Obesity is associated with a higher Torque Teno viral load compared to leanness.

Introduction: Obesity affects a rising proportion of the population and is an important risk factor for unfavorable outcomes in viral disease including severe acute respiratory syndrome coronavirus 2- associated diseases. Torque Teno virus (TTV) is a ubiquitous and apathogenic virus which reflects the immune function of its host. The aim of this study was to investigate the association between obesity and TTV load - an indirect marker of compromised viral immune response. Methods: TTV was quantified by TTV R-GENE® PCR in a total of 89 participants of which 30 were lean (BMI <25 kg/m2) and 59 were obese (BMI >30 kg/m2). For 38 subjects, follow-up was available after bariatric surgery. Results: TTV load was higher in individuals with obesity (median 2.39, IQR: 1.69-3.33 vs. 1.88, IQR 1.08-2.43 log10 copies/mL; p = 0.027). Multivariable linear modeling revealed an independent association between TTV load and obesity. TTV was positively correlated with waist-to-hip ratio and inversely with 25OH vitamin D levels. Interleukin 6 and fasting insulin resistance were confounders of the association between TTV and obesity, while age was an effect modifier. TTV load increased by 87% (95% CI 2-243%) in the year following bariatric surgery. Discussion: A higher TTV load in obese individuals may reflect compromised immune function and thus might serve for risk stratification of unfavorable outcomes during infectious disease, including coronavirus disease 2019, in this population. Our data warrant further analysis of TTV-based risk assessment in obese individuals in the context of infectious disease-associated outcomes.

Herpes DNAemia and TTV Viraemia in Intensive Care Unit Critically Ill Patients: A Single-Centre Prospective Longitudinal Study.

Introduction: We analysed blood DNAemia of TTV and four herpesviruses (CMV, EBV, HHV6, and HSV-1) in the REAnimation Low Immune Status Marker (REALISM) cohort of critically ill patients who had presented with either sepsis, burns, severe trauma, or major surgery. The aim was to identify common features related to virus and injury-associated pathologies and specific features linking one or several viruses to a particular pathological context. Methods: Overall and individual viral DNAemia were measured over a month using quantitative PCR assays from the 377 patients in the REALISM cohort. These patients were characterised by clinical outcomes [severity scores, mortality, Intensive Care Unit (ICU)-acquired infection (IAI)] and 48 parameters defining their host response after injury (cell populations, immune functional assays, and biomarkers). Association between viraemic event and clinical outcomes or immune markers was assessed using χ2-test or exact Fisher's test for qualitative variables and Wilcoxon test for continuous variables. Results: The cumulative incidence of viral DNAemia increased from below 4% at ICU admission to 35% for each herpesvirus during the first month. EBV, HSV1, HHV6, and CMV were detected in 18%, 12%, 10%, and 9% of patients, respectively. The incidence of high TTV viraemia (>10,000 copies/ml) increased from 11% to 15% during the same period. Herpesvirus viraemia was associated with severity at admission; CMV and HHV6 viraemia correlated with mortality during the first week and over the month. The presence of individual herpesvirus during the first month was significantly associated (p < 0.001) with the occurrence of IAI, whilst herpesvirus DNAemia coupled with high TTV viraemia during the very first week was associated with IAI. Herpesvirus viraemia was associated with a lasting exacerbated host immune response, with concurrent profound immune suppression and hyper inflammation, and delayed return to immune homeostasis. The percentage of patients presenting with herpesvirus DNAemia was significantly higher in sepsis than in all other groups. Primary infection in the hospital and high IL10 levels might favour EBV and CMV reactivation. Conclusion: In this cohort of ICU patients, phenotypic differences were observed between TTV and herpesviruses DNAemia. The higher prevalence of herpesvirus DNAemia in sepsis hints at further studies that may enable a better in vivo understanding of host determinants of herpesvirus viral reactivation. Furthermore, our data suggest that EBV and TTV may be useful as additional markers to predict clinical deterioration in ICU patients.

Torque Teno Virus load in lung cancer patients correlates with age but not with tumor stage.

