Sen Virus Infection and Its Relationship to Transfusion–Associated Hepatitis

Abstract

SEN virus (SEN-VAfter cloning of the hepatitis C virus (HCV) 1 and development of sensitive serologic and molecular assays for this pathogen, a dramatic decline in the incidence of transfusionassociated hepatitis occurred. 2,3 However, approximately 10% of transfusion-associated hepatitis cases 4 and 20% of community-acquired hepatitis cases 5 do not have a defined etiology suggesting the existence of additional causative agents. Hepatitis G virus (HGV), 6 also known as GB virus C (GBV-C), 7 was initially suggested as a causative agent of non-A to E hepatitis, but this was not confirmed in further studies. [8][9][10] The originally described TT virus (TTV), discovered in 1997 by representational difference analysis, was detected in 3 of 5 cases of transfusion-associated hepatitis and was proposed as a potential cause of non-A to E hepatitis. 11 Using TTV primers identical to those reported, non-A to E hepatitis cases and controls in the NIH prospective series were tested but no association with transfusion-associated hepatitis was found. 12 Subsequently, primers to more conserved regions of the TTV genome were used in studies in Japan, and the agent was found in greater than 90% of Japanese blood donors. 13 This further diminished the likelihood that TTV was the cause of transfusion-associated hepatitis and precluded the possibility of a practical screening assay. Other studies have also confirmed the high prevalence of TTV and its lack of association with transfusion-associated hepatitis. 14,15 Recently, a novel DNA virus designated SEN virus (SEN-V) was discovered in the serum of an intravenous drug abuser also infected with human immunodeficiency virus. 16,17 SEN-V was initially described as a single-stranded DNA virus of approximately 3,800 nucleotides. 16 Phylogenetic analysis of SEN-V has shown the existence of 8 strains. 18 Although structurally similar to TTV, SEN-V has less than 55% sequence homology and less than 37% amino acid homology with the TTV prototype. 18 Preliminary studies of SEN-V variants were conducted by Dr. Primi (DiaSorin Inc., Brescia, Italy). The prevalence of 5 SEN-V strains (A, B, H [former C], D, and E) and a consensus sequence designated total SEN-V were measured in various donor and patient populations. It was shown that measuring total SEN-V was not practical because the prevalence in donors was 13% and the rate in all transfused populations exceeded 70%. SENV-B was also excluded as a useful screening assay because it was present in 10% of donors and only 8% of patients with transfusion-associated non-A to E hepatitis. SENV-A and SENV-E were found in low prevalence in donors, but did not appear to be associated with non-A to E hepatitis. In contrast, SENV-D and SENV-H had favorable prevalence ratios being found in less than 1% of donors and more than 50% of transfusion-associated non-A to E cases. These initial polymerase chain reaction (PCR) data were confirmed by cloning and sequencing which showed that SENV-D and SENV-H sequences were found in a high proportion of non-A to E ...

TT virus infection: a novel virus-host relationship

“…While the immune system appears to play a role in controlling virus replication [26,27], the mechanisms by which TTV establishes persistent infection remain unclear. While pre-or peri-natal infection may induce partial immunotolerance, that would not explain how infection with antigenically distinct genotypes of TTV can occur later in life [20,22].…”

“…For example, following the suggestion from the original discoverers of TTV [20], it has been proposed that infection with the prototype genotype 1 strain of TTV may be associated with post-transfusion hepatitis [21]. More recently, infection with the TTV genotypes described as SENV-D and SENV-H was found to be much more prevalent in patients with post-transfusion non-A-E hepatitis than transfused patients without hepatitis (92% compared with 24%) [22]. However, as is typical in TTV research, further work has tended to discount such an association [23,24].…”

A cross-sectional study of SEN virus in liver transplant recipients

“…In preliminary studies, SEN V was reported to be associated with the same transmission risk factors as HCV and HBV; transfusion of blood products and abuse of parenteral illicit drugs. 19,20 Moreover, there was a suggestion of an association with NANE hepatitis. 19 We decided to perform a cross-sectional analysis (i.e., at specific time points) on an unselected sample of our liver transplant recipients for the presence of SEN V. We believed that our patients, who received not only a liver allograft but many blood products in the course of their pretransplantation and posttransplantation care, would be at risk for the transmission of unknown blood-borne viruses.…”

“…19,20 Moreover, there was a suggestion of an association with NANE hepatitis. 19 We decided to perform a cross-sectional analysis (i.e., at specific time points) on an unselected sample of our liver transplant recipients for the presence of SEN V. We believed that our patients, who received not only a liver allograft but many blood products in the course of their pretransplantation and posttransplantation care, would be at risk for the transmission of unknown blood-borne viruses. Moreover, because these patients are immunosuppressed, they would be the most likely group to develop persistent transaminitis of untreated hepatotrophic viral infections.…”

“…Eight genotypes (SEN V:A through H) have been identified. SEN V appears to have a high prevalence among blood transfusion recipients, 19 intravenous drug users, and those coinfected with hepatitis C virus (HCV) or HIV. 20 Furthermore, the incidence of SEN V in some reports appears to be greater in those who develop NANE hepatitis than those who do not, 19 which leads to the suggestion that an association with NANE hepatitis exists.…”