Rapid increase in total torquetenovirus (TTV) plasma viremia load reveals an apparently transient superinfection by a TTV of a novel group 2 genotype

An apparently transient infection by a superimposed torquetenovirus (TTV) in a subject who already carried three different genotypes of the virus is described. The superinfection induced a rapid increase in the plasma TTV load and a decline in immunocomplexed virus. The superinfecting TTV was a novel group 2 genotype.     

Assessment of prevalence and load of torquetenovirus viraemia in a large cohort of healthy blood donors

ObjectivesTorquetenovirus (TTV) is an emerging marker of functional immune competence with the potential to predict transplant-related adverse events. A large-scale epidemiological study was performed to understand how basal values vary in healthy individuals according to age and gender.MethodsWe tested plasma from 1017 healthy blood donors aged 18–69 years. The presence and load of TTV were determined by a real-time PCR assay. A sub-cohort of 384 donors was tested for anti-cytomegalovirus IgG antibodies, and 100 participants were also tested for TTV viraemia on a paired whole blood sample.ResultsThe overall prevalence of TTV was 65% (657/1017) with a mean (±SD) growth of 5 ± 4% every 10 years of age increase, but stably higher in males (465/690, 67%) than in females (192/327, 59%). Mean (±SD) TTV load was 2.3 ± 0.7 Log copies/mL with no sex difference. TTV viraemia showed modest increases along 10-year age intervals (mean ± SD: 0.3 ± 0.1). TTV viraemia in donors sampled 2 years later remained stable (mean ± SD: 2.3 ± 0.8 versus 2.2 ± 0.7 Log copies between samples). Twenty-six per cent (9/34) of blood donors with TTV-negative plasma scored positive when whole blood was tested, and the donors with positive plasma showed a mean (±SD) 1.4 ± 0.5 Log increase in copy numbers when whole blood was tested.ConclusionsThis study establishes the mean value of TTV viraemia in plasma in healthy blood donors and suggests that ageing causes only minimal increases in TTV viraemia.     

慢性肾衰血透患者TTV检测及其与细胞免疫功能的关系

目的　观察慢性肾衰 (CRF)血液透析 (HD)患者中 ,输血传播病毒 (TTV)的感染与患者细胞免疫功能的关系。方法　应用巢式逆转录 -聚合酶链反应 (RT PCR) ,双抗体夹心ELISA法及流式细胞仪 ,分别检测了 90例CRF血透患者和 12 8例对照组血清TTV DNA ,可溶性白细胞介素 2受体 (sIL 2R)和外周血T淋巴细胞亚群。并随机选择对其中1株TTV的部分基因序列进行测定 ,分析TTV与细胞免疫功能、输血次数、HD时间和肝功能的关系。结果　⑴ 90例CRF血透患者中 ,TTV DNA阳性率为 46 6 7% ,明显高于正常对照组 (P <0 0 0 1) ,与日本报道的TTV DNA序列(AB0 0 8394)相应片段的同源性为 98 5 %。⑵CRF血透患者血清中 ,sIL 2R水平明显高于正常对照组 (P <0 0 1) ;CD3 ,CD4 和CD4 /CD8 T细胞比例明显降低 (P <0 0 1)。⑶TTV DNA阳性率与sIL 2R、输血次数及HD时间呈显著的正相关 (r =0 486 ,P <0 0 1;r =0 .5 86 ,P <0 0 0 1;r =0 492 ,P <0 0 1) ,与CD ,CD4 和CD4 /CD8 T细胞比例呈负相关 (r = 0 476 ,P <0 0 1;r = 0 483,P <0 0 1;r= 0 496 ,P <0 0 1) ,而与年龄、性别及手术史均无显著的差别和相关性。结论　CRF血透患者有严重的TTV感染 ;其高发生率可能与细胞免疫功能明显低下及其与血液紧密接触有关     

Biliary excretion of TT virus (TTV)