BACKGROUND: Torque teno virus (TTV) is a ubiquitous non-pathogenic virus, which is suppressed in immunological healthy individuals but replicates in immune compromised patients. Thus, TTV load is a suitable biomarker for monitoring the immunosuppression also in lung transplant recipients. Since little is known about the changes of TTV load in lung cancer patients, we analyzed TTV plasma DNA levels in lung cancer patients and its perioperative changes after lung cancer surgery. MATERIAL AND METHODS: Patients with lung cancer and non-malignant nodules as control group were included prospectively. TTV DNA levels were measured by quantiative PCR using DNA isolated from patients plasma and correlated with routine circulating biomarkers and clinicopathological variables. RESULTS: 47 patients (early stage lung cancer n = 30, stage IV lung cancer n = 10, non-malignant nodules n = 7) were included. TTV DNA levels were not detected in seven patients (15%). There was no significant difference between the stage IV cases and the preoperative TTV plasma DNA levels in patients with early stage lung cancer or non-malignant nodules (p = 0.627). While gender, tumor stage and tumor histology showed no correlation with TTV load patients below 65 years of age had a significantly lower TTV load then older patients (p = 0.022). Regarding routine blood based biomarkers, LDH activity was significantly higher in patients with stage IV lung cancer (p = 0.043), however, TTV load showed no correlation with LDH activity, albumin, hemoglobin, CRP or WBC. Comparing the preoperative, postoperative and discharge day TTV load, no unequivocal pattern in the kinetics were. CONCLUSION: Our study suggest that lung cancer has no stage dependent impact on TTV plasma DNA levels and confirms that elderly patients have a significantly higher TTV load. Furthermore, we found no uniform perioperative changes during early stage lung cancer resection on plasma TTV DNA levels.

Estimates of Cancer Mortality Attributable to Carcinogenic Infections in Italy.

Several infectious agents are ascertained causes of cancer, but the burden of cancer mortality attributable to carcinogenic infections in Italy is still unknown. To tackle this issue, we calculated the rate and regional distribution of cancer deaths due to infections sustained by seven pathogens ranked as group 1 carcinogenic agents in humans by the International Agency for Research on Cancer. Population attributable fractions related to these agents were applied to annual statistics of cancer deaths coded according to the 10th International Classification of Diseases. The estimated burden of cancer mortality attributable to carcinogenic infections in Italy during the period 2011-2015 was 8.7% of all cancer deaths registered yearly, on average. Approximately 60% of deaths occurred in men, and almost the whole burden was due to four infectious agents (Helicobacter pylori, hepatitis C virus, high-risk human papillomavirus, and hepatitis B virus). The analysis of regional distribution showed a higher number of infection-related cancer deaths in the northern regions, where the estimates reached 30 (Liguria) and 28 (Friuli Venezia Giulia) deaths per 100,000 inhabitants in 2015. Since one-twelfth of cancer deaths were attributable to these modifiable risk factors, the implementation of appropriate prevention and treatment interventions may help to reduce the impact of these infections on cancer mortality.

Torque teno virus viral load is related to age, CMV infection and HLA type but not to Alzheimer's disease.

Torque teno virus (TTV) is an unenveloped, circular, single stranded DNA virus with a genome size of approximately 3.8 kb. Previous studies have demonstrated varying grades of association between TTV DNA levels and immune deficiencies related to age, chronic infections and cancer. Alzheimer's disease (AD) has been related to persistent viral infections such as HSV-1 and CMV, but it is not known whether TTV viral load could serve as a functional biomarker of cellular immunity in this setting. Therefore, the objective of this study was to investigate whether TTV infection and viral load is related to AD status, CMV immunity, systemic inflammation or HLA types connected to anti-viral immunity. A total of 50 AD subjects and 51 non-demented controls were included in the study. AD subjects were diagnosed according to NINCDS-ADRDA and DSM-IV criteria and neuroradiologic findings were consistent with the diagnosis. TTV viral load was analyzed in plasma samples using a quantitative real-time PCR. Using a cut-off for TTV status at 200 copies/ml, 88% (89/101) of the study subjects were classified as TTV positive. TTV viral load significantly increased with age (beta 0.049 per year, p<0.001) but significantly decreased in relation to CMV IgG levels (beta -0.022 per 1000 units, p = 0.005) and HLA-B27 positivity (beta -0.53, p = 0.023). In conclusion, TTV immune control is not significantly affected by AD status, but appears related to age, CMV humoral immune response and HLA type.

Infections with DNA Viruses, Adenovirus, Polyomaviruses, and Parvovirus B19 in Hematopoietic Stem Cell Transplant Recipients and Patients with Hematologic Malignancies.

Infections due to adenovirus, polyomaviruses (BK and JC viruses), and parvovirus B19 may not be as common as infections due to other DNA viruses, such as cytomegalovirus in patients with hematological malignancies and the recipients of hematopoietic stem cell transplantation. However, these infections may result in life-threatening diseases that significantly impact patients' recovery, morbidity, and mortality. Treating physicians should be aware of the diseases associated with these viruses, the patient populations at increased risk for complications due to these infections, and the available diagnostic and therapeutic approaches.

Prevalence of human anelloviruses in Romanian healthy subjects and patients with common pathologies.

BACKGROUND: Human anelloviruses (TTV, TTMDV and TTMV) are at high prevalence all across the globe, having also a controversial disease-inducing potential. This study aimed to estimate the prevalence of anelloviral DNA in the Romanian human population and to investigate the association of infections with common pathologies in Romanian population. METHODS: After informed consent, blood samples were collected from 2000 subjects represented by: clinically healthy individuals (n = 701) and a group of patients with pathologies linked to low grade inflammation or alteration of carbohydrate metabolism (n = 1299). All samples were analysed for the presence of TTV, TTMDV and TTMV DNA by hemi-nested PCR. RESULTS: The prevalence of TTV, TTMDV and TTMV in the studied population was 68.2, 54.4%, respectively 40.1%, lower than the recent reports from other geographic regions. The three viral species were significantly more frequent in the group of patients compared to the healthy subjects and were associated with type 2 diabetes mellitus. The presence of anelloviral DNA was also associated with medical procedures (e.g. haemodialysis/transfusions, surgical procedures) and previous hepatitis A virus infection. Lifestyle choices related to alcohol consumption, smoking, physical activity and living environment were not associated with differences in distribution of the three viruses. CONCLUSION: Further evidence is needed to establish a correlation between infection with human anelloviruses and a pathology or group of pathologies.

Prevalence of occult hepatitis B virus infection and Torque teno virus infection and their association with hepatocellular carcinoma in chronic hepatitis C patients.

BACKGROUND: The role of occult hepatitis B virus (HBV) infection and Torque teno virus (TTV) infection in the development of hepatocellular carcinoma (HCC) in chronic hepatitis C patients is still uncertain. AIM: The aim of the present study was to investigate the prevalence and significance of OBI and TTV infection, and to examine the genetic diversity of these viruses, in chronic hepatitis C patients with and without HCC. METHODS: Sera from 151 hepatitis C virus (HCV)-infected patients (49 patients with HCC and 102 without HCC) negative for HBV surface antigen (HBsAg) were tested for the presence of OBI and TTV infection by semi-nested and group-specific multiplex PCR assays, respectively. Nucleotide sequencing of HBV S region was further performed. RESULTS: OBI and TTV infection were detected in 5 (3.3%) and 68 (45%) patients, respectively. HBV isolates were classified into genotypes A (4/5, 80%) and D (1/5, 20%), and no HBsAg escape mutation was observed. TTV phylogenetic group 3 was the most prevalent among both HCC and non-HCC patients. OBI and TTV infection were significantly more frequent in patients with HCC than patients without HCC (p=0.003, and p=0.009, respectively). Moreover, TTV infection was associated with HCC (OR=2.23, 95%CI=1.04-4.80, p=0.040), independently of liver cirrhosis. CONCLUSIONS: A low prevalence of OBI was observed in patients with HCV-related chronic liver disease, and TTV infection was an independent factor associated with the occurrence of HCC. Whether TTV influences the progression of liver disease in chronic hepatitis C patients remains to be elucidated.

[Non-Helicobacter pylori, Non-nonsteroidal Anti-inflammatory Drug Peptic Ulcer Disease].

