SEN Virus Research Articles

Clinical significance of SEN virus infection in patients on maintenance haemodialysis

The SEN virus (SENV) has been identified as a putative new hepatitis virus. This study was conducted to clarify the clinical significance of SENV infection in patients on haemodialysis. A total of 189 patients on maintenance haemodialysis and 60 healthy controls were enrolled. Of the 189 patients, 154 were followed up for 2 years. SENV DNA (genotypes D and H) was measured by means of polymerase chain reaction. SENV infection was significantly (P=0.012) more prevalent in patients on haemodialysis (38%) than in controls (22%). SENV infection was not associated with the amount of transfusion or duration of haemodialysis, while hepatitis C virus (HCV) infection was significantly associated with both of these factors. Elevation of alanine aminotransferase was significantly associated with HCV, but not with SENV viraemia. Of the 154 patients who were followed up, 63 (41%) remained negative, 34 (22%) gained positivity, 28 (18%) lost it and 29 (19%) remained positive for SENV infection. Episodes of alanine aminotransferase elevation were recorded for 3% of the patients who incurred SENV infection and this rate was similar to that observed in patients who were continuously negative for SENV infection (5%). SENV infection was common in patients on haemodialysis. No evidence was obtained that suggested involvement of the hepatitis virus in the pathogenicity of SENV.

Transfusion-transmitted viruses.

1. Michelle S Wright-Kanuth, PhD CLS(NCA)[⇑][1] 1. is Associate Professor, University of Texas Medical Branch, Galveston TX 2. Linda A Smith, PhD CLS(NCA) 1. is Professor and Graduate Program Director, University of Texas Health Science Center at San Antonio 1. Address for correspondence: Michelle S Wright-Kanuth PhD CLS(NCA), Associate Professor, Department of Clinical Laboratory Sciences, University of Texas Medical Branch, 301 University Boulevard, Galveston, TX 77555-1140. (409) 772-3055, (409) 772-9470 (fax). mskanuth{at}utmb.edu The number and variety of viruses that have been proven to be transmitted by the transfusion of blood and blood products continue to increase. Among the viruses that are familiar to the clinical laboratory scientist are those for which the blood supply is currently tested: human immunodeficiency virus human immunodeficiency virus 1/2 (HIV 1/2), human T-cell lymphotropic virus (HTLV) I and II, hepatitis C virus (HCV), hepatitis B virus (HBV), and, in some cases, cytomegalovirus (CMV). The transmission of West Nile virus (WNV) by both transfusion and transplantation has recently emerged as a concern. Donor testing for WNV was implemented as soon as a test for its detection was approved in the summer of 2003. Additionally, the testing of donor units for hepatitis A virus (HAV) and parvovirus B19 is under review and is likely to be implemented in the near future. Donors who have either resided or traveled in the United Kingdom (UK)or continental Europe for an accumulation of three months between the years 1980 and 1996, or injected bovine insulin from the UK, are deferred from blood donation in the United States (U.S.) because they are considered to be at risk for variant Crutzfeldt-Jakob Disease (vCJD), a form of spongiform encephalopathy that may be transfusion-transmissible. Several other viruses are either transfusion-transmitted or suspected of being so. SEN virus (SEN-V) has recently been investigated in transfusion-associated hepatitis. Transfusion-transmitted virus (TTV), an aptly named viral agent, is prevalent in the donor population and may be associated with chronic alanine aminotransferase… ABBREVIATIONS: AABB = American Association of Blood Banks; ALT = alanine aminotransferase; AMT = aminomethyl trimethyl psoralen; anti-HBc = anti-hepatitis B core antigen; BPV = bovine papillomavirus; BSE = bovine spongiform encephalopathy; CDC = Centers for Disease Control; CJD = Crutzfeldt-Jakob disease; CMV = cytomegalovirus; DMMB = dimethymethylene blue; EBV = Epstein-Barr virus; FDA = Food and Drug Administration; FRALE = fangible anchor length effectors; GBV-C = hepatitis GB virus; GGT = gamma glutamyl transferase; HAV = hepatitis A virus; HbsAg = hepatitis B surface antigen; HBV = hepatitis B virus; HCV = hepatitis C virus; HGV = hepatitis G virus; HHV = human herpes virus; HIV = human immunodeficiency virus; HPV = human papillomavirus; HTLV = human T-cell lymphotropic virus I and II; NAT = nucleic acid testing; NIH = National Institutes of Health; REDS = Retrovirus Epidemiology Donor Study; S-D = solvent-detergent process; SD-FFP = solvent-detergent fresh frozen plasma; SEN-V = SEN virus; TNBP = tri ( n -butyl) phosphate; TTV = transfusion-transmitted virus; UVA = ultraviolet A; vCJD = variant Crutzfeldt-Jakob disease; WNV = West Nile virus. [1]: #corresp-1