A novel DNA virus (TT virus; TTV) was isolated from a patient with post-transfusion hepatitis of unknown etiology. If TTV replicates in the liver, TTV may appear in the bile. In the present study, to clarify whether fecal-oral infection occur via biliary excretion, the presence of TTV DNA was assessed in paired serum and bile samples collected from 28 patients with obstructive jaundice without parenchymal liver disease. TTV DNA was detected by polymerase chain reaction (PCR) using semi-nested primers, and quantified by Real Time Detection PCR (RTD-PCR). The nucleotide sequence of isolates TTV DNAs was also determined and the sequences were compared between serum and bile samples. Among 28 patients, 7 were positive for TTV DNA in both samples, and 3 and 2 were positive in serum and bile respectively. Of 7 patients positive for TTV DNA in both samples, the TTV DNA titer was higher in serum of 4 patients and in bile of 1 patient. Among 7 patients positive for TTV DNA in serum and bile, 6 had the same sequence in both samples. Multiple distinct types of TTV DNA clones were isolated from serum in 2 patients and from bile in 4 patients. In conclusion, TTV DNA is detected frequently in bile from patients with obstructive jaundice, suggesting a fecal-oral route of infection and high prevalence of asymptomatic TTV carriers. TTV DNA was detected only in serum from some patients, suggesting that replication of TTV may occur in other organs as well as in the liver.     

Genetic relationship of Torque Teno virus (TTV) between humans and camels in United Arab Emirates (UAE)

Torque Teno Virus (TTV) species-cross infection has been documented. However, the genetic relationship between human and animal TTV remains uncertain. In this study, genotypic characterization of TTV in different Camel specimens from the United Arab Emirates (UAE) was undertaken for comparison with human UAE TTV. A total of 56 specimens: 34 sera, 14 raw, and 8 pasteurized milk samples were tested for TTV. The results showed that the rate of infection was, 38.2% (13/34), 35.7% (5/14), and 100% (8/8), for the samples of sera, raw, and pasteurized milk respectively. The 5'untranslated region (5'UTR) of 23 clones that were generated from PCR products amplified from Camel samples (three sera, three raw, and two pasteurized milk samples) were subjected to sequence analysis. The camel TTV clones were classified as genotype 11 (47.8%), group 5 (43.5%), and SENV-H or genotype 16 (8.7%) which are among the predominant genotypes found in humans in the UAE. Phylogenetic analysis of representative sequences revealed that the similarity between isolates from camels and humans is 92%-97% for the same genotypes. The data lead to the conclusion that camels and humans share a common source of TTV infection in the UAE.     

中国和日本部分地区TT病毒的检出率及基因亚型 …

目的 比较中国及日本部分地区ＴＴ病毒（ＴＴＶ）感染情况及基因亚型分布特征。方法 采用半巢式－聚合酶链反应（Ｓｅｍｉ－ｎｅｓｔｅｄ ＰＣＲ）检测中国和日本部分慢性丙型肝炎患者及正常人血标本中的ＴＴＶ感染情况,并对阳性产物片段直接进行序列分析。结果 发现中国部分正常人群ＴＴＶ感染率为６４％;慢性丙型肝炎患者ＴＴＶ感染率中国国为６８％,日本为４９．１％,基因亚型分布中国ＴＴＶ Ｇ２ａ＋２ｂ亚型占６０％,     