Non-Helicobacter pylori, non-NSAID peptic ulcer disease (PUD), termed idiopathic PUD, is increasing in Korea. Diagnosis is based on exclusion of common causes such as H. pylori infection, infection with other pathogens, surreptitious ulcerogenic drugs, malignancy, and uncommon systemic diseases with upper gastrointestinal manifestations. The clinical course of idiopathic PUD is delayed ulcer healing, higher recurrence, higher re-bleeding after initial ulcer healing, and higher mortality than the other types of PUD. Genetic predisposition, older age, chronic mesenteric ischemia, cigarette smoking, concomitant systemic diseases, and psychological stress are considered risk factors for idiopathic PUD. Diagnosis of idiopathic PUD should systematically explore all possible causes. Management of this disease is to treat underlying disease followed by regular endoscopic surveillance to confirm ulcer healing. Continuous proton pump inhibitor therapy is an option for patients who respond poorly to the standard ulcer regimen.

Emerging and changing viral diseases in the new millennium.

Most viral infections encountered in resource-rich countries are relatively trivial and transient with perhaps fever, malaise, myalgia, rash (exanthema) and sometimes mucosal manifestations (enanthema), including oral in some. However, the apparent benignity may be illusory as some viral infections have unexpected consequences - such as the oncogenicity of some herpesviruses and human papillomaviruses. Infections are transmitted from various human or animal vectors, especially by close proximity, and the increasing movements of peoples across the globe, mean that infections hitherto confined largely to the tropics now appear worldwide. Global warming also increases the range of movement of vectors such as mosquitoes. Thus recent decades have seen a most dramatic change with the emergence globally also of new viral infections - notably human immunodeficiency viruses (HIV) - and the appearance of some other dangerous and sometimes lethal infections formerly seen mainly in, and reported from, resource-poor areas especially in parts of Asia, Latin America and Africa. This study offers a brief update of the most salient new aspects of the important viral infections, especially those with known orofacial manifestations or other implications for oral health care.

Mate-Pair Sequencing as a Powerful Clinical Tool for the Characterization of Cancers with a DNA Viral Etiology.

DNA viruses are known to be associated with a variety of different cancers. Human papillomaviruses (HPV) are a family of viruses and several of its sub-types are classified as high-risk HPVs as they are found to be associated with the development of a number of different cancers. Almost all cervical cancers appear to be driven by HPV infection and HPV is also found in most cancers of the anus and at least half the cancers of the vulva, penis and vagina, and increasingly found in one sub-type of head and neck cancers namely oropharyngeal squamous cell carcinoma. Our understanding of HPVs role in cancer development comes from extensive studies done on cervical cancer and it has just been assumed that HPV plays an identical role in the development of all other cancers arising in the presence of HPV sequences, although this has not been proven. Most invasive cervical cancers have the HPV genome integrated into one or more sites within the human genome. One powerful tool to examine all the sites of HPV integration in a cancer but that also provides a comprehensive view of genomic alterations in that cancer is the use of next generation sequencing of mate-pair libraries produced from the DNA isolated. We will describe how this powerful technology can provide important information about the genomic organization within an individual cancer genome, and how this has demonstrated that HPVs role in oropharyngeal squamous cell carcinoma is distinct from that in cervical cancer. We will also describe why the sequencing of mate-pair libraries could be a powerful clinical tool for the management of patients with a DNA viral etiology and how this could quickly transform the care of these patients.

New approaches in vaccine-based immunotherapy for human papillomavirus-induced cancer.

The identification of human papillomavirus as the etiological factor for cervical cancer provides an opportunity to treat these malignancies by vaccination. Although therapeutic vaccination against viral oncogenes regularly induces a specific T cell response, clinical effectivity remains low. Three factors are particularly important for clinical outcome: the balance between cytotoxic T cells and regulatory immune subsets, the balance between cytotoxic T cells and tumor cells and finally the killing efficiency of cytotoxic T cells within the tumor. To improve these three factors, therapeutic vaccination is combined with other treatments. Here, we review those studies that are based on understanding the inhibitory mechanisms that prevent unleashing the full power of therapeutic vaccine-induced T cells and utilize combinatorial interventions based on these insights.

