Torque Teno Mini Virus Research Articles

Over-Representation of Torque Teno Mini Virus 9 in a Subgroup of Patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A Pilot Study.

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a chronic disorder classified by the WHO as postviral fatigue syndrome (ICD-11 8E49 code). Diagnosing ME/CFS, often overlapping with fibromyalgia (FM), is challenging due to nonspecific symptoms and lack of biomarkers. The etiology of ME/CFS and FM is poorly understood, but evidence suggests viral infections play a critical role. This study employs microarray technology to quantitate viral RNA levels in immune cells from ME/CFS, FM, or co-diagnosed cases, and healthy controls. The results show significant overexpression of the Torque Teno Mini Virus 9 (TTMV9) in a subgroup of ME/CFS patients which correlate with abnormal HERV and immunological profiles. Increased levels of TTMV9 transcripts accurately discriminate this subgroup of ME/CFS patients from the other study groups, showcasing its potential as biomarker for patient stratification and the need for further research into its role in the disease. Validation of the findings seems granted in extended cohorts by continuation studies.

Acute Promyelocytic Leukemia With Torque Teno Mini Virus::RARA Fusion: An Approach to Screening and Diagnosis

Acute promyelocytic leukemia (APL) with variant RARA translocation is linked to over 15 partner genes. Recent publications encompassing 6 cases have expanded the spectrum of RARA partners to torque teno mini virus (TTMV). This entity is likely underrecognized due to the lack of clinician and pathologist familiarity, inability to detect the fusion using routine testing modalities, and informatic challenges in its recognition within next-generation sequencing (NGS) data. We describe a clinicopathologic approach and provide the necessary tools to screen and diagnose APL with TTMV::RARA using existing clinical DNA- or RNA-based NGS assays, which led to the identification of 4 cases, all without other known cytogenetic/molecular drivers. One was identified prospectively and 3 retrospectively, including 2 from custom automated screening of multiple data sets (50,257 cases of hematopoietic malignancy, including 4809 acute myeloid leukemia/myeloid sarcoma/APL cases). Two cases presented as myeloid sarcoma, including 1 with multiple relapses after acute myeloid leukemia-type chemotherapy and hematopoietic stem cell transplant. Two cases presented as leukemia, had a poor response to induction chemotherapy, but achieved remission upon reinduction (including all-trans retinoic acid in 1 case) and subsequent hematopoietic stem cell transplant. Neoplastic cells demonstrated features of APL including frequent azurophilic granules and dim/absent CD34 and HLA-DR expression. RARA rearrangement was not detected by karyotype or fluorescent in situ hybridization. Custom analysis of NGS fusion panel data identified TTMV::RARA rearrangements and, in the prospectively identified case, facilitated monitoring in sequential bone marrow samples. APL with TTMV::RARA is a rare leukemia with a high rate of treatment failure in described cases. The diagnosis should be considered in leukemias with features of APL that lack detectable RARA fusions and other drivers, and may be confirmed by appropriate NGS tests with custom informatics. Incorporation of all-trans retinoic acid may have a role in treatment but requires accurate recognition of the fusion for appropriate classification as APL.

Potential of Viruses as Environmental Etiological Factors for Non-Syndromic Orofacial Clefts.

In this study, we analyzed the potential of viral infections in the species Homo sapiens as environmental causes of orofacial clefts (OFCs). A scoring system was adapted for qualitatively assessing the potential of viruses to cause cleft lip and/or palate (CL/P). This assessment considered factors such as information from the literature, nucleotide and amino acid similarities, and the presence of Endogenous Viral Elements (EVEs). The analysis involved various algorithm packages within Basic Local Alignment Search Tool 2.13.0 software and databases from the National Center for Biotechnology Information and the International Committee on Taxonomy of Viruses. Twenty significant viral species using different biosynthesis strategies were identified: Human coronavirus NL63, Rio Negro virus, Alphatorquevirus homin9, Brisavirus, Cosavirus B, Torque teno mini virus 4, Bocaparvovirus primate2, Human coronavirus HKU1, Monkeypox virus, Mammarenavirus machupoense, Volepox virus, Souris mammarenavirus, Gammapapillomavirus 7, Betainfluenzavirus influenzae, Lymphocytic choriomeningitis mammarenavirus, Ledantevirus kern, Gammainfluenzavirus influenzae, Betapolyomavirus hominis, Vesiculovirus perinet, and Cytomegalovirus humanbeta5. The evident viral etiological potential in relation to CL/P varies depending on the Baltimore class to which the viral species belongs. Given the multifactorial nature of CL/P, this relationship appears to be dynamic.