Torque teno virus (TTV): current status

Torque teno virus (TTV), currently classified into the family Circoviridae, genus Anellovirus, was first found in a patient with non-A-E hepatitis. TTV has a single stranded circular DNA of approximately 3.8 kb. TTVs are extraordinarily diverse, spanning five groups including SANBAN and SEN viruses. Torque teno mini virus (TTMV) with approximately 2.9 kb genome also has wide variants. Recently, two related 2.2- and 2.6-kb species joined this community. Recombinations between variants are frequent. This extensive TTV diversity remains unexplained; it is unclear how TTVs could be viable, and why they require such genetic variation. An unequivocal culture system is still not available. TTVs are ubiquitous in > 90% of adults worldwide but no human pathogenicity of TTV has been fully established. Epidemiological surveys need to specify the variants being studied and clinical targets, and must calibrate the sensitivity of the assay used. Potentially interesting observations include a higher viral load in patients with severe idiopathic inflammatory myopathies, cancer and lupus. Active replication was also found in infants with acute respiratory diseases. TTV/TTMV-related viruses were found in chimpanzees, apes, African monkeys and tupaias, and also in chickens, pigs, cows, sheep and dogs. Experimentally, rhesus monkeys were persistently infected by TTV, but only 1/53 chimpanzees. TTV transcribes three species of mRNAs, 3.0-, 1.2- and 1.0-kb in the ratio of 60:5:35. Recently, at least three mRNAs were shown in chicken anaemia virus. The genomic region -154/-76 contains a critical promoter. TTV seems to have at least three proteins; however, the definite functions of these proteins await further research work.     

Effect of immune modulation on TT virus (TTV) and TTV-like-mini-virus (TLMV) viremia

The present study was designed to investigate how two chronically replicating viruses, TT virus (TTV) and TTV-like mini virus (TLMV), interact with host defence systems. Successive serum samples from three groups of subjects, undergoing modifications of their antiviral defence, were tested by real-time PCR to measure changes in viral titers, and by sequence analyses to indicate whether increases in viremia could be attributed to infection with an unfamiliar strain: 1) in patients receiving immunosuppressants subsequent to kidney transplantation, viral titers tended to increase; 2) in soldiers undergoing extreme training known to cause immunosuppression, insignificant increases in titers were observed; and 3) interferon treatment of patients with hepatitis C virus caused a temporary decrease in TTV and TLMV titers. Increases in viremia were associated only occasionally with the appearance of novel strains. The above results add to knowledge on how these viruses are influenced by the host.     

Relationship of plasma total protein and albumin to total calcium in peregrine falcons (Falco peregrinus)

A significant correlation was found between total calcium and total protein concentration in 124 plasma samples of captive peregrine falcons (r = 0.65; P<0.01). About 42% of the variability in calcium was attributable to the change in the plasma total protein concentration (R2 = 0.417). The correlation between calcium and albumin was significant (r = 0.33; P<0.01), but significantly smaller than the correlation between calcium and total protein (P<0.01). Only 11% of the plasma calcium concentration was attributable to difference in concentration of albumin (R2 = 0.108). An adjustment formula for plasma calcium concentration in the peregrine falcon was derived on the basis of the total protein concentration: Adj.Ca (mmol/1) = Ca (mmol/1) -0.02 Total protein (g/1) + 0.67.     

The entire nucleotide sequences of two distinct TT virus (TTV) isolates (TJN01 and TJN02) remotely related to the original TTV isolates

Summary.  TT virus (TTV) has a wide range of sequence divergence by which it is classified into at least 16 genotypes. A TTV isolate of genotype 12 (TJN01) and another of genotype 13 (TJN02) were sequenced in the entire genome, and compared with the reported TTV isolates. TJN01 and TJN02 had genomic lengths of 3787 and 3794 nucleotides (nt), respectively, which were shorter by 66 and 59 nt than the prototype TTV isolate of genotype 1 (TA278). TJN01 and TJN02 shared the nucleotide sequence with TA278 merely in 53.9% and 55.2%, respectively. They possessed two major open reading frames (ORFs) and the noncoding region with a GC-rich region forming stem-loop structures, which are characteristic of TTV. However, their amino acid sequences in ORF1 were similar to that of TA278 in only 35.4 and 34.0%, respectively; TJN01 was 45.4% similar to TJN02. Comparison with TTV isolates of the same genotype identified hypervariable regions in ORF1 of TJN01 and TJN02, as in the prototype TTV of genotype 1. However, quasispecies were barely observed in them. Furthermore, sequences of hypervariable regions scarcely changed during 2–5.5 years in both TJN01 and TJN02. These results indicate that TTV of genotypes 12 and 13 are much different from the prototype TTV of genotype 1. Received January 24, 2000 Accepted March 22, 2000     

TT virus (TTV) loads associated with different peripheral blood cell types and evidence for TTV replication in activated mononuclear cells

TT virus (TTV) loads associated with the peripheral blood cells of seven patients known to carry the virus in plasma were investigated by real-time PCR. Whereas red cells/platelets were uniformly negative, six and four patients yielded positive peripheral blood mononuclear cells (PBMCs) and polymorphonuclear leukocytes, respectively, but viral titres were generally low. Fractionation of PBMCs into monocyte- and B, T4, and T8 lymphocyte-enriched subpopulations showed no pattern in the viral loads that might suggest the preferential association of TTV to one or more specific cell types. TTV-negative PBMCs absorbed measurable amounts of virus when incubated with infected plasma at 4 degrees C. Furthermore, cultures of TTV-negative phytohaemagglutinin-stimulated PBMCs exposed in vitro to virus-positive plasma and faecal extracts released considerable levels of infectious TTV into the supernatant fluid and the same was true for TTV-positive stimulated PBMCs. These results indicate that, whereas freshly harvested resting PBMCs seem to produce little, if any TTV, stimulated PBMCs actively replicate the virus.     

Assay of total mercury in blood, plasma and erythrocytes by emission spectrometry-induced plasma HF (SEPIHF)

The mercury quantification in blood can be performed by ICPAES after dilution in an ammonia buffer and reduction by sodium borohydride. The proposed method does not need mineralization. The sample is not nebulized in the torch but the mercury vapor, after collection in a reactor vial, is swept into the plasma by the carrier gas (argon) using the described glass apparatus, and quantified at lambda = 253.65 nm.     

Relationships between total and allergen-specific serum IgE concentrations and lung function in young adults

BackgroundPrior studies have shown relationships between serum immunoglobulin E (IgE) and asthma.ObjectiveTo investigate relationships between total and allergen-specific IgE concentrations and lung function in young adults.MethodsMeasurements of total IgE, allergen-specific IgE to 6 common allergens, and spirometry (forced expiratory volume in one second [FEV₁], forced vital capacity [FVC], FEV₁/FVC, and percent change in FEV₁ after bronchodilation) were used to calculate correlations between the logarithmically transformed IgE values and measures of lung function among participants in a birth cohort not selected for risk of allergic disease stratified by current asthma, prior asthma, or no asthma.ResultsThe 428 participants were 51.6% female, 93% white, and 18.4 (standard deviation = 0.6) years old. Forty-eight (11.2%) had current asthma, 55 (12.9%) had a history of asthma, and 325 (75.9%) never had asthma. For males with current asthma, correlations between total IgE and FEV₁% and FVC% were ?0.51 (P = .06) and ?0.70 (P = .005), respectively. For females with current asthma, the only significant correlation was between total IgE and the FEV₁/FVC ratio (?0.55, P = .001). After excluding smokers and individuals without detectable allergen-specific IgE, the negative correlations for both males and females remained statistically significant. The correlations among males or females with prior asthma or no history of asthma were minimal and not statistically significant. The sum of the allergen-specific IgEs showed the same pattern of relationships to lung function as did total IgE.ConclusionOur results show significant negative correlations that vary by gender between both total and allergen-specific IgE and measurements of lung function in young adults with current asthma.     

新型病毒TTV感染的初步探讨

目的　探讨ＴＴＶ病毒在不明原因肝炎中的意义及其所致肝损害的临床特征。方法　套式聚合酶链反应检测血清ＴＴＶ病毒ＤＮＡ并对ＴＴＶ病毒阳性病例进行临床分析。结果　病原不明肝炎中ＴＴＶ 病毒感染率为３８－６ ％ ；均为散发病例，多见于青壮年，男女无差别；症状明显，黄疸常见，血清转氨酶中度升高；肝组织呈汇管区炎症；一般病例预后良好，但合并症易加重病情。结论　ＴＴＶ病毒可以解释病原不明肝炎中的部分病因     

Effects of gradient and load carried on human haemodynamic responses during treadmill walking