Vivências e necessidades de saúde de homens no período pós-nascimento de um filho / Experiences and health needs of men in the period post-birth of a child / Experiencias y necesidades de salud de los hombres en el período post-nacimiento de un hijo

Esta pesquisa aborda percepções de homens sobre suas experiências e necessidades de saúde no pós-nascimento. Objetiva-se distinguir analiticamente, a partir de uma perspectiva de gênero, necessidades de saúde relativas ao evento, experimentadas, expressas e/ou negadas pelos homens. Trata-se de um estudo exploratório-descritivo, qualitativo, realizado em dois territórios de saúde de Cuiabá, Mato Grosso, mediante entrevista semiestruturada e análise temática dos dados. Participaram oito homens que vivenciavam o pós-nascimento de um filho. Estes manifestaram, sobretudo, a necessidade de provimento de segurança financeira à família, destacando também a necessidade de bem estar do filho, acessando o retorno afetivo que a experiência traz. Não se reconheciam com necessidades de saúde no pós-nascimento. O apoio dos serviços locais de saúde é importante para que os homens se percebam na vivência da paternidade e a sua relação com aspectos socioculturais, para que distingam necessidades próprias, valorizem o cuidado de si e adotem uma perspectiva equânime de gênero.

This research addresses men’s perceptions about their experiences and health needs in the post-birth period. The goal is to distinguish analytically and from a gender perspective the health needs related to the event, experienced, expressed and/or denied by men. This is an exploratory, descriptive and qualitative study carried out in two municipal health areas of Cuiabá, state of Mato Grosso, using a semi structured interview and thematic analysis of the data. The participants were eight men who were experiencing the post-birth period of a child. Above all, they expressed the need to provide financial security to the family, emphasizing also the need of their children’s well-being, with the affective return that this experience brings. They did not perceive themselves with health needs during the post-birth period. The support provided by local health services is important so that men can understand the experience of parenthood and its relationship with social and cultural aspects in order to distinguish their own needs, appreciate self-care, and adopt a gender equity perspective.

Esta investigación aborda las percepciones de hombres acerca de sus experiencias y necesidades de salud en el período postparto. El objetivo es distinguir analíticamente, desde una perspectiva de género, las necesidades de salud relacionadas al evento, experimentadas, expresadas y/o negadas por los hombres. Se trata de un estudio exploratorio, descriptivo y cualitativo llevado a cabo en dos áreas municipales de salud de Cuiabá, Estado de Mato Grosso, mediante entrevista semiestructurada y análisis temático de los datos. Participaron ocho hombres que experimentaban el período postparto de un hijo. Ellos expresaron, sobre todo, la necesidad de proveer seguridad económica a la familia, destacando también la necesidad del bienestar de los hijos, con el retorno afectivo que esa experiencia proporciona. No se reconocían con necesidades de salud en el período postparto. El apoyo de los servicios locales de salud es importante para que los hombres entiendan la experiencia de la paternidad y su relación con aspectos socioculturales, para que distingan las necesidades, valoren el cuidado de sí mismos y adopten una perspectiva de equidad de género.

Papillomaviruses and herpesviruses: who is who in genital tumor development of free-ranging Atlantic bottlenose dolphins (Tursiops truncatus)?

The number of studies addressing neoplasia in marine mammals has recently increased, giving rise to concern whether such lesions could be reflective of an emerging infectious disease. Eight species-specific viruses, seven papillomaviruses (PVs) and two herpesviruses (HVs) have separately been shown to be associated with genital tumors in Atlantic bottlenose dolphins (Tursiops truncatus, Tt): TtPV1-6, as well as HVs provisionally assigned the names DeHV4 and -5 (Delphinid HVs). A definite causal role of these viruses in cell transformation remains to be demonstrated. Concurrent PV- and HV-infection has never been reported in marine mammals. DNA extractions from biopsies of genital tumors derived from 15 free-ranging Atlantic bottlenose dolphins were selected for molecular examination. Polymerase chain reaction (PCR) analyses revealed the presence of DeHV4, while a serological screening using an antibody-based TtPV enzyme-linked immunosorbent assay (ELISA) demonstrated previous and/or current infection of the HV-positive dolphins with at least one TtPV type. Therefore, care must be taken when drawing conclusions about viral causalities in tumor development, since the "hit and run" and other mechanisms have been described for types of both viral families. This study presents the first evidence of marine mammals having a history of PV- as well as HV-infection and discusses the disputed effects of viral co-infection.