Maternal plasma and salivary anelloviruses in pregnancy and preterm birth.

Human anelloviruses, including torque teno virus (TTV) and torque teno mini virus (TTMV), are ubiquitous in the general population and have no known pathogenicity. We investigated the prevalence and viral load of TTV and TTMV in plasma and saliva over pregnancy, and assessed their association with spontaneous or medically indicated preterm birth. This is a secondary analysis of the Measurement of Maternal Stress (MOMS) study, which recruited 744 individuals with singleton pregnancies from 4 US sites (Chicago, Pittsburgh, San Antonio, and rural Pennsylvania). Baseline outpatient visits took place in the second trimester (between 12'0 and 20'6/7 weeks' gestation), and follow-up visits in the third trimester (between 32'0 and 35'6/7 weeks' gestation). In a case-control study design, participants who delivered preterm (<37 weeks) resulting from spontaneous labor and/or preterm premature rupture of membranes ("sPTB") were compared with participants experiencing medically indicated preterm birth ("iPTB"), or delivery at term ("controls"). Plasma and saliva samples obtained during the second and third trimesters were tested for the presence and quantity of TTV and TTMV using real-time PCR. Demographic data were obtained via self-report, and clinical data via medical record review by trained research personnel. TTV was detected in plasma from 81% (second trimester) and 77% (third trimester) of participants, and in saliva from 64 and 60%. Corresponding detection rates for TTMV were 59 and 41% in plasma, and 35 and 24% in saliva. TTV and TTMV concentrations were similar between matched plasma and saliva samples. TTV prevalence and concentrations were not significantly different between groups (sPTB, iPTB, and controls). However, plasma TTMV in the third trimester was associated with sPTB and earlier gestational age at delivery. The iPTB group was not different from either the sPTB or the control group. In saliva, concentrations of TTV and TTMV were similar among the three groups. Both TTV and TTMV were more prevalent with increasing parity and were more common in Black and Hispanic participants compared to non-Hispanic White participants. Anellovirus presence (specifically, TTMV) in the third trimester may be associated with preterm birth. Whether this association is causative remains to be determined.

Human Anelloviruses: Influence of Demographic Factors, Recombination, and Worldwide Diversity.

Anelloviruses represent the major and most diverse component of the healthy human virome, referred to as the anellome. In this study, we determined the anellome of 50 blood donors, forming two sex- and age-matched groups. Anelloviruses were detected in 86% of the donors. The number of detected anelloviruses increased with age and was approximately twice as high in men as in women. A total of 349 complete or nearly complete genomes were classified as belonging to torque teno virus (TTV), torque teno mini virus (TTMV), and torque teno midi virus (TTMDV) anellovirus genera (197, 88, and 64 sequences, respectively). Most donors had intergenus (69.8%) or intragenus (72.1%) coinfections. Despite the limited number of sequences, intradonor recombination analysis showed 6 intragenus recombination events in ORF1. As thousands of anellovirus sequences have been described recently, we finally analyzed the global diversity of human anelloviruses. Species richness and diversity were close to saturation in each anellovirus genus. Recombination was found to be the main factor promoting diversity, although its effect was significantly lower in TTV than in TTMV and TTMDV. Overall, our results suggest that differences in diversity between genera may be caused by variations in the relative contribution of recombination. IMPORTANCE Anelloviruses are the most common human infectious viruses and are considered essentially harmless. Compared to other human viruses, they are characterized by enormous diversity, and recombination is suggested to play an important role in their diversification and evolution. Here, by analyzing the composition of the plasma anellome of 50 blood donors, we find that recombination is also a determinant of viral evolution at the intradonor level. On a larger scale, analysis of anellovirus sequences currently available in databases shows that their diversity is close to saturation and differs among the three human anellovirus genera and that recombination is the main factor explaining this intergenus variability. Global characterization of anellovirus diversity could provide clues about possible associations between certain virus variants and pathologies, as well as facilitate the implementation of unbiased PCR-based detection protocols, which may be relevant for using anelloviruses as endogenous markers of immune status.

