
                : 8 January 2024
                Categories
                Review
                Custom metadata
                © BioMed Central Ltd., part of Springer Nature 2024

                Microbiology & Virology
                anellovirus,torque teno virus,viral infection,coinfection,microrna
                Microbiology & Virology
                anellovirus, torque teno virus, viral infection, coinfection, microrna

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