No evidence for infection of UK prostate cancer patients with XMRV, BK virus, Trichomonas vaginalis or human papilloma viruses.

The prevalence of specific infections in UK prostate cancer patients was investigated. Serum from 84 patients and 62 controls was tested for neutralisation of xenotropic murine leukaemia virus-related virus (XMRV) Envelope. No reactivity was found in the patient samples. In addition, a further 100 prostate DNA samples were tested for XMRV, BK virus, Trichomonas vaginalis and human papilloma viruses by nucleic acid detection techniques. Despite demonstrating DNA integrity and assay sensitivity, we failed to detect the presence of any of these agents in DNA samples, bar one sample that was weakly positive for HPV16. Therefore we conclude that these infections are absent in this typical cohort of men with prostate cancer.

Prevalência e diversidade genética do torque teno vírus em pacientes com lúpus eritematoso sistêmico em serviço de referência no Mato Grosso do Sul / Prevalence and genetic diversity of torque teno virus in patients with systemic lupus erythematosus in a reference service in Mato Grosso do Sul

Estudos recentes sobre o torque teno vírus (TTV), gênero Anellovirus, permitiram construir a hipótese de que esse vírus pode ser um desencadeante ou tenha algum papel patogênico nas doenças reumáticas autoimunes. OBJETIVOS: Verificar a frequência da infecção pelo TTV em pacientes com lúpus eritematoso sistêmico (LES), e sua diversidade gênica, a existência de correlação entre a infecção pelo TTV e as manifestações clínicas do LES, sua evolução clínica e o perfil sorológico. PACIENTES E MÉTODOS: Foram obtidas 46 amostras de soro de pacientes com LES atendidos no Ambulatório de Reumatologia do Hospital Universitário de Campo Grande (NHU/FAMED/UFMS). Para os controles, utilizaram-se 46 amostras de soro de doadores de sangue. O DNA viral foi extraído das amostras utilizando o QIAamp DNA Blood Mini Kit (QIAGEN, Hilden, Alemanha), e amplificado utilizando a técnica de nested PCR. RESULTADOS: Foi encontrada positividade para o TTV em 17 (37 por cento) dos pacientes lúpicos, e em apenas sete (15,2 por cento) dos controles (teste z, P = 0,03). Não houve correlação entre a infecção pelo TTV, as manifestações clínicas, o perfil sorológico e a evolução clínica dos pacientes avaliados neste estudo. CONCLUSÃO: A presença do TTV nos pacientes com LES necessita ser mais bem compreendida a partir deste estudo inicial.

Recent studies on the torque teno virus (TTV), genus Anellovirus, have allowed formulating the hypothesis that TTV may trigger autoimmune rheumatic diseases or have some pathogenic role in them. OBJECTIVES: To determine the frequency of TTV infection in patients with systemic lupus erythematosus (SLE), the genetic diversity of TTV, the correlation between TTV infection and SLE clinical manifestations, and SLE clinical course and serological profile. PATIENTS AND METHODS:Serum samples were obtained from 46 SLE patients treated at the University-Affiliated Hospital of Campo Grande (NHU/FAMED/UFMS), Brazil. For controls, serum samples were obtained from 46 healthy volunteer blood donors. Viral DNA was extracted from samples using the QIAamp DNA Blood Mini Kit (QIAGEN, Hilden, Germany) and amplified using nested PCR. RESULTS: Positivity for TTV was found in 17 (37 percent) of SLE patients and in only seven (15.2 percent) of the controls (z test, P = 0.03). There was no correlation between TTV infection, SLE clinical manifestations, SLE clinical course, and the serological profile of the patients evaluated. CONCLUSION: Further studies on the presence of TTV in SLE patients are required.

The perinatal infection of cytomegalovirus is an important etiology for biliary atresia in China.