Torque teno viruses implications on chronic myeloid leukemia

Chronic myeloid leukemia (CML) is a hematological malignancy characterized by the presence of BCR-ABL+ and Ph+. According to recent studies, CML occurence and evolution are influenced by a series of risk factors, including viruses. Multiple studies suggested that Torque teno viruses (TTVs) could modulate the treatment response and the evolution of hematological diseases. This study focuses on identifying the prevalence and clinical significance of TTVs in CML patients. The main aim was to determine if TTVs presence can be correlated with the onset of disease. We performed a retrospective study (2018-2022) that included 72 blood samples from patients diagnosed with CML. All the 3 anelloviruses were detected using hemi-nested PCR. The overall frequency of TTVs in blood samples was 93%. In our study group, most patients were carriers for the Torque teno virus (TTV), Torque teno midi virus (TTMDV) and Torque teno mini virus (TTMV) in 88%, 57% and 63% of samples. The largest group of carriers was represented by patients with all 3 anelloviruses (51,38%), followed by TTV (22,22%). In our study group represented by CML patients at diagnosis, the prevalence of TTVs is correlated with the molecular load of BCR-ABL. Further research and follow-up of patients with TTV are needed in the future, as well as the identification of new factors that can help to personalize treatment.

Regional mutations in CHIKV-ECSA genomes and detection of other viruses in the serum of acute febrile patients by a metagenomic approach in Mato Grosso, Central-Western Brazil, 2018

Mato Grosso (MT) State is part of central western Brazil and has a tropical permissive environment that favors arbovirus outbreaks. A metagenomic approach was used to identify viral genomes in seven pools of serum from patients (n=65) with acute febrile disease. Seven chikungunya virus (CHIKV) genomes were determined, showing four amino acid changes found only in CHIKV genomes obtained in MT since 2018: nsP2:T31I, nsP3: A388V, E3:T201I and E3:H57R, in addition to other mutations in E1, nsP2 and nsP4. Six parvovirus B19 (B19V) genotype I genomes (4771–5131 nt) showed four aa alterations (NS1:N473D, R579Q; VP1:I716T; and 11 kDa:V44A) compared to most similar B19V from the USA. Coinfection between CHIKV and B19V was evidenced in 22/65 (33.8%) patients by RT‒PCR and PCR, respectively. Other viruses found in these pools include human pegivirus C, torque teno virus 3, an unclassified TTV and torque teno mini virus. Metagenomics represents a useful approach to detect viruses in the serum of acute febrile patients suspected of arbovirus disease.

Diversity and Long-Term Dynamics of Human Blood Anelloviruses.

ABSTRACTAnelloviruses (AVs) are commensal members of the human blood virome. Even though it was estimated that over 90% of the human population carries AVs, the dynamics of the AV virome (“anellome”) are unknown. We investigated the dynamics of blood anellomes in two healthy people followed up for more than 30 years. Both subjects were positive for AVs in the majority of samples. Alphatorquevirus (torque teno virus [TTV]) was the most common genus in both subjects, followed by Betatorquevirus (torque teno minivirus [TTMV]) and Gammatorquevirus (torque teno midivirus [TTMDV]). Almost five times more lineages were found in subject 1 than in subject 2, and the anellomes differed phylogenetically. Both anellomes remained compositionally stable, and 9 out of 64 AV lineages were detected in over half of the time points. We confirmed the long-term and short-term persistence of 13 lineages by specific quantitative PCR (qPCR). AV lineages were detected in blood for over 30 years. Noticeable differences in anellome richness were found between the tested subjects, but both anellomes remained compositionally stable over time. These findings demonstrate that the human blood anellome is personal and that AV infection is chronic and potentially commensal.IMPORTANCE Knowledge of the persistence of AVs in humans is crucial to our understanding of the nature of AV infection (chronic or acute) and the role of AV in the host. We therefore investigated the dynamics of anellovirus infection in two healthy people followed up for 30 years. Our findings suggest that the human blood anellovirus virome (anellome) remains stable and personal for decades.

Metagenomic Analysis Reveals High Abundance of Torque Teno Mini Virus in the Respiratory Tract of Children with Acute Respiratory Illness.

Human Anelloviridae is a highly prevalent viral family, including three main genera—Alphatorquevirus (Torque teno virus, TTV), Betatorquevirus (Torque teno mini virus, TTMV), and Gammatorquevirus (Torque teno midi virus, TTMDV). To date, the characterization of Anelloviridae in the respiratory tract of children with acute respiratory infection (ARI) has been poorly reported and mainly focused on TTV. We performed a metagenomic analysis of eight respiratory samples collected from children with an ARI of unknown etiology (eight samples tested negative with a multiplex PCR assay, out of the 39 samples initially selected based on negative routine diagnostic testing). A total of 19 pediatric respiratory samples that tested positive for respiratory syncytial virus (RSV, n = 13) or influenza virus (n = 6) were also sequenced. Anelloviridae reads were detected in 16/27 samples, including 6/8 negative samples, 7/13 RSV samples and 3/6 influenza samples. For samples with a detection of at least one Anelloviridae genus, TTMV represented 87.1 (66.1–99.2)% of Anelloviridae reads, while TTV and TTMDV represented 0.8 (0.0–9.6)% and 0.7 (0.0–7.1)%, respectively (p < 0.001). Our findings highlight a high prevalence of TTMV in respiratory samples of children with an ARI of unknown etiology, as well as in samples with an RSV or influenza infection. Larger studies are needed to explore the role of TTMV in childhood respiratory diseases.

Human Anelloviruses: Prevalence and Clinical Significance During Pregnancy

Although the bacterial microbiota of various compartments (e.g. vagina, amniotic fluid, and placenta) have been studied in pregnancy, there has been far less emphasis on normal and pathological viral communities. Cumulative evidence shows the presence of a number of apathogenic viruses in various tissues of healthy people, including pregnant individuals. What role, if any, these viruses play in human physiology is unknown. Anelloviruses (family Anelloviridae) are circular, single-stranded DNA viruses commonly detected with high prevalence in vertebrate hosts, including primates. Humans are nearly always colonized with at least 1 of 3 anellovirus subtypes, namely Alphatorquevirus (torque teno virus, TTV), Betatorquevirus (torque teno midi virus, TTMDV), and Gammatorquevirus (torque teno mini virus, TTMV). In healthy pregnant people, the prototype anellovirus, TTV, has been found in maternal and (variably) fetal blood, amniotic fluid, cervical and vaginal secretions, breast milk, and saliva. Nonetheless, the relevance of human anelloviruses in pregnancy and labor is unclear. There is evidence suggesting a link between anellovirus colonization and preterm birth. In this review, we discuss what is known about this family of commensal viruses in health and disease, and specifically the roles they might play during pregnancy and in the timing of delivery.

Diversity and dynamic changes of anelloviruses in plasma following allogeneic hematopoietic stem cell transplantation.

