Advancing Research of Anelloviruses, Second Edition

A special issue of Viruses (ISSN 1999-4915). This special issue belongs to the section "Human Virology and Viral Diseases".

Deadline for manuscript submissions: closed (30 June 2026) | Viewed by 4545

Editors


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Guest Editor
Laboratory of Virology, National Institute for Infectious Diseases Lazzaro Spallanzani, Rome, Italy
Interests: anelloviruses; virome; SARS-CoV-2; next-generation sequencing
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Special Issue Information

Dear Colleagues,

Following the success of the Special Issue “Advancing Research of Anelloviruses” (see here), we are editing a second edition of this very popular topic and accepting new submissions.

Anelloviruses (AVs) are a vast group of agents discovered in recent years that may infect humans and various animal species. The first indication of their existence was in 1997, when Japanese scientists, using representational difference analysis for examining the blood of patients with cryptogenetic post-transfusion hepatitis, detected a novel virus with a particularly small genome formed by a circular single-stranded DNA of negative polarity. This new virus was named TT virus (TTV) after the initials of the first patient in whom it was identified, but its extended name was changed in 2004 to Torquetenovirus (from the Latin words torques and tenuis, meaning necklace and thin, respectively) to maintain the original acronym and conform to the International Committee on Taxonomy of Viruses rule that no official virus designation should be derived from people’s names. The discovery of TTV soon opened a Pandora’s box of new viruses. In fact, it was followed, in the year 2000 by the detection in diseased and healthy individuals of numerous related, previously unrecognized viruses with genome properties clearly similar to those of TTV, although often very genetically divergent from it. Furthermore, PCR testing of some blood donors for TTV produced shorter amplicons than expected if the virus amplified was truly TTV, and further characterization revealed the existence of additional viruses also clearly related to TTV but with a smaller genome, namely Torquetenominivirus (TTMV) and Torquetenomidivirus (TTMVD). Since 2009, all these viruses have been classified in the newly established family Anelloviridae (from anellus, Latin for "ring," to indicate the circular genome).

Despite the rapid accumulation of knowledge on TTV and related AVs, many fundamental aspects of their infection remain unresolved. Although AVs have been discovered to be extremely common, with abundant viral DNA detectable in the plasma of 80% or more of the general population worldwide, their significance for human health remains unknown. It has been proposed that AVs should be considered completely nonpathogenic, and the recent evidence that they represent the most abundant members of the human virome speaks in favor of this hypothesis. However, at this time, it seems wiser to consider AV an "orphan of disease", similar to what has previously been performed for many other viruses that, many years after their discovery, were found to produce significant pathologies.

Prof. Dr. Fabrizio Maggi
Dr. Pietro Giorgio Spezia
Guest Editors

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Keywords

  • TTV
  • TTMV
  • TTMDV
  • virome
  • viral species
  • immune system
  • orphan virus

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Related Special Issue

Published Papers (3 papers)