AIMS: The aims of this study were to detect the infection rates of DNA viruses in liver tissue of biliary atresia and to investigate the effect of perinatal infection of cytomegalovirus in biliary atresia. METHODS: A total of 85 liver biopsies (taken during Kasai portoenterostomy) were tested by fluorescence quantitative polymerase chain reaction for DNA viruses (herpes simplex virus [HSV], Epstein-Barr virus [EBV], varicella zoster virus [VZV], cytomegalovirus [HCMV], and adenovirus). Immunocytochemical detection of CMV-pp65 antigenemia assay was used to detect the presence of viral protein in liver samples. Human intrahepatic biliary epithelial cells was infected by the laboratory strain AD169 of HCMV in vitro. RESULTS: Virus DNA was found in the biopsies (51/85 HCMV, 5/85 ADV, 3/85 EBV). The biopsies of 2 patients were tested positive for 2 viruses simultaneously. They include one case of HCMV in combination with ADV and one case of ASV in combination with EBV. CMV-pp65 antigenemia were distributed in hepatocyte, vascular endothelial cell, and biliary duct endothelial cell. The cytopathic effect and apoptosis were observed after HCMVAD169 infected human intrahepatic biliary epithelial cells at 6 days. CONCLUSION: Human intrahepatic biliary epithelial cell is the target cell of HCMV. The etiology of biliary atresia is probably multifactorial. The perinatal infection of HCMV is one of the important etiologies for biliary atresia in China.

Torque teno virus 10 isolated by genome amplification techniques from a patient with concomitant chronic lymphocytic leukemia and polycythemia vera.

An infectious etiology has been proposed for many human cancers, but rarely have specific agents been identified. One difficulty has been the need to propagate cancer cells in vitro to produce the infectious agent in detectable quantity. We hypothesized that genome amplification from small numbers of cells could be adapted to circumvent this difficulty. A patient with concomitant chronic lymphocytic leukemia (CLL) and polycythemia vera (PV) requiring therapeutic phlebotomy donated a large amount of phlebotomized blood to test this possibility. Using genome amplification methods, we identified a new isolate (BIS8-17) of torque teno virus (TTV) 10. The presence of blood isolate sequence 8-17 (BIS8-17) in the original plasma was confirmed by polymerase chain reaction (PCR), validating the approach, since TTV is a known plasma virus. Subsequent PCR testing of plasmas from additional patients showed that BIS8-17 had a similar incidence (~20%) in CLL (n = 48) or PV (n = 10) compared with healthy controls (n = 52). CLL cells do not harbor BIS8-17; PCR did not detect it in CLL peripheral blood genomic deoxyribonucleic acid (DNA) (n = 20). CLL patient clinical outcome or prognostic markers (immunoglobulin heavy chain variable region [IGHV ] mutation, CD38 or zeta-chain associated protein kinase 70 kDa [ZAP-70]) did not correlate with BIS8-17 infection. Although not causative to our knowledge, this is the first reported isolation and detection of TTV in either CLL or PV. TTV could serve as a covirus with another infectious agent or TTV variant with rearranged genetic components that contribute to disease pathogenesis. These results prove that this method identifies infectious agents and provides an experimental methodology to test correlation with disease.

Viral-associated thrombotic microangiopathies.

Thrombotic microangiopathies encompass a group of disorders characterized by microangiopathic hemolytic anemia, thrombocytopenia associated with hyaline thrombi (comprised primarily of platelet aggregates in the microcirculation), and varying degrees of end-organ failure. Many primary (genetic) and secondary etiological predisposing factors have been described-namely pregnancy, autoimmune disorders, cancer, drugs and antineoplastic therapy, bone marrow transplantation/solid organ transplantation, and infections. In the setting of infectious diseases, the association with Shiga or Shiga-like exotoxin of Escherichia coli 0157:h7 or Shigella dysenteriae type 1-induced typical hemolytic uremic syndrome is well known. Recently however, an increasing body of evidence suggests that viruses may also play an important role as trigger factors in the pathogenesis of thrombotic microangiopathies. This is a comprehensive review focusing on the current understanding of viral associated/induced endothelial stimulation and damage that ultimately leads to the development of this life-threatening multisystemic disorder.