Monitoring of alphatorquevirus (torque teno virus [TTV]) DNA in plasma may prove to be useful to assess the net state of immune competence following allogeneic hematopoietic stem cell transplantation (allo-HSCT). There are scarce data published on the prevalence of beta (torque teno mini virus [TTMV]) and gammatorqueviruses (torque teno midi virus [TTMDV]) and, in particular, on the dynamics of anelloviruses in allo-HSCT patients. Twenty-five allo-HSCT recipients with available plasma specimens obtained before conditioning and after engraftment were included. Degenerated primers targeting a highly conserved genomic sequence across all anelloviruses were designed for genomic amplification and high-throughput sequencing. Co-detection of TTV, TTMV, and TTMDV both in pre-transplant and post-engraftment plasma specimens was documented in more than two-thirds of patients. The use of quantitative real-time polymerase chain reaction (PCR) assays targeting TTMV and TTMDV in addition to TTV may add value to TTV-specific PCR assays in the inference of the net state of immunosuppresion or immune competence in this clinical setting.

Occurrence and quantification of Anelloviruses and Herpesviruses in gingival tissue in Chinese Shanghai sub-population

BackgroundHerpesviruses and bacteria and their interplay have long been believed to play important roles in the pathogenesis of periodontitis, but other microbial entities in the oral environment might also be involved. Anelloviruses are commonly detected in human, including in oral samples. The aim of the present study was to explore the occurrence and co-occurrence of human cytomegalovirus (HCMV), Epstein–Barr virus (EBV), and human anelloviruses (HTTVs) in gingival tissue samples collected from participants recruited in Shanghai, China.MethodsGingival tissues were collected from 159 participants (57 with aggressive periodontitis (AP), 59 with chronic periodontitis (CP) and 43 with healthy periodontal status). The presence of HCMV, EBV, torque teno virus (TTV), torque teno mini virus (TTMV) and torque teno midi virus (TTMDV) DNA was detected by nested-PCR. The virus loads were quantified by real-time PCR.ResultsThe detection rates of EBV, TTV, TTMV and TTMDV were significantly higher in the AP and CP groups compared to the healthy group (all P < 0.01). A statistically significant association was found between EBV, TTV and TTMV virus load and periodontitis (all P < 0.05). Participants infected with EBV showed significantly higher infection rates and higher virus loads of TTV and TTMV than the EBV-negative group (all P < 0.05). The coexistence rates of EBV and anelloviruses and the coexistence of three HTTVs were significantly higher in AP and CP groups (all P < 0.01).ConclusionsCollectively, results obtained in this study suggest that HTTVs and the coexistence of EBV and HTTVs in particular, may be associated with periodontitis. Possible mechanisms of the interaction between herpesviruses and anelloviruses in the context of periodontitis require further investigation.

Prevalence of torque viruses in HIV-infected and non-HIV-infected Nigerian subjects: analysis of near-full-length genome sequences.

Torque teno virus (TTV), torque teno mini virus (TTMV) and torque teno midi virus (TTMDV) are members of the family Anelloviridae that are known to infect humans. Although no pathogenic roles have been associated with anelloviruses, their high prevalence and perceived ubiquitousness have provoked scientific interest in understanding their molecular and biological characteristics. We used nested PCR to determine the prevalence of anelloviruses among 130 human immunodeficiency virus (HIV)-infected patients and 130 healthy blood donors, and analyzed three near-full-length genome sequences of TTV isolates from HIV-infected and non-HIV infected Nigerians. Statistical analysis showed that the rate of TTV infection was significantly higher in the HIV-infected group (65%) than in the blood donor group (26%) (p < 0.05, χ2 = 40.3). TTMV and TTMDV infections were very high in both groups, ranging between 88 and 95%. No significant association was found between TTV infection and age, sex, CD4+ cell count, HIV viral load or alanine aminotransferase (ALT) level. Near-full-length genome sequences of TTV isolates FL100, FL08 and BD67 determined by next-generation sequencing were 3.6 kb, 3.2 kb and 2.9 kb, respectively, in size. Their GenBank accession numbers are MK820644, MK820645, MK820646, respectively. These isolates shared 59% sequence identity across the whole genome and clustered in two different phylogenetic groups. Our study established for the first time the circulation of TTV, TTMV and TTMDV in the Nigerian population, with a disproportionately higher prevalence of TTV in HIV-infected patients. The near-complete TTV genome sequences from Nigeria are similar to the sequences KT163879 and KT163916 (3748 and 3190 respectively), obtained from the plasma of HIV-infected subjects from the United States, and EU305675 (2919), identified in human plasma samples from France.