1065 Sen virus infection influence the pathological findings in liver, but not affect the incidence of carcinoma

1065 Sen virus infection influence the pathological findings in liver, but not affect the incidence of carcinoma

SEN virus infection in patients with chronic hepatitis C: preferential coinfection with hepatitis C genotype 2a and no effect on response to therapy with interferon plus ribavirin.

To clarify the influence that a recently identified SEN virus (SENV) has on hepatitis C virus (HCV) response to therapy with interferon plus ribavirin, 2 SENV variants, SENV-D and SENV-H, were studied in 100 patients with chronic hepatitis C; 57 of these patients were positive for SENV-D/H DNA, and there were no differences, in clinicopathological features, between patients with and without SENV coinfection. However, patients with SENV coinfection had a higher prevalence of HCV genotype 2a than did those without it. The sustained HCV response rate after combination therapy was comparable between patients with and without SENV coinfection. Of the 57 patients with SENV coinfection, 18 (32%) had a sustained SENV response to combination therapy, and SENV-D had a higher sustained response rate than did SENV-H. These results suggest that SENV has a specific link to HCV genotype 2a and that SENV infection has no apparent effect on coexisting chronic hepatitis C.

Retrospective analysis of non‐A–E hepatitis: Possible role of hepatitis B and C virus infection

In an effort to determine the cause of non-A-E hepatitis, a retrospective study was undertaken on a group of patients with hepatitis but without serological infection markers of hepatitis viruses A-E. A total of 60 patients admitted to Beijing Ditan Hospital during the period of September 1997 and September 1999 were chosen for this study. These patients were diagnosed as either acute or chronic hepatitis, but no serological markers of hepatitis viruses A-E were detected. Since TT virus (TTV), human parvovirus B19 (B19), SEN virus (SENV), and GB virus C/HGV were reported to be associated with hepatitis, attempts were made to detect the presence of these viruses in the sera of patients with non-A-E hepatitis by a nested polymerase chain reaction (nPCR) method. Also, more sensitive nPCR and RT-nPCR methods were used to determine HBV DNA and HCV RNA in these patients. Results derived from these analyses demonstrate that HBV DNA was detected in most of these patients (47/60, 78.3%), suggesting that HBV infection played a major role in occult non-A-E hepatitis and detection of HBV DNA by more sensitive PCR methods such as nPCR should be considered for diagnosis of HBV infection. In addition, HCV RNA was detected in three (5%) of these patients. However, GBV-C (HGV) RNA was not detected, and TTV, B19, and SENV appear not to be associated with non-A-E hepatitis, as the prevalence rates of these viruses in patients with non-A-E hepatitis were similar to those in patients with viral hepatitis A-E. The results from this study indicate that co-infection of TTV or B19 with HBV did not increase the severity of the disease.

A novel DNA virus (SEN) among patients on maintenance hemodialysis: prevalence and clinical importance

A recently discovered DNA virus (SEN) has been assumed to be responsible for posttransfusion hepatitis in humans. Phylogenetic analysis of SEN virus has revealed the existence of 8 different strains. Two of them (SEN virus strain H (SENV-H) and SENV-D) have been described as possible candidate viruses for inducing posttransfusion hepatitis. Until now, it is unclear whether patients on maintenance hemodialysis are on increased risk for acquiring SEN virus. To investigate the prevalence of SENV-H among patients on maintenance hemodialysis and to examine whether special measures have to be taken to prevent nosocomial spreading of the virus. Serum samples derived from 78 chronically hemodialysed patients were examined for SENV-H viremia by seminested polymerase chain reaction. A panel of 226 samples from healthy blood donors served as a control group. The prevalence of SENV-H was determined to be 12.8% (n=10) among patients on maintenance hemodialysis. This is nearly the same prevalence as in healthy blood donors (16.8%; n=38). None of the solely SENV-H-viremic individuals had clinical or biochemical signs of liver disease. Enhanced severity of liver disease could not be observed in patients coinfected with hepatitis C virus and SENV-H. We conclude that SENV-H viremia is widespread among hemodialysis patients. Since no viremic patient had clinical or biochemical signs of liver disease, in our setting the hepatitis-inducing capacity of SENV-H remains unclear. On the basis of our results, at present, we do not regard it as necessary to dialyse SENV-H-viremic patients on separate machines.

Non-A to E hepatitis.

The list of possible hepatotropic viruses continues to grow with the discovery of the GB virus-C, the TT virus and the SEN virus. There is emerging data on the biology of these newly discovered :In spite of continuing research into the pathogenicity of the GB virus-C and the TT virus, definite evidence linking them to acute or chronic liver disease is lacking. The SEN virus was reported in 2000, and although there seems to be an association between virus and transfusion-related hepatitis, more data are awaited before definite conclusions can be drawn. The effect of GB virus-C, the TT virus and the SEN virus co-infection on other viral and non-viral hepatitides has also been studied in some detail. Again, there is no definite evidence so far that these viruses modify other liver diseases. At the present time, diagnostic testing for these viruses does not seem to be warranted outside of clinical studies. The discovery of these viruses, however, paves the way for further research into novel viral agents that infect humans, other among hosts.

Insights into SEN virus prevalence, transmission, and treatment in community-based persons and patients with liver disease referred to a liver disease unit.

To document the prevalence and routes of transmission of SEN virus (SEN-V) in community-based individuals and patients referred to a liver disease unit, stored serum samples obtained from 160 Canadian Inuit and 140 patients with liver disease were tested for SEN-V DNA by polymerase chain reaction. In the community-based population, SEN-V was present in 57 (36%) of 160 persons. SEN-V-positive individuals tended to be younger and were more often male. Liver enzyme levels and serologic markers for hepatitis A and B viruses were similar in SEN-V-positive and SEN-V-negative individuals. SEN-V was present in 30 (21%) of the 140 patients with liver disease. Age, sex, risk factors for viral acquisition, prevalence of symptoms, and liver biochemical and histological findings were similar in SEN-V-positive and SEN-V-negative patients. These results indicate that SEN-V infection is a common viral infection in both healthy individuals and patients with chronic liver disease, that transmission likely occurs via nonparenteral routes, and that SEN-V infection is not associated with higher rates of or more-severe liver disease in persons with preexisting liver disease.

Weak association between SEN virus viremia and liver disease.

Recently, a novel DNA virus designated SEN virus (SEN-V), which is thought to be related to posttransfusion hepatitis, was discovered. The aim of the present study was to clarify the relationship between SEN-V infection and the development of liver disease. We examined SEN-V from the sera of 21 patients with non-B, non-C hepatocellular carcinoma (HCC) and 13 patients with non-B, non-C chronic liver disease (CLD) without HCC who were admitted to our hospital between 1995 and 1997. Thirty-two patients without liver disease served as controls and were also examined for SEN-V. SEN-V DNA was detected by the nested PCR method after extraction of DNA from serum. SEN-V DNA was detected in 74% (25 of 34) of patients with CLD with or without HCC who were negative for both hepatitis B virus surface antigen and anti-hepatitis C virus antibody. SEN-V DNA was detected in 69% (9 of 13) of CLD patients without HCC and in 76% (16 of 21) of HCC patients. The prevalence of SEN-V was no higher in patients with liver disease than in patients without liver disease (24 of 32; 75%). There were no significant differences in age, sex, liver function, history of blood transfusion, or amount of alcohol intake between SEN-V-positive and SEN-V-negative CLD and HCC patients. Genetic analysis suggested that SEN-V is closely related to the TT virus family. SEN-V was detected at almost the same frequency in patients with and without liver disease. SEN-V does not seem to contribute either to the pathogenesis of liver disease or to the development of HCC from chronic liver disease.

