[show abstract][hide abstract] ABSTRACT: Nucleotide sequences of hepatitis E virus (HEV) isolates infecting wild boars in Mie prefecture, which is located in the central region of Japan and is far from the most prevalent regions of HEV infection in Japan, were determined and characterized. Among 144 serum samples of wild boars captured in Mie prefecture, 7 were positive for HEV-RNA. The nucleotide sequence of nearly the entire genome was determined for 4 of the 7 positive samples. Phylogenetic tree analyses indicated that 6 samples were subtype 3e and 1 was subtype 3a among the 7 isolates. We identified the indigenization of subtype 3e isolates in Japanese wild boars. Furthermore, 5 subtype 3e isolates were closely related and were located in the peripheral branch of subtype 3e isolates from European countries in the phylogenetic tree. The structure indicated that the ancestor of the 5 subtype 3e isolates originated in Europe. The phylogenetic structure and coalescent analyses suggested that the subtype 3e isolates entered Japan from Europe by importation of large-race pigs around 1966. The results also indicated that several lineages of subtype 3e expanded to a wide area of Japan around 1992 and 1 of the lineages was indigenized in wild boars in Mie prefecture between 1992 and 2009. The appearance of a wild boar cluster in the peripheral branch in the phylogenetic lineage may indicate the direction of gene flow of HEV subtype 3e from swine to wild boars. Clarification of the transmission direction or route should be helpful to prevent a future endemic or epidemic of HEV infection.
Infection, genetics and evolution: journal of molecular epidemiology and evolutionary genetics in infectious diseases 06/2013; · 3.22 Impact Factor
[show abstract][hide abstract] ABSTRACT: Hepatitis E virus (HEV) infection has previously been reported in wild mongooses on Okinawa Island; to date however, only one HEV RNA sequence has been identified in a mongoose. Hence, this study was performed to detect HEV RNA in 209 wild mongooses on Okinawa Island. Six (2.9%) samples tested positive for HEV RNA. Phylogenetic analysis revealed that 6 HEV RNAs belonged to genotype 3 and were classified into groups A and B. In group B, mongoose-derived HEV sequences were very similar to mongoose HEV previously detected on Okinawa Island, as well as to those of a pig. This investigation emphasized the possibility that the mongoose is a reservoir animal for HEV on Okinawa Island.
Journal of Veterinary Medical Science 07/2012; · 0.88 Impact Factor
[show abstract][hide abstract] ABSTRACT: Genetic recombination plays a significant role in the survival and evolution of hepatitis C virus (HCV), but methodological limitations have hindered the exploration of genetic recombination. HCV serotypes were evaluated in 104 patients with chronic hepatitis C when they initially presented in hospitals. Subsequently, HCV genotypes were analyzed using primers for core gene and NS5B gene. Near-complete nucleotide sequences of eight HCV isolates from two suspected patients with 2b/1b recombinant HCV were analyzed by amplification of nine overlapping regions of HCV-specific oligonucleotide primers at different time points: (i) at the first admission; (ii) before and (iii) after interferon therapy; and (iv) after development of hepatocellular carcinoma. The nucleotide sequence of eight HCV isolates obtained was 9,321-9,471 nucleotides in length, comprising a single ORF (polyprotein of 3,014 amino acids.) and segregated into discordant genotypes of 2b and 1b HCV with a recombination junction in NS2. This study highlights the need for more precise characterization of HCV in clinical samples where there is a discrepancy between immunoassays and sequencing. It also demonstrates the circulation of novel inter-genotypic recombinant HCV in Japan, because the cross over point of 2b/1b recombinant HCV in eight clinical isolates of these two patients differed from previously reported HCV recombinant from the Philippines and Japan.
Journal of Medical Virology 07/2012; 84(7):1018-24. · 2.37 Impact Factor
[show abstract][hide abstract] ABSTRACT: Aim: In developed countries including Japan, the transmission route of indigenous hepatitis E virus (HEV) infection is obscure. Accordingly, public health implications of indigenous HEV infection have not been well addressed. The aim of this study was to clarify the route of transmission of a small outbreak of acute hepatitis E and assess the public health implications of indigenous zoonotic HEV transmission. Methods: Three patients with non-A, B and C acute hepatitis, two of whom presented in a critical condition, were assessed for HEV infection using polymerase chain reaction and their route of infection; the genome sequences of the infecting HEV were also analyzed. A phylogenetic tree based on the full, or near full, HEV RNA sequences were constructed by neighbor-joining method. Results: All three patients ingested grilled pork meat and entrails at the same barbecue restaurant in Abashiri, Hokkaido, Japan. When comparing partial to entire, or nearly entire, nucleotide sequences of HEV detected in these patients, they were 99.9-100% identical to each other. These genotype 4 isolates had great resemblance to the genome sequences of the isolates from the mini-outbreak in 2004 in Kitami, a city adjacent to Abashiri. These Kitami/Abashiri strains were segregated into a single cluster on the phylogenetic tree of HEV genotype 4 indigenous to Japan. Conclusion: Indigenous HEV transmission via a zoonotic food-borne route has been demonstrated in Kitami and Abashiri via pork meat and entrails contaminated with virulent HEV strains. Because a similar outbreak can recur in the future, infection sources and distribution routes should be clarified rapidly for public health.
