Yuji Hoshi

Non-A, non-B hepatitis specific antibodies directed at host-derived epitope: implication for an autoimmune process

A cDNA clone (GOR47-1) bearing an epitope with an aminoacid sequence GRRGQKAKSNPNRPL (GOR epitope) was isolated from the plasma of a laboratory chimpanzee infected with human non-A, non-B hepatitis (NANBH) agent. The epitope was not encoded by reported sequences of hepatitis C virus (HCV) but instead was coded for by a host cellular sequence. An enzyme-linked immunosorbent assay (ELISA) was developed for antibodies to the GOR epitope (anti-GOR). A patient with acute NANBH produced both IgM and IgG classes of anti-GOR in the acute phase of the illness, with concentrations of IgG class anti-GOR rising when anti-HCV became detectable. Anti-GOR was detected in serum from 59 (81%) of 73 patients with chronic NANBH, 40 (65%) of 62 with NANB liver cirrhosis, and 25 (63%) of 40 NANB patients with primary hepatocellular carcinoma, but in only less than 10% of patients with chronic liver diseases due to hepatitis B virus, alcohol, or an autoimmune disorder, and in only 2% of voluntary blood donors. Circulating HCV-RNA was detected by polymerase chain reaction (PCR) in most patients seropositive for anti-GOR but negative for anti-HCV. Detection of anti-GOR would therefore help in the diagnosis of NANBH and in reducing the occurrence of post-transfusion hepatitis.

Nucleotide sequence of a cloned hepatitis B virus genome, subtype ayr: comparison with genomes of the other three subtypes.

The entire nucleotide sequence of genomic DNA was determined for hepatitis B virus (HBV) of subtype ayr, which had been derived from the blood of a Japanese asymptomatic carrier. The genome was 3215 nucleotides long, and differed in DNA sequence by 10% from that of subtypes adw or ayw, but by only 2% from that of subtype adr. Amino acid sequences coded for by the S, C, P and X genes, as well as by the pre-S region, closely resembled those of subtype adr, indicating that the evolution of HBV/ayr from HBV/adr was more recent than the differentiation of the other three subtypes. In the product of the S gene, the mutually exclusive subtypic determinants of the surface antigen, d and y, were associated with variation of amino acid residues at only the 68th and 122nd positions from the N terminus, in contrast to the variation at as many as seven positions for the other set of subtypic determinants, w and r. Sequences representing high local hydrophilicity in the product of the S gene were involved in subtypic variation, although such sequences in the pre-S region were shared by HBV genomes of the various subtypes. In particular, a hydrophilic sequence of 19 amino acid residues, coded for by the pre-S(2) region and implicated in the presumed hepatotropism of HBV, was possessed in common by HBV/adr, HBV/ayr and HBV/ayw, and differed in HBV/adw by only one residue at the 9th position. This amino acid sequence appears to be a promising candidate for a synthetic peptide vaccine.

Circular Double-Stranded Forms of TT Virus DNA in the Liver

ABSTRACT TT virus (TTV) is an unenveloped, circular, and single-stranded DNA virus commonly infecting human beings worldwide. TTV DNAs in paired serum and liver tissues from three viremic individuals were separated by gel electrophoresis and characterized biophysically. TTV DNAs in sera migrated in sizes ranging from 2.0 to 2.5 kb. TTV DNAs in liver tissues, however, migrated at 2.0 to 2.5 kb as well as at 3.5 to 6.1 kb. Both faster- and slower-migrating forms of TTV DNAs in the liver were found to be circular and of the full genomic length of 3.8 kb. TTV DNAs migrating at 2.0 to 2.5 kb, from either serum or liver tissues, were sensitive to S1 nuclease but resistant to restriction endonucleases, and therefore, they were single-stranded. By contrast, TTV DNAs in liver tissues that migrated at 3.5 to 6.1 kb were resistant to S1 nuclease. They migrated at 3.7 to 4.0 kb after digestion with EcoRI, which suggests that they represent circular, double-stranded replicative intermediates of TTV. When TTV DNAs were subjected to strand-specific primer extension and then amplified by PCR with internal primers, those in serum were found to be minus-stranded DNAs while those in liver tissues were found to be a mixture of plus- and minus-stranded DNAs. These results suggest that TTV replicates in the liver via a circular double-stranded DNA.

An autoantibody cross-reactive to hepatitis C virus core and a host nuclear antigen

GOR, an epitope borne by the amino acid sequence, GRRGQKAKSNPNRPL, is recognized by anti-GOR antibodies specifically found in patients with non-A, non-B hepatitis (NANBH). The epitope is not coded for by the hepatitis C virus (HCV), the presumed causative agent for NANBH, but by a single copy gene of the host. Anti-GOR antibodies, distinct from anti-HCV (c100-3) antibodies, were revealed to have dual specificities; they target both the presumed core gene product of HCV and a host component. This cross recognition is probably derived from homologous regions between the GOR epitope and a viral epitope on the core protein in HCV. It is therefore suggested that anti-GOR is an autoantibody induced by HCV infection. This may explain the autoimmune disease like aspect of NANBH pathogenesis.

Cytomegalovirus (CMV) seroprevalence in Japanese blood donors and high detection frequency of CMV DNA in elderly donors

The current prevalence of cytomegalovirus (CMV) in Japan and the risk of CMV transfusion transmission are unknown in the era of seronegative leukoreduced blood components.

Symptomatic parvovirus B19 infection caused by blood component transfusion.

BACKGROUND: Although a risk of transfusion‐transmitted human parvovirus B19V (TT‐B19V) infection has been a concern, there have been very few reports of clinically relevant TT‐B19V caused by the transfusion of a B19V‐containing blood component. It has therefore been a matter of debate whether a universal B19V screening with an appropriate sensitivity is required.

Unique clinical courses of transfusion‐transmitted hepatitis E in patients with immunosuppression

The high prevalence of specific immunoglobulin G for hepatitis E virus (HEV) in Japanese people raises the possibility of a high incidence of HEV‐viremic blood donors and therefore frequent transfusion‐transmitted HEV (TT‐HEV).

Transfusion-transmitted hepatitis E in a patient with myelodysplastic syndromes

Patients with haematological diseases occasionally exhibit liver dysfunction during treatment. This liver dysfunction can have various causes such as therapy-related drugs and hepatitis B and C infections, although the cause is unclear in some cases. It was recently reported that some patients initially diagnosed with drug-induced liver dysfunction actually had hepatitis E1. Several cases of transfusion-transmitted hepatitis E infections have also been reported1,2. In Japan, screening for hepatitis E does not appear to be performed at the initial examination of patients with acute hepatitis. This might be because hepatitis E is believed to be orally transmitted and to occur mainly in developing countries and rarely in developed countries. However, hepatitis E is a zoonotic infectious disease. Cases of regional endemic hepatitis E virus (HEV) infection have been increasing in Europe, the United States, and Japan1. Although HEV usually causes self-limited acute hepatitis, it sometimes progresses to a chronic infection. Most cases of chronic infection occur in patients undergoing solid organ or haematopoietic stem cell transplantation, in those receiving anti-cancer or immunosuppressant drugs, and in patients with human immunodeficiency virus infection, in whom the condition may progress to liver cirrhosis3. HEV RNA persisted for a long period during treatment in a patient with T-cell lymphoma4. Reactivation of HEV hepatitis was reported after an allogeneic haematopoietic stem cell transplant in a patient with Philadelphia chromosome-positive acute lymphoblastic leukaemia5. On the other hand, a low risk of HEV reactivation after haematopoietic stem cell transplantation was also reported6. More studies on the risk of HEV reactivation are, therefore, required. Here, we report the case of a patient with a myelodysplastic syndrome (MDS) who developed acute hepatitis due to transfusion-transmitted HEV infection. We also review the literature on the topic.

Persistent symptomatic parvovirus B19 infection with severe thrombocytopenia transmitted by red blood cell transfusion containing low parvovirus B19 DNA levels

Transfusion‐mediated human parvovirus B19 (PVB19) infection is rare but often causes severe hematologic disorders. In Japan, routine blood donor screening for PVB19 antigen (detection sensitivity, 106.4 IU/mL) using a chemiluminescent enzyme immunoassay (CLEIA) was introduced in 2008. However, there is no consensus on the minimal infectious dose of PVB19 permissible for red blood cells (RBCs).

Sequence analysis of two variable cytomegalovirus genes for distinction between transfusion‐ and breast milk–transmitted infections in a very‐low‐birthweight infant

Cytomegalovirus (CMV) infections in very‐low‐birthweight infants can lead to serious clinical consequences. When CMV‐related symptoms occur after transfusion, CMV transmission is often attributed to the transfusion products rather than to breast milk. However, it is sometimes difficult to distinguish between transfusion‐transmitted and breast milk–transmitted CMV infections.