High prevalence of a variant of SENV in intravenous drug user HIV-infected patients.

The prevalence, route of transmission, and clinical significance of SEN virus (SENV) infection was evaluated in 715 samples obtained from 150 blood donors, 165 patients infected by HIV, 150 with HCV/HBV infection, 80 with autoimmune diseases, 40 with Primary Immunodeficiency, 40 with sexually transmitted diseases, 40 polytransfused, and from 50 unselected patients. The identification of SENV-DNA was performed by polymerase chain reaction and hybridization, followed by an immunoenzymatic method that identify different SENV strains. SENV-A variant is largely represented among HIV-infected patients, being found in 71% of HIV(+) intravenous drug users and in 26% of individuals that had acquired HIV through sex. A high prevalence of SENV-A was observed also in HIV- polytransfused (27%) or in patients with sexually transmitted diseases (30%). These percentages are significantly higher than those observed in an unselected population and in blood donors. Prevalence of SENV-A is, therefore, high among HIV(+) patients with parental risk of exposure, but this infection does not appear to influence the clinical or immune status of HIV(+) patients.

SEN virus infection does not affect the progression of non-A to -E liver disease.

SEN virus (SEN V) was discovered recently as a potential causative agent of non-A, non-B, non-C, and non-E (non-A to -E) hepatitis. The aim of this study was to obtain information about the prevalence of this virus in Japan and its association with non-A to -E liver disease. Sixty-seven patients hospitalized for non-A to -E liver disease, including hepatocellular carcinoma (19 patients), cirrhosis (7 patients), chronic hepatitis (18 patients), and acute hepatitis (23 patients), were tested, along with 49 blood donors. The patients were admitted to Nihon University Hospital between 1991 and 1998. SEN V DNA was detected by a nested polymerase chain reaction, targeting the 5' untranslated region. SEN V DNA was detected in 14 of 49 (28.6%) blood donors and in 33 of 67 (49.3%) patients with non-A to -E liver disease. The prevalence of SEN V DNA was similar among patients with various liver diseases, including hepatocellular carcinoma (42.1%), cirrhosis (57.1%), chronic hepatitis (55.6%) and acute hepatitis (47.8%) and among blood donors (28.6%). There were no significant differences in the clinical profiles of patients with SEN V DNA-positive or -negative chronic hepatitis, cirrhosis, and hepatocellular carcinoma. Similarly, there were no significant differences in the clinical profiles between patients with SEN V DNA-positive and -negative acute hepatitis. In conclusion, SEN V infection is present among many blood donors and is common in patients with non-A to -E liver disease. There are insufficient data to prove a causal role for SEN virus infection in non-A to -E liver disease.

Association between SEN Virus Infection and Hepatitis C in Japan: T. Umemura, H.J. Alter, E. Tanaka, et al. J. Infect Dis 184:1246–1251, 2001

Association between SEN Virus Infection and Hepatitis C in Japan: T. Umemura, H.J. Alter, E. Tanaka, et al. J. Infect Dis 184:1246–1251, 2001

SEN virus: Response to interferon alfa and influence on the severity and treatment response of coexistent hepatitis C

The SEN virus (SENV) is a recently identified single-stranded, circular DNA virus. A strong association between 2 SENV variants (SENV-D and SENV-H) and transfusion-associated non–A-to-E hepatitis has been reported. To clarify the effect of SENV infection on coexisting chronic hepatitis C and the effect of interferon alfa (IFN-α) therapy on SENV replication, SENV DNA was quantitated by polymerase chain reaction in serum samples from 186 patients with chronic hepatitis C. Thirty-nine of 186 (21%) patients with chronic hepatitis C were positive for SENV DNA. There were no differences in the clinical, virologic and histologic features between patients with and without SENV infection. Eighteen of 102 patients with chronic hepatitis C who received IFN-α were positive for SENV DNA. The sustained response rate for hepatitis C virus (HCV) clearance after IFN-α treatment did not differ significantly between patients with SENV (28%) and without SENV infection (39%). SENV DNA levels decreased during therapy in 15 of 16 patients, and 11 of the 16 patients (69%) had a sustained loss of SENV DNA in response to IFN-α. In coinfected patients, SENV responses to IFN-α were significantly better in those who failed to clear HCV RNA than in those who lost HCV RNA (P = .013). In conclusion, SENV infection was frequently found in patients with chronic hepatitis C. SENV infection had no apparent influence on the severity of HCV-related liver disease or the HCV response to IFN-α. SENV was sensitive to IFN-α therapy and the majority of patients had a sustained virologic response. (HEPATOLOGY 2002;35:953-959.)

The presence of a newly identified infectious agent (SEN Virus) in patients with liver diseases and in blood donors in Japan: M. Shibata, R.Y.H. Wang, M. Yoshiba, et al. J Infect Dis 184:400–404, 2001

The presence of a newly identified infectious agent (SEN Virus) in patients with liver diseases and in blood donors in Japan: M. Shibata, R.Y.H. Wang, M. Yoshiba, et al. J Infect Dis 184:400–404, 2001

Novel variants related to TT virus distributed widely in China.

TTV is a DNA virus with high genetic heterogeneity. To investigate the novel isolates of the virus, blood samples were collected from subjects who lived in various parts of China and suffered from hepatitis or were asymptomatic carriers. Nested PCR was carried out to amplify a 3.2-kb fragment using primers deduced from the prototype TTV (TA278). The ten entire 3.2-kb nt sequences were aligned with isolate TA278, SANBAN, TUS01, and SENV retrieved from GenBank, and a phylogenetic tree was constructed by Neighbor-Joining method. The analysis indicated that five novel variants of the present study have not been described before, and all TTV-related isolates could be classified into three groups. The isolate TCHN-A, B and TUS01 were included in a group, and the remaining novel isolates together with SANBAN and TA278 clustered into another group, while SEN virus formed a distinct group. The genetic distances of the five novel variants were 0.5507-0.8476 to TA278, 0.4635-0.7877 to SANBAN, 0.6064-0.7834 to TUS01 and 0.6936-0.8236 to SENV. Of these novel variants, the ORF1 consisted of 426-772 aa and ORF2 of 141-156 aa. The nt identities of ORF1 and ORF2 between those variants and TA278, SANBAN, and TUS01 were 46.1-60.8 and 48.7-63.6%, and those of aa sequences were only 27.1-52.4 and 28.9-45.5%, respectively. The first 65 aa of ORF1 were rich in arginine and most conserved with homology of 56.5-70.0%. There was a hypervariable region from aa 286 to 403 with merely 17.7-27.0% of identity. Despite a low aa identity between TA278 and the variants, they have similar hydrophilicity profiles of ORF1. There were 2-10 N-glycosylation motifs found in these variants. In conclusion, despite the high divergence, sequences of all these isolates shared common genome organisation, ORF structure, hydrophilicity patterns, and some potential motifs with TTV prototype. It is suggested that various TTV and TTV-related isolates belong to a very large and complex family, which remains to be studied.

Epidemiology and prophylaxis of viral hepatitis: a global perspective.