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Research

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11 pages, 3128 KB  
Article
Read-Level Error Characterization of Rolling-Circle Amplification-Based Nanopore Sequencing of the Circular DNA Virome
by Florencia Martino, Kakhangchung Panmei, Dylan Duchen, David L. Thomas, Abraham J. Kandathil and Steven J. Clipman
Viruses 2026, 18(7), 704; https://doi.org/10.3390/v18070704 - 26 Jun 2026
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Abstract
Oxford Nanopore technology enables cost-effective, portable, long-read analyses of pathogen genomes. Accurate detection and interpretation of small circular viral genomes, including Anelloviridae, remain challenging due to limited base-level error quantification in rolling-circle amplification (RCA)-derived datasets. Here, we characterized read-level sequencing error profiles [...] Read more.
Oxford Nanopore technology enables cost-effective, portable, long-read analyses of pathogen genomes. Accurate detection and interpretation of small circular viral genomes, including Anelloviridae, remain challenging due to limited base-level error quantification in rolling-circle amplification (RCA)-derived datasets. Here, we characterized read-level sequencing error profiles using M13mp18, a 7.2 kb circular phage genome, subjected to 1X and 3X shearing during library preparation. M13mp18 DNA was serially diluted into pooled anellovirus-positive plasma DNA extracts. Using custom error-analysis pipelines, we quantified mismatch, insertion, and deletion rates and evaluated consensus reconstruction accuracy across simulated sequencing depths. Since metagenomic viromes contain mixtures of related genomes and uneven coverage across taxa, depth-normalized subsampling was used to assess the precision of read-level error estimates under heterogeneous coverage. Across four benchmarked datasets, per-base error rates ranged from 0.018 to 0.022 errors per aligned base. Complete M13mp18 reference reconstruction was achieved at input levels ≥ 4.6 log10 copies, and consensus sequences reached 100% identity at depths ≥ 15X when sufficient reads were available. Below 4.6 log10 input copies, recovery was inconsistent. These findings provide a controlled empirical characterization of read-level error behavior in RCA-derived nanopore sequencing and support the interpretation of circular DNA virome data generated in complex metagenomic backgrounds. Full article
(This article belongs to the Special Issue Advancing Research of Anelloviruses, Second Edition)
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15 pages, 2971 KB  
Article
Prior Infection with Torque Teno Virus Mitigates Influenza Pathology in Mice
by Md-Tariqul Islam, Brett Webb and Sheela Ramamoorthy
Viruses 2026, 18(3), 357; https://doi.org/10.3390/v18030357 - 15 Mar 2026
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Abstract
Respiratory infections caused by influenza viruses are frequently associated with coinfection by other infectious agents. Torque teno viruses (TTVs) are small DNA viruses that can function as opportunistic pathogens and are epidemiologically linked to influenza viruses as well as a broad spectrum of [...] Read more.
Respiratory infections caused by influenza viruses are frequently associated with coinfection by other infectious agents. Torque teno viruses (TTVs) are small DNA viruses that can function as opportunistic pathogens and are epidemiologically linked to influenza viruses as well as a broad spectrum of infectious and immune-mediated diseases. Among TTVs, swine torque teno viruses (TTSuVs) are unique in that they have been shown to act as primary pathogens. With the long-term objective of developing experimental tools to better understand inter-viral interactions, this study aimed to optimize a murine model of TTV and influenza virus coinfection. Experimental mice were inoculated with TTSuV1 on day 1 post infection (DPI 1), while phosphate-buffered saline (PBS)-treated mice served as negative controls. A subset of TTSuV1-infected mice was subsequently coinfected with the influenza A virus H1N1 (IAV) at either 12 or 27 days following TTSuV1 infection. An additional group of mice was maintained as an IAV only control. Mice infected with IAV were euthanized 72–84 h post-IAV infection, corresponding to DPI 15 and 30, respectively. Unexpectedly, gross and histopathological examination of lung tissues revealed that prior TTSuV1 infection significantly attenuated IAV-induced pathology in coinfected mice. Coinfected animals also exhibited a tendency toward reduced IAV replication in the lungs as measured by qPCR, TCID50 and HAs compared to mice infected with IAV alone, accompanied by lower levels of virus-specific antibodies to IAV at DPI 30 and TTSuV1 at DPI 15 respectively. At DPI 30, TTSuV1 genomic DNA levels in lung tissue and whole blood were higher in coinfected mice, suggestive of prolonged viremia in the coinfected group. Collectively, these findings establish baseline parameters for a murine TTV and influenza coinfection model and provide a foundation for future studies aimed at elucidating the molecular and immunological mechanisms underlying viral coinfections. Full article
(This article belongs to the Special Issue Advancing Research of Anelloviruses, Second Edition)
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Review

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28 pages, 2033 KB  
Review
Anelloviruses: From General Biology to Their Role as Biomarkers of Immune Competence in HIV Infection
by Alina R. Nokhova, Kirill A. Elfimov, Alexander M. Shestopalov, Natalya M. Gashnikova and Olga G. Kurskaya
Viruses 2026, 18(2), 235; https://doi.org/10.3390/v18020235 - 13 Feb 2026
Cited by 1 | Viewed by 1585
Abstract
Viruses of the family Anelloviridae represent a predominant component of the human virome across various anatomical sites, yet their clinical significance remains poorly understood. This review summarizes current data on the dynamics and functional interactions of anelloviruses with the immune system in the [...] Read more.
Viruses of the family Anelloviridae represent a predominant component of the human virome across various anatomical sites, yet their clinical significance remains poorly understood. This review summarizes current data on the dynamics and functional interactions of anelloviruses with the immune system in the context of human immune deficiency virus (HIV) infection. Existing studies indicate that an individual’s complement of anelloviruses (their “anellome”) serves as a highly sensitive indicator of immunocompetence. In the absence of antiretroviral therapy (ART), the viral load and taxonomic diversity of anelloviruses (genera Alphatorquevirus, Betatorquevirus, and Gammatorquevirus) demonstrate a rapid increase, correlating with HIV viral load, a decline in CD4+ T-lymphocyte count, and the CD4/CD8 ratio, reflecting weakened immune surveillance. Upon initiation of antiretroviral therapy (ART), a decrease in anellovirus viral load is observed; however, it likely does not revert to the pre-HIV infection baseline. At the same time, a high baseline level of Torque teno virus (TTV) is associated with incomplete immune recovery and the risk of ART non-response. Anelloviruses exhibit a dual role as both activators of the immune system (via APOBEC3, antibody production, and pro-inflammatory cytokines resulting from Toll-like receptor (TLR) activation) and disruptors of certain signaling pathways (through micro-RNAs and proteins encoded by ORF2). Thus, monitoring the anellome represents a promising non-invasive approach for assessing immune status, risk stratification, and personalizing therapy in patients with HIV infection. Future research should focus on the practical application of anellovirus viral load and diversity as markers of immune status and on clarifying the consequences of the aggregate interaction between HIV modulator proteins and anelloviruses during co-infection. Full article
(This article belongs to the Special Issue Advancing Research of Anelloviruses, Second Edition)
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