Hepatology Research 03/2012; 42(9):870-8. · 2.07 Impact Factor
[show abstract][hide abstract] ABSTRACT: Since previous studies have investigated the population dynamics of Japan-indigenous genotype 3 hepatitis E virus (HEV) using virus sequences, more nucleotide sequences have been determined, and new techniques have been developed for such analysis.
To prevent future hepatitis E epidemic in Japan, this study aimed to elucidate the cause of past HEV expansion.
The epidemic history of Japan-indigenous genotype 3 HEV was determined using the coalescent analysis framework. Bayesian skyline plot (BSP) and Bayesian estimate of phylogeny with relaxed molecular clock models were calculated using Markov chain Monte Carlo sampling.
Japan-indigenous strains consist of New World strains (subtype 3a), Japanese strains (3b) and European strains (3e). The oldest lineage, 3b, appeared around 1929. Lineages 3a and 3e appeared around 1960. BSPs indicated similar radical population growth of the 3a and 3b lineages from 1960 to 1980.
Population dynamics of the three lineages shared some common characteristics, but had distinguishing features. The appearance of 3a and 3e lineages coincides with the increase of large-race pig importation from Europe and the USA after 1960. The epidemic phase of 3a and 3b strains from 1960 to 1980 could be related to increased opportunity for HEV infection arising from large-scale pig breeding since 1960. Our observations revealed new findings concerning the close relationship between the epidemic history of Japan-indigenous genotype 3 HEV and the improvement of the Japanese pig industry. Infection control in pig farms should be an effective method of preventing HEV infection in humans.
Liver international: official journal of the International Association for the Study of the Liver 12/2011; 32(4):675-88. · 3.87 Impact Factor
[show abstract][hide abstract] ABSTRACT: Hepatitis E is a classic water-borne disease in developing countries. Detection of anti-HEV IgM and IgG antibodies, in addition to HEV RNA are useful epidemiological markers in diagnosis of hepatitis E. This study was conducted to investigate an outbreak of acute viral hepatitis in South-Pakistan. Anti-HEV IgM and IgG were assessed comparatively with serological kits manufactured by Abbott, Cosmic, TGH, and Wantai, selecting HEV RNA as reference assay. Molecular evolutionary analysis was performed by phylogeny and HEV spread time analysis by Bayesian Coalescent Theory approach. Of the 89 patients, 24 (26.9%) did not have acute hepatitis viral marker. Of the remaining 65 cases, 4 (6.1%) were positive for anti-HAV IgM, one (1.5%) for anti-HBc IgM, 2 (3%) for HCV, 53 (81.5%) for anti-HEV IgM, and 5 (7.7%) were hepatitis-negative. The Wantai test was 100% sensitive and specific followed by Cosmic (98.1% and 100%), TGH (98.1% and 97.2%) and Abbott (79.2% and 83.3%). Two HEV variant strains were detected by phylogeny responsible for this acute hepatitis outbreak. Estimates on demographic history of HEV showed that HEV in Pakistan has remained at a steady nonexpanding phase from around 1970 to the year 2005, in which it expanded explosively with the emergence of new HEV variants. In conclusion, the limited sensitivity of available assay (Abbott anti-HEV EIA) may be a concern in HEV diagnosis in Pakistan. This study cautions that the dissemination of the variant strains to other areas of Pakistan may lead to explosive HEV outbreaks.
Journal of Medical Virology 04/2011; 83(4):622-9. · 2.37 Impact Factor
[show abstract][hide abstract] ABSTRACT: The treatment of individuals infected with hepatitis B virus (HBV) is a complex issue in practical settings, despite the explosion of new and effective antiviral agents.
To assess the scope and limitations of ongoing treatment guidelines against HBV from a global perspective.
Present therapeutic guidelines against HBV have been discussed with emphasis on their value in developing countries that harbor about 90% of the total number of global patients who are infected with HBV.
