不同人类免疫缺陷病毒感染途径群体中戊型肝炎病毒的流行情况

本研究旨在了解不同人类免疫缺陷病毒(human immunodeficiency virus,HIV)感染途径群体中戊型肝炎病毒(hepatitis E virus,HEV)抗体情况,探讨HEV疫苗接种的必要性。采集HIV感染者的血清或血浆,利用酶联免疫吸附试验(enzyme-linked immunosorbent assay,ELISA)检测HEV IgG抗体、IgM抗体及抗原,荧光定量聚合酶链反应(polymerase chain reaction,PCR)检测HEV核酸,Roche高纯化HIV-1核酸定量检测试剂盒(PCR荧光法)检测HIV感染者的HIV载量。比较分析不同HIV感染途径群体中HEV流行率的差别。结果显示,HIV感染者中HEV IgG抗体的阳性率为37.4%,静脉吸毒、成分献血和传播途径不明HIV感染群体的HEV IgG抗体阳性率分别为49.3%、39.5%和30.4%。HEV核酸荧光PCR检测结果均为阴性。3种HIV感染群体之间HEV IgG抗体阳性率差异无统计学意义(χ~2=2.978,P0.05)。HEV IgG阳性与阴性感染者之间HIV载量差异无统计学意义(P0.05)。结果提示,为保护HIV感染者免受HEV感染,应考虑接种HEV疫苗。     

戊型肝炎病毒血清学诊断研究进展

戊型肝炎病毒被发现后,对其检测方法的研究取得了重大进展。但是,戊型肝炎血清学检测还存在很多问题亟待解决。戊型肝炎病毒抗原特性的研究以及抗原的选择对于诊断试剂至关重要。研发适宜的戊型肝炎抗原并建立背景清晰的戊型肝炎Ig G/Ig M标准品对于诊断试剂的研发及评价具有重要意义。     

Effect of concurrent acute infection with hepatitis C virus on acute hepatitis B virus infection.

OBJECTIVE--To investigate the possible interference with acute hepatitis B virus infection by co-infection with hepatitis C virus. DESIGN--Analysis of stored sera collected for transfusion transmitted viruses study in 1970s. SETTING--Four major medical centres in the United States. PATIENTS--12 recipients of blood infected with hepatitis B virus. MAIN OUTCOME MEASURES--In 1970s, presence of antibodies in hepatitis B virus and raised serum alanine aminotransferase concentration; detection of antibodies to hepatitis C virus with new enzyme linked immunoassays. RESULTS--Five of the 12 patients were coinfected with hepatitis C virus. Hepatitis B surface antigen was first detected at day 59 in patients infected with hepatitis B virus alone and at day 97 in those coinfected with hepatitis C virus (p = 0.01); median durations of antigenaemia were 83 and 21 days respectively (p = 0.05), and the antigen concentration was lower in the coinfected patients. Alanine aminotransferase patterns were uniphasic when hepatitis B virus infection occurred alone (range 479-2465 IU/l) and biphasic in patients with combined acute infection (no value > 380 IU/l; p = 0.0025). Four coinfected recipients developed chronic hepatitis C virus infection. The fifth patient was followed for only four months. CONCLUSIONS--Acute coinfection with hepatitis C virus and hepatitis B virus inhibits hepatitis B virus infection in humans, and onset of hepatitis B may reduce the severity of hepatitis C virus infection but not frequency of chronicity. Alanine aminotransferase concentration showed a biphasic pattern in dual infection.     

Human Borna disease virus infection in Australia: serological markers of infection in multi-transfused patients

Borna disease virus (BDV) causes neurological disease in horses, however, there is no consensus as to the extent or significance of human infection. BDV antigen levels in plasma (BDVpAg) and anti-BDV were measured by ELISAs. Confirmation was by Western blot (WB), immunofluorescence assay (IFA) or BDV-peptide-epitope ELISA. For 42 volunteers psychiatrically-defined as non-depressed (82 samples) neither BDVpAg nor anti-BDV was detected. For 104 patients with diagnosed depression (290 samples) 1 was BDVpAg positive and 5 anti-BDV positive, one epitope-e8 positive and 4 IFA positive, with 96% concordance for repeat samples. No BDVpAg was detected in 214 pregnant women, 2 were anti-BDV positive, one WB-confirmed (p24/p40). For 219 donors 2 were BDVpAg positive with anti-BDV detected in 5 (2.3%) one IFA 1:10, another IFA 1:40/epitope-e8 positive. In multitransfused patients, 3/168 were BDV pAg positive, with 14/168 anti-BDV positive, 1 epitope-e8 positive, 2 WB positive and 1 IFA 1:10. In BDVpAg positive multi-transfused patients there was an elevated risk of transaminitis. In one case, a patient BDV-negative prior to transfusion was BDVpAg positive for several months posttransfusion (associated with transaminitis). These data provide serological evidence, supported by confirmatory assays and repeat-sample concordance, of BDV infection in Australia, particularly in multi-transfused patients.     

Synonymous mutations in the core gene are linked to unusual serological profile in hepatitis C virus infection

The biological role of the protein encoded by the alternative open reading frame (core+1/ARF) of the Hepatitis C virus (HCV) genome remains elusive, as does the significance of the production of corresponding antibodies in HCV infection. We investigated the prevalence of anti-core and anti-core+1/ARFP antibodies in HCV-positive blood donors from Cambodia, using peptide and recombinant protein-based ELISAs. We detected unusual serological profiles in 3 out of 58 HCV positive plasma of genotype 1a. These patients were negative for anti-core antibodies by commercial and peptide-based assays using C-terminal fragments of core but reacted by Western Blot with full-length core protein. All three patients had high levels of anti-core+1/ARFP antibodies. Cloning of the cDNA that corresponds to the core-coding region from these sera resulted in the expression of both core and core+1/ARFP in mammalian cells. The core protein exhibited high amino-acid homology with a consensus HCV1a sequence. However, 10 identical synonymous mutations were found, and 7 were located in the aa(99-124) region of core. All mutations concerned the third base of a codon, and 5/10 represented a T>C mutation. Prediction analyses of the RNA secondary structure revealed conformational changes within the stem-loop region that contains the core+1/ARFP internal AUG initiator at position 85/87. Using the luciferase tagging approach, we showed that core+1/ARFP expression is more efficient from such a sequence than from the prototype HCV1a RNA. We provide additional evidence of the existence of core+1/ARFP in vivo and new data concerning expression of HCV core protein. We show that HCV patients who do not produce normal anti-core antibodies have unusually high levels of anti-core+1/ARFP and harbour several identical synonymous mutations in the core and core+1/ARFP coding region that result in major changes in predicted RNA structure. Such HCV variants may favour core+1/ARFP production during HCV infection.     

Immunology of hepatitis B virus and hepatitis C virus infection

More than 500 million people worldwide are persistently infected with the hepatitis B virus (HBV) and/or hepatitis C virus (HCV) and are at risk of developing chronic liver disease, cirrhