Torque Teno Midi Virus Research Articles

Plasma metagenomics reveals regional variations of emerging and re-emerging pathogens in Chinese blood donors with an emphasis on human parvovirus B19

At present, many infectious pathogens, especially emerging/re-emerging pathogens, exist in the blood of voluntary blood donors and may be transmitted through blood transfusions. However, most of Chinese blood centers only routinely screen for HBV, HCV, HIV, and syphilis. We employed metagenomic next-generation sequencing (mNGS) to investigate the microbiome in healthy voluntary blood donors to help assess blood safety in China by identifying infectious pathogens presented in donations that could lead to transfusion-acquired infections. We collected 10,720 plasma samples from voluntary blood donors from seven blood centers in different cities during 2012–2018 in China. A total of 562 GB of clean data was obtained. By analyzing the sequencing data, it was found that the most commonly identified bacteria found in the healthy blood were Serratia spp. (5.0176%), Pseudomonas spp. (0.6637%), and Burkholderia spp. (0.5544%). The principal eukaryote were Leishmania spp (1.3723%), Toxoplasma gondii (0.6352%), and Candida dubliniensis (0.1848%). Among viruses, Human Parvovirus B19 (B19V) accounts for the highest proportion (0.1490%), followed by Torque teno midi virus (0.0032%) and Torque teno virus (0.0015%). Since that B19V is a non-negligible threat to blood safety, we evaluated the positive samples for B19V tested by mNGS using quantitative polymerase chain reaction, Sanger sequencing, and phylogenetic analysis to achieve a better understanding of B19V in Chinese blood donors. Subsequently, 9 (0.07%) donations were positive for B19V DNA. The quantitative DNA levels ranged from 5.58 × 102 to 7.24 × 104 IU/ml. The phylogenic analyses showed that prevalent genotypes belonged to the B19-1A subtype, which disclosed previously unknown regional variability in the B19V positivity rate. The investigation revealed that many microbes dwell in the blood of healthy donors, including some pathogens that may be dormant in the blood and only cause disease under specific conditions. Thus, investigating the range and nature of potential pathogens in the qualified donations provided a framework for targeted interventions to help prevent emerging and re-emerging infectious diseases.

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.

Metagenomic analysis reveals differences in the co-occurrence and abundance of viral species in SARS-CoV-2 patients with different severity of disease

BackgroundSARS-CoV-2 infections have a wide spectrum of clinical manifestations whose causes are not completely understood. Some human conditions predispose to severe outcome, like old age or the presence of comorbidities, but many other facets, including coinfections with other viruses, remain poorly characterized.MethodsIn this study, the eukaryotic fraction of the respiratory virome of 120 COVID-19 patients was characterized through whole metagenomic sequencing.ResultsGenetic material from respiratory viruses was detected in 25% of all samples, whereas human viruses other than SARS-CoV-2 were found in 80% of them. Samples from hospitalized and deceased patients presented a higher prevalence of different viruses when compared to ambulatory individuals. Small circular DNA viruses from the Anneloviridae (Torque teno midi virus 8, TTV-like mini virus 19 and 26) and Cycloviridae families (Human associated cyclovirus 10), Human betaherpesvirus 6, were found to be significantly more abundant in samples from deceased and hospitalized patients compared to samples from ambulatory individuals. Similarly, Rotavirus A, Measles morbillivirus and Alphapapilomavirus 10 were significantly more prevalent in deceased patients compared to hospitalized and ambulatory individuals.ConclusionsResults show the suitability of using metagenomics to characterize a broader peripheric virological landscape of the eukaryotic virome in SARS-CoV-2 infected patients with distinct disease outcomes. Identified prevalent viruses in hospitalized and deceased patients may prove important for the targeted exploration of coinfections that may impact prognosis.

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.

Virome definition in cerebrospinal fluid of patients with neurological complications after hematopoietic stem cell transplantation

BackgroundNeurological complications (NC) in allogeneic hematopoietic stem cell transplant (HSCT) recipients lead to long-term sequelae and result in significant morbidity and mortality. Since risk factors for NC include viral infection or reactivation, virome inspection after HSCT might be helpful to the clinical management of patients after HSCT. Objectives and study designIn this study we investigated whether any viruses are found in association with NC after HSCT. For this purpose, unbiased next generation sequencing (NGS) was used to characterize nucleic acid (NA) content in cerebrospinal fluid (CSF) taken at time of NC in 35 HSCT patients. Virome definition in CSF from non-transplanted subjects (controls) was also tested to define the commensal flora. Results and conclusionsA higher number of reads/contigs mapped to viruses in patients compared to the controls (7,626 vs 235). Besides bacteriophages, Torque teno virus (TTV) was also identified in both controls and patients. Interestingly, a significantly higher number of TTV-like sequences was detected in the patient samples (7,236 vs 9), showing similarities to distinct genotypes; 3/2,575, 2/1,692 and 2/2,969 contigs/reads mapped to TTV11, TTV13 and Torque teno midi virus, respectively.In conclusion, unbiased NGS demonstrated to be a suitable approach to characterize the virome in samples containing limiting amounts of NA. The higher TTV levels and genetic diversity found in CSF of subjects with NC after HSCT might suggest a possible association between TTV reactivation and the disorder. However, further studies are needed to evaluate the possible role of TTV on NC in HSCT patients.

Metagenomic analysis of viral diversity in respiratory samples from patients with respiratory tract infections in Kuwait.

A metagenomic approach based on target independent next‐generation sequencing has become a known method for the detection of both known and novel viruses in clinical samples. This study aimed to use the metagenomic sequencing approach to characterize the viral diversity in respiratory samples from patients with respiratory tract infections. We have investigated 86 respiratory samples received from various hospitals in Kuwait between 2015 and 2016 for the diagnosis of respiratory tract infections. A metagenomic approach using the next‐generation sequencer to characterize viruses was used. According to the metagenomic analysis, an average of 145, 019 reads were identified, and 2% of these reads were of viral origin. Also, metagenomic analysis of the viral sequences revealed many known respiratory viruses, which were detected in 30.2% of the clinical samples. Also, sequences of non‐respiratory viruses were detected in 14% of the clinical samples, while sequences of non‐human viruses were detected in 55.8% of the clinical samples. The average genome coverage of the viruses was 12% with the highest genome coverage of 99.2% for respiratory syncytial virus, and the lowest was 1% for torque teno midi virus 2. Our results showed 47.7% agreement between multiplex Real‐Time PCR and metagenomics sequencing in the detection of respiratory viruses in the clinical samples. Though there are some difficulties in using this method to clinical samples such as specimen quality, these observations are indicative of the promising utility of the metagenomic sequencing approach for the identification of respiratory viruses in patients with respiratory tract infections.

THE FIRST TWO CASES OF CHRONIC HEPATITIS ASSOCIATED WITH TORQUE TENO MIDI VIRUS (TTMDV), GENUS GAMMATORQUEVIRUS

The prevalence of Anelloviridae virus is high among population in many countries. The hepatotropic and hepatopathogenic features were confirmed in some genotypes of this family. Two chronic hepatitis B clinical cases associated with Torque teno midi virus (TTMDV, genus Gammatorquevirus) in the absence of other Anelloviruses and hepatotropic viruses (HBV, HCV, GBV -C, CMV) were described by using of molecular-biological, histopathological, immu nohistochemical and electron microscopy methods.

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.

Rapid Detection of Human Torque Teno Viruses Using High-Resolution Melting Analysis

Torque teno viruses (TTVs) are recently discovered DNA viruses, with heterogeneous genomes, highly prevalent in populations worldwide. The species that infect humans are Torque teno virus (TTV), Torque teno midi virus (TTMDV) and Torque teno mini virus (TTMV). High-resolution melting analysis (HRMA) is a sensitive and effective method for genotyping and mutation scanning. Up to now, HRMA has not been utilized for detection of TTVs. The aim of this study was to asses if HRMA is suitable for detecting TTVs variants. DNA was extracted from the blood and saliva of 13 healthy subjects for method optimization. Additionally, saliva samples from 100 healthy individuals were collected for estimating the TTVs' prevalence. Viral DNA was amplified by heminested polymerase chain reaction (PCR). Second round amplicons were used for the HRMA. The samples were analyzed using two fluorescent dyes, SYBR (®) Green I and EvaGreen®. The prevalence values for TTV, TTMDV and TTMV were 71.0, 31.0 and 54.0%, respectively. The three major melting curve patterns corresponding to TTV, TTMDV and TTMV on HRMA can be easily distinguished regardless of kit used. Our results showed that HRMA is a rapid and efficient method of detecting human TTVs.

Detection of torque teno midi virus/small anellovirus (TTMDV/SAV) in chronic cervicitis and cervical tumors in Isfahan, Iran

Torque teno midi virus and small anellovirus (TTMDV/SAV) are members of the genus Gammatorquevirus within the family Anelloviridae. Cervical cancer is the second most prevalent cancer after breast cancer. The aim of this study was to determine the frequency of infection by these viruses in cervicitis and cervical tumors of women from Isfahan, Iran. Formalin-fixed, paraffin-embedded tissue samples from cervical cancers (n=42) and cervicitis cases (n=79) were subjected to nested PCR to identify TTMDV/SAV viral sequences. Of the 42 tumor cases, 22, 18 and 2 were diagnosed as adenocarcinoma, cervical intraepithelial neoplasia and squamous cell carcinoma, respectively. In total, 23 (55%) of the tumor samples were positive for TTMDV/SAV. Of the 79 cervicitis cases, 38 (48%) were also positive for TTMDV/SAV. This is the first report of TTMDV/SAV in cervicitis and cervical tumors of women.

Sequence analysis of a Torque teno canis virus isolated in China

In the present study, a total of 158 fecal samples were collected from diarrheal dogs younger than 1 year old in pet clinic in China. 20 specimens (20/158, 13%) were positive for Torque teno canis virus DNA using detection PCR. One representative positive isolate designated LDL was randomly selected, cloned and sequenced. The complete genome of the LDL Chinese strain was 2799 nucleotides in length and contains three open reading frames (ORFs), which encode 576 (ORF1), 101 (ORF2), and 243 (ORF3) aa. Compared with the human and other animal TTV genomes, the genome of the LDL strain is clearly smaller and shares 95% identity with Japanese cf-TTV10 strain (AB076002). Phylogenetic analysis showed that the present Chinese Torque teno canis virus LDL strain was also closely clustered with the previous Japanese cf-TTV10 strain, and formed a different branch together with Torque teno sus viruses 1 and 2 compared with other Torque teno viruses, Torque teno mini virus, and Torque teno midi virus. Our study demonstrated that Torque teno canis virus is present in China.

Detection and follow-up of torque teno midi virus (“small anelloviruses”) in nasopharyngeal aspirates and three other human body fluids in children

Torque teno midi virus/small anellovirus (TTMDV/SAV) is a member of the family Anelloviridae. It has a single-stranded, circular, negative-sense DNA genome. Its pathogenic role in human disease remains to be confirmed. In this study, viral shedding, molecular epidemiology and genetic diversity of TTMDV/SAV were studied in human body fluids. Nasopharyngeal aspirates collected from children with acute respiratory disease were tested by PCR/nested PCR for TTMDV/SAV in two seasons (2005/2006, 2006/2007). Two years later, additional urine, stool, and serum samples and nasopharyngeal aspirates were collected from eight symptomless children for follow-up investigation. Forty-three (46.7%) of the 92 nasopharyngeal aspirates collected contained TTMDV/SAV. High genetic diversity was observed; however, identical sequences were also detected in two patients. The mean age of the infected children was 3 years (1 months-8 years), and 58% of them were female. Co-infection with RSV was detected in 23% of the samples. In a follow-up study, nasopharyngeal aspirates and serum of six (75%), stool samples of four (50%) and urine samples of two (25%) of the eight children were anellovirus-positive. None of the anellovirus sequences were identical in the two collection periods, but identical sequences were detected in different body fluids collected at the same time from the same child. TTMDV/SAVs shedding was detected in four human body fluids. As a consequence, it is possible that generalized infection and fecal/uro-oral transmission of TTMDV/SAV occur. TTMDV/SAVs are frequently present in nasopharyngeal aspirates, although the variants may only be transient agents. Further research is needed to investigate the pathogenesis and pathogenic role of TTMDV/SAV.

Transfusion transmission of highly prevalent commensal human viruses

Anellovirus species Torque teno virus (TTV), Torque teno mini virus (TTMV), and Torque teno midi virus (TTMDV) and flavivirus GBV-C are highly prevalent and genetically diverse chronic human viral infections that have not yet been associated with disease. To determine if these commensal viruses are transmitted by blood transfusions, we genetically analyzed viral species in cryopreserved samples from blood donors and corresponding pre- and posttransfusion samples from recipients enrolled in the Transfusion-Transmitted Viruses Study cohort. All 24 individuals in 12 donor-recipient pairs were infected with TTV, while 16 were infected with TTMV, 15 with TTMDV, and four with GBV-C. None of the 12 informative cases of TTV transfusion or eight cases of TTMV transfusion, where the donor and recipient viruses could be genetically differentiated, resulted in detectable transmissions in which the donor viruses were detected in the recipient by direct sequencing of the polymerase chain reaction products. Of the five informative cases of TTMDV transfusion, including two cases of transfusion into TTMDV-negative recipients, one case of superinfection was seen with both the recipient and the donor viral variants detected in the transfusion recipient for at least 11 days posttransfusion. Three donor-recipient pairs were informative for GBV-C transmission with only one transfusion into a GBV-C-negative recipient resulting in a transiently detected infection. Transmission of the common commensal anelloviruses and GBV-C during transfusion was detected in 2 of 12 already infected or uninfected recipients. Underestimation of the true rate of viral transmission may be due to limitations in detecting donor viral variants present as minority variants in the already infected transfusion recipients.