Viral hepatitis with various forms of acute and chronic liver disease as potential and ultimately fatal sequelae presents a public health problem worldwide. Recent published reports on the global epidemiology and prophylaxis of viral hepatitis were reviewed. With the advances in novel technologies, eight distinct types of hepatitis virus have been described: Hepatitis A, B, C, D, E, G, TT and SEN viruses. Hepatitis A and E viruses are transmitted by the fecal-oral route and do not induce a chronic carrier state. Due to major changes in epidemiology of hepatitis A virus their significance is more pronounced in areas of intermediate endemicity. Since the available hepatitis A vaccine is rather expensive, cost-benefit studies should be performed with emphasis on the area under consideration or specialized vulnerable groups. Parenterally transmitted hepatitis B and C viruses are major causes of chronic liver disease, including cirrhosis, hepatocellular carcinoma and end-stage liver failure. Hepatitis D virus is unable to replicate on its own, it requires an established hepatitis B virus infection to be able to replicate. Since its introduction, hepatitis B vaccine has been widely used leading to a significant decrease in HBV infection in countries with universal vaccination. Hepatitis G and TT viruses have been characterized within the latter part of the past decade but their significance as to the causation of human liver disease has yet to be elucidated. Likewise, the precise impact of the most recently described SEN virus isolated from patients with post-transfusion hepatitis awaits further studies. In the course of this review, we present the situation and focus on research activities emphasizing epidemiology and prevention of the various forms of viral hepatitis.

Prevalence and implication of a newly identified infectious agent (SEN virus) in Taiwan.

To investigate the prevalence and clinical relevance of a recently identified SEN virus (SENV) in Taiwan, 2 SENV variants (SENV-D and SENV-H) were studied in high-risk persons, patients with liver disease, and healthy adults. SENV-D and/or SENV-H (SENV-D/H) infections were more frequent in high-risk groups (54%-90%) and in patients with chronic hepatitis B (41%), hepatitis B-related hepatocellular carcinoma (HCC) (54%), chronic hepatitis C (67%), and hepatitis C-related HCC (76%) than in healthy adults (15%). The prevalence of SENV-D/H infection was comparable between patients with non-A to E fulminant hepatitis (30%) and healthy adults. Most subjects with SENV-D/H infection alone had no or mild hepatitis, and coinfection of SENV-D/H with chronic hepatitis B or C was not associated with increased evidence of liver disease and the risk of HCC. These results suggest that SENV-D/H infection is common in high-risk groups in Taiwan but that SENV-D/H infection is not associated with hepatitis.

Transmission of SEN virus from mothers to their babies.

Sera from 30 women at high risk for infection, one half of which were SEN virus positive (SENV(+)), were collected at delivery to study SENV mother-to child transmission. Thirteen of their babies were positive for at least one SENV strain: one baby was SENV(+) at birth, eight became positive within 6 months from delivery, and four became positive in the following months. Our data indicate that vertical transmission of SENV does occur, presumably, at delivery, but it may not induce persistent viremia. This is supported by the fact that, generally, SENV is not detected at birth, by the high SENV homology in the sequences found in the mothers and in their children, by a lack of other risk factors for infection of the babies, and by the irregular detection of SENV in the follow-up. No clinical events surely linked to SENV infection were found, but transient elevations of alanine aminotransferase were observed in babies followed for a long period of time.

Observation of positive selection within hypervariable regions of a newly identified DNA virus (SEN virus)

To elucidate the evolution of SEN virus (SEN-V), serial sequences of chronically SEN-V-infected patients were analyzed. In the hypervariable regions, non-synonymous substitutions significantly predominated. This could be attributed to positive selection in evading immune surveillance of the hosts and to establish a persistent infection. On the basis of the sequences in the two open reading frames of SEN-V DNA, the rate of synonymous substitutions was 7.32×10 −4 per site per year. Since this rate is close to RNA viruses and higher than other DNA viruses, the SEN-V might be replicated by machinery with poor or no proofreading function.

SEN virus coinfection may reduce hepatitis C treatment efficacy

SEN virus coinfection may reduce hepatitis C treatment efficacy