Treatment of HBV-infected patients should be appropriately followed up and healthcare delivery systems should be able to combat treatment-induced adverse side effects. Current therapeutic guidelines should be optimized based on the socio-economic conditions of developing countries.
Expert Opinion on Pharmacotherapy 08/2009; 10(10):1605-14. · 2.86 Impact Factor
[show abstract][hide abstract] ABSTRACT: Hepatitis E virus (HEV) genotype 3, which usually causes asymptomatic infection in Japan, induced severe hepatitis in 8 patients. To better understand genetic features of HEV associated with increased virulence, we determined the complete or near-complete nucleotide sequences of HEV from these 8 patients and from 5 swine infected with genotype 3 strain swJ19. Phylogenetic analysis showed that the isolates from the 8 patients and the 5 swine grouped separately from the other genotype 3 isolates to create a unique cluster, designated JIO. The human JIO-related viruses encoded 18 amino acids different from those of the other HEV genotype 3 strains. One substitution common to almost all human HEV strains in the JIO cluster was located in the helicase domain (V239A) and may be associated with increased virulence. A zoonotic origin of JIO-related viruses is suspected because the isolates from the 5 swine also possessed the signature V239A substitution in helicase.
[show abstract][hide abstract] ABSTRACT: The seroprevalence of hepatitis E virus (HEV) infection in Northeastern Asia is unknown. This study was conducted to gain insight into the epidemiology of HEV that has been obscure in Northeastern China, South Korea and Japan.
A total of 1500 samples of serum were collected (300 each) from 5 groups of inhabitants over 40 years of age (Korean Chinese, indigenous Chinese, South Koreans, Koreans living in Japan, and indigenous Japanese) and screened for antibodies to HEV by the antigen-antibody-antigen sandwich Enzyme Linked Immunosorbent Assay system.
The positivity for HEV antibodies was 50.7% (95%CI: 45.0-56.3) in Korean Chinese, 47.7% (95%CI: 42.1-53.3) in indigenous Chinese, 34% (95%CI: 28.9-39.5) in South Koreans, 14.3% (95%CI: 10.8-18.8) in Koreans living in Japan, and 6.0% (95%CI: 3.8-9.3) in indigenous Japanese.
This result emphasizes that HEV is endemic in Northeastern Asia and tends to accumulate in developing countries. Further studies are needed to elucidate the genotype of HEV circulating in these areas and its transmission route-water-borne outbreaks, smaller outbreaks or sporadic forms attributed to zoonosis-with reference to past epidemics, food culture, and sanitary conditions.
The Journal of infection 03/2009; 58(3):232-7. · 4.13 Impact Factor
[show abstract][hide abstract] ABSTRACT: ALT, alanine aminotransferase: anti-HBs, antibody to HBsAg: APC, Antigen-presenting cell: CHB, Chronic hep- atitis B: cccDNA, covalently closed circular DNA: CTL, Cytotoxic T lymphocytes: DC, Dendritic cells: HBV, Hep- atitis B virus: HBsAg, hepatitis B surface antigen: HCV, Hepatitis C virus: HBV-TM, HBV transgenic mouse, HIV, Human immune deficiency virus: HSV, Herpes simplex virus: HPV, Human papillomavirus: HBV-TM, HBV trans- genic mouse: IL, Interleukin: IFN, Interferon Key words: Chronic viral infections, Immune responses, Antiviral agents, Dendritic cells, Immune therapy Abstract Chronic viral infections represent major challenges in con- temporary medicine, virology and pharmacology. The virus-bearing hosts are commonly found in every parts of the world and it is extremely difficult to manage these pa- tients. In addition, considerable numbers of these patients develop progressive diseases and severe complications. Fi- nally, most of these patients act as permanent reservoirs of virus. Understandings of viral life cycle during the last decade of 20th century and the first decade of 21st century have allowed development of hundreds of antiviral agents for different diseases. But, the clinical efficacy of these drugs is not yet satisfactory. In addition, virologists have provided conclusive evidences suggesting that eradication of most chronic virus from infected hosts may an unachiev- able goal. In this context, it is essential to develop alterna- tive, novel, and evidence-based therapeutic maneuver for these patients. Manipulation of host immune system may be one of these approaches. We would discuss about scopes, limitations, and strategies for manipulation for controlling of chronic viral infections. The primary function of the host's immune system is to mount responses that protect the individual from various microbial infections including viruses. Host's immune re- sponses also control the spread and virulence of the viruses (1). This is applicable to viruses that cause acute infection. After entering the hosts, these viruses are localized in host's tissues, proliferate and induce antiviral immunity. These cellular events may cause damage and destruction of tissues and the host exhibit features of acute inflammatory dis- eases. However, the viruses are either almost completely eliminated from the hosts or adequately controlled in situ by host's immune systems. However, chronic infection is established by many viruses because the hosts induce im- proper and uncoordinated immune responses against these viruses. Most viruses cause persistent infection by evading the host immune surveillance mechanism. Both virus-re- lated factors and host-dependent factors are primarily re- sponsible for viral persistency in subjects with chronic viral infections.
[show abstract][hide abstract] ABSTRACT: Five cases of transfusion transmission of hepatitis E virus (HEV) have been reported so far. The infection routes of the causative donors remain unclear, however. Also, the progress of virus markers in the entire course of HEV infection has not been well documented.
Nucleic acid testing was performed by real-time reverse transcription-polymerase chain reaction targeting the open reading frame 2 region of HEV. Full-length nucleotide sequences of HEV RNA were detected by direct sequencing.
Lookback study of a HEV-positive donor revealed that the platelets (PLTs) donated from him 2 weeks previously contained HEV RNA and were transfused to a patient. Thirteen relatives including the donor were ascertained to enjoy grilled pork meats together in a barbecue restaurant 23 days before the donation. Thereafter, his father died of fulminant hepatitis E and the other 6 members showed serum markers of HEV infection. In the recipient, HEV was detected in serum on Day 22 and reached the peak of 7.2 log copies per mL on Day 44 followed by the steep increase of alanine aminotransferase. Immunoglobulin G anti-HEV emerged on Day 67; subsequently, hepatitis was resolved. HEV RNA sequences from the donor and recipient were an identical, Japan-indigenous strain of genotype 4. HEV RNA was detectable up to Day 97 in serum, Day 85 in feces, and Day 71 in saliva.
A transfusion-transmitted hepatitis E case by blood from a donor infected via the zoonotic food-borne route and the progress of HEV markers in the entire course are demonstrated. Further studies are needed to clarify the epidemiology and the transfusion-related risks for HEV even in industrialized countries.
[show abstract][hide abstract] ABSTRACT: We investigated the prevalence of antibody against hepatitis E virus (HEV) in Japanese patients with hemophilia.
IgG antibody against HEV was measured in serum of 80 Japanese patients with hemophilia by enzyme-linked immunosorbent assay. The prevalence of HEV antibody was compared with the reported prevalence of HEV antibody in Japanese patients undergoing hemodialysis and in Japanese healthy blood donors. Characteristics of patients and coinfection with other transfusion-transmissible viruses were compared in patients with and without HEV antibody.
Anti-HEV IgG antibody was detected in 13 of 80 patients (16.3%). The prevalence was far higher than that reported in Japanese blood donors (3.7%) and was higher than that in Japanese patients undergoing hemodialysis (9.4%). The patients with HEV antibody were significantly older than those without. HEV antibody was not detected in patients <20 years of age and in patients who had received only virus-inactivated coagulation factors. No association was observed between positivity for anti-HEV antibody and severity of hemophilia or coinfection with other parenterally transmissible viruses.
Our results suggest that the parenteral transmission of HEV may have occurred in Japanese patients with hemophilia via non-virus-inactivated coagulation factors.
[show abstract][hide abstract] ABSTRACT: Aims: Transmission of hepatitis E virus (HEV) from wild boar to humans has been reported, particularly from Japan. We attempted to clarify this issue. Methods: We assessed the IgG class antibodies against HEV (anti-HEV) in serum samples taken from 406 boar living in the Ehime area of western Japan from 2001 to 2004, of which 392 were captured in the wild (wild-caught boar) and 14 had been kept in a breeding farm (bred boar). Results: Anti-HEV positive rate in the bred boar (10/14, 71.4%) was significantly higher than in the wild-caught boar (100/392, 25.5%) (P < 0.001). Of the 392 wild-caught boar, 12 (3.1%) were positive for HEV-RNA, 10 of which were then subjected to phylogenetic analyses by sequencing an 821-nt fragment within ORF1. All the 10 isolates segregated to genotype 3, and eight of them were mutually related to form a cluster. All the eight HEV isolates in this cluster were from the wild-caught boar living in one and the same habitat within the studied area, while the other two independent isolates were from different regions. Conclusion: HEV infection is endemic in wild boar in the Ehime area, and we should regard the wild boar as an important reservoir of HEV.
Hepatology Research 03/2007; 37(3):214-20. · 2.07 Impact Factor