СОЧЕТАННЫЕ ВИРУСНЫЕ ИНФЕКЦИИ У ПАЦИЕНТОВ С ХРОНИЧЕСКИМ ГЕПАТИТОМ В: РАСПРОСТРАНЕННОСТЬ И КЛИНИЧЕСКОЕ ЗНАЧЕНИЕ

Background. Hepatitis B virus (HBV) infection remains a global public health problem. Objective – to analyze the prevalence of viral coinfections with human immunodefciency virus (HIV), hepatitis C virus (HCV), hepatitis delta virus (HDV), TT-viruses and SENV in patients with chronic hepatitis B (CHB) and to assess their influence on liver disease severity. Material and methods. The observational cross-sectional study included 287 patients with chronic hepatitis B virus (HBV) – those with monoinfection and coinfected with HIV, HCV, HDV. Routine hematological and biochemical tests were performed, serum HBV DNA level as well as liver fbrosis stage were measured. Blood samples from 62 patients for Torque teno virus (TTV), Torque teno mini virus, Torque teno midi virus, SENV (D and H genotypes) DNAs were examined by polymerase chain reaction. Results. Among patients with CHB the prevalence of coinfection HBV + HIV is 6.6%, HBV + HCV – 6.3%, HBV + HDV – 3.8% and HBV + HDV + HCV – 1.7%. CHB patients coinfected with HIV, HCV, HDV had more pronounced biochemical differences and higher proportion of liver cirrhosis vs. HBV-monoinfected ones. The detection rate of TT viruses and their various combinations in patients with CHB is 91.9%, SENV – 66.1%. Conclusion. Coinfection with HIV, HCV, HDV in CHB patients is associated with more severe forms of chronic liver disease as compared to HBV-monoinfection. TT viruses and SENV are widespread and don’t affect the severity of liver disease in patients with CHB.

Metagenomic Investigation of Torque Teno Mini Virus-SH in Hematological Patients.

A new member of Anelloviridae, named torque teno mini virus (TTMV)-SH, was recently identified in the serum of three Hodgkin’s lymphoma patients suggesting that TTMV-SH may be associated with this type of hematological malignancy. We investigated by metagenomic analysis the presence of TTMV-SH-related viruses in plasma samples (n = 323) collected from patients with various hematological malignancies (multiple myeloma (MM, n = 256), non-Hodgkin’s lymphoma (NHL, n = 20), acute myeloid leukemia (n = 10)) and from healthy donors (n = 37). TTMV-SH-related strains were identified in 24 samples corresponding to four MM and one NHL patients. Phylogenic analysis revealed that the 24 isolates were close to the TTMV-SH strains previously identified, sharing 79.6–86.7% ORF1 nucleotide sequence identity. These results suggest that TTMV-SH-related viruses might be found in hematological diseases other than Hodgkin’s lymphoma. Due to the high genetic variability within Anelloviridae species, the association between a particular medical condition and a new genotype should be interpreted with caution.

Viral metagenomics revealed novel betatorquevirus species in pediatric inpatients with encephalitis/meningoencephalitis from Ghana

The cause of acute encephalitis/meningoencephalitis in pediatric patients remains often unexplained despite extensive investigations for large panel of pathogens. To explore a possible viral implication, we investigated the virome of cerebrospinal fluid specimens of 70 febrile pediatric inpatients with clinical compatible encephalitis/meningoencephalitis. Using viral metagenomics, we detected and genetically characterized three novel human Torque teno mini virus (TTMV) species (TTMV-G1-3). Phylogenetically, TTMV-G1-3 clustered in three novel monophyletic lineages within genus Betatorquevirus of the Anelloviridae family. TTMV-G1-3 were highly prevalent in diseased children, but absent in the healthy cohort which may indicate an association of TTMV species with febrile illness. With 2/3 detected malaria co-infection, it remains unclear if these novel anellovirus species are causative agents or increase disease severity by interaction with malaria parasites. The presence of the viruses 28 days after initiating antimalarial and/or antibiotic treatment suggests a still active viral infection likely as effect of parasitic and/or bacterial co-infection that may have initiated a modulated immune system environment for viral replication or a defective virus clearance. This study increases the current knowledge on the genetic diversity of TTMV and strengthens that human anelloviruses can be considered as biomarkers for strong perturbations of the immune system in certain pathological conditions.

A Novel Torque Teno Mini Virus in the Blood of the Patient With Lymphoma

Aim: To characterize a novel anellovirus and analyze the relationship of the novel anellovirus with other anelloviruses. Materials &amp; methods: Twenty-one serum samples of lymphoma patients were collected and viral metagenomics method was used to identify the novel anellovirus; CLUSTALW1.8 and MEGA6.0 was used to perform phylogenetic analysis; prevalence investigation was performed by nest PCR. Results: A novel anellovirus was discovered from two patients with lymphoma. The complete genome of torque teno mini virus (TTMV)-SHA is 2880 nt in length. Phylogenetic analysis based on ORF1 indicated that TTMV-SHA clusters with EF538882 sharing 62.5% sequence similarity, and the sequences divergence is 54%. Conclusion: TTMV (SHA) belonged to a novel anellovirus species, whether this novel anellovirus is associated with lymphoma needs further studies.

Two new species of betatorqueviruses identified in a human melanoma that metastasized to the brain.

The role of viral infections in the etiology of brain cancer remains uncertain. Prior studies mostly focused on transcriptome or viral DNA integrated in tumor cells. To investigate for the presence of viral particles, we performed metagenomics sequencing on viral capsid-protected nucleic acids from 12 primary and 8 metastatic human brain tumors. One brain tumor metastasized from a skin melanoma harbored two new human anellovirus species, Torque teno mini virus Emory1 (TTMV Emory1) and Emory2 (TTMV Emory2), while the remaining 19 samples did not reveal any exogenous viral sequences. Their genomes share 63-67% identity with other TTMVs, and phylogenetic clustering supports their classification within the Betatorquevirus genus. This is the first identification of betatorqueviruses in brain tumors. The viral DNA was in its expected non-integrated circular form, and it is unclear if the viruses contributed to tumor formation. Whether the viruses originated from blood, or the primary skin tumor could not be ascertained. Overall, our results demonstrate the usefulness of viral metagenomics to detect previously unknown exogenous virus in human brain tumors. They further suggest that active viral infections are rare events in brain tumors, but support a follow-up larger scale study to quantify their frequency in different brain tumor subtypes.

Detection of a new species of torque teno mini virus from the gingival epithelium of patients with periodontitis.

We describe a novel species of torque teno mini virus called TTMV-204, which was isolated from the gingival epithelium of patients with periodontitis and characterized using viral metagenomics. The sequence of the full genome is 2824 nt in length. Phylogenetic analysis and genetic analyses show classic Betatorquevirus species organization with less than 40% amino acid similarity in ORF1. The prevalence of TTMV-204 in the periodontitis patient population was 18.75% (15/80), which was higher than in periodontally healthy individuals (10.00%, 10/80). However, the difference of the TTMV-204 prevalence between two groups was not statistically significant (p=0.115). Further investigation is required to determine whether this new virus is associated with inflammation.

A novel species of torque teno mini virus (TTMV) in gingival tissue from chronic periodontitis patients.

A new species of torque teno mini virus, named TTMV-222, was detected in gingival tissue from periodontitis patients using a viral metagenomics method. The 2803-nucleotide genome of TTMV-222 is closely related to TTMV1-CBD279, with 62.6% overall nucleotide similarity. Genetic analyses of the new virus genome revealed a classic genomic organization but a weak identity with known sequences. The prevalence of TTMV-222 in the periodontitis group (n = 150) was significantly higher than that in the healthy group (n = 150) (p = 0.032), suggesting that the new virus may be associated with inflammation in chronic periodontitis patients. However, this finding requires further investigation.