This study examined the effects of different loads carried and gradients, on haemodynamic and cardiovascular responses during 45 min of treadmill walking. A group of 20 male endurance-trained athletes [mean maximal oxygen uptake 61.4 (SD 4) ml · kg⁻¹ · min⁻¹] volunteered for this study. The subjects took part in three separate trials. The first involved a backpack weighing 25 kg , the second a 35 kg backpack, and the third trial, unladen, while walking on a treadmill at a speed of 5 km · h⁻¹. The subjects began walking on the treadmill with the randomized load at 0% gradient. After 15 min, the gradient was increased by 5% every 15 min for a total of 45 min. The order of the loads carried was randomized among subjects. No significant differences were noted for all the variables measured attributable to loads between 25 kg and 35 kg. However, significant (P < 0.05) differences were seen for all variables each time the gradient was increased. Cardiac output increased from 11.4 (SD 0.6) l · min⁻¹ at 0% to 13.6 (SD 0.8) l · min⁻¹ at 5% and to 17.6 (SD 1.3) l · min⁻¹ at 10% carrying the 35 kg load. Similarly, lactic acid concentrations in the blood increased from 2.8 (SD 0.2) to 3.1 (SD 0.6) and to 5.3 (SD 1.3) mmol · l⁻¹, respectively. Similar changes were observed for all variables while carrying the 25 kg load. In addition, steady states in oxygen uptake and other physiological variables were obtained throughout the course of the tests. These data suggest that during isodynamic exercise, one of the main factors determining metabolic and haemodynamic responses will be the change in gradient and to a lesser extent, the mass of the load carried. Accepted: 12 May 2000     

Prediction of cytomegalovirus (CMV) plasma load from evaluation of CMV whole-blood load in samples from renal transplant recipients

In a prospective cohort of 82 renal transplant recipients, we evaluated the capacity of the cytomegalovirus (CMV) load in whole blood (WB) to predict the plasma CMV load, aiming to identify active CMV infections by using WB samples only and to deduce a WB threshold. Using quantitative real-time PCR, a total of 1,474 WB samples were assayed, of which 279 were positive for CMV, and 140 out of the 276 paired plasma samples tested positive. Thirty (36.6%) patients presented with at least one positive plasma PCR result, and 21 infection episodes (19 patients) required curative treatment (median follow-up time, 12 months). When the plasma CMV load was >500 copies/ml (n = 70), more than 94% (95% confidence interval, 86.0%, 98.4%) of WB samples had >500 copies/ml. Two prediction models were built: log₁₀ plasma viral load (VL) was calculated as −0.3777 + 0.9342 × log₁₀ WB VL and as −0.3777 + 0.8563 × log₁₀ WB VL for patients with and without treatment, respectively. In the validation sample (578 routine samples), 77.2% of the observed and expected plasma viral loads were concordant (95% confidence intervals, 73.5 and 80.5%). According to the model, the plasma viral load was >500 copies/ml when the WB load was >3,170 or >4,000 copies/ml in patients with or without treatment, respectively. WB seems to be an appropriate candidate for routine CMV monitoring of transplant recipients by using a single assay.     

“一肾一夹”高血压鼠血清及组织内哇巴因含量及其与血压相关性的研究

目的:探讨内源性哇巴因(EO)在“一肾一夹(1k1c)”高血压模型血压升高中的作用及其分泌特点。方法:采用酶联免疫吸附试验(ELISA)测定“1k1c”高血压大鼠血清及多种组织内EO含量的改变,并对体内EO含量与大鼠血压进行相关性分析。结果:“1k1c”高血压鼠血清及心脏、肾脏、肾上腺、垂体及下丘脑内EO含量均高于正常大鼠;尤以肾上腺及下丘脑内EO含量最高;其中血清、肾脏及下丘脑内EO含量与大鼠血压呈显著正相关。结论:EO含量增加可能在“1k1c”模型高血压的发生机制中发挥着较为重要的作用;肾上腺可能是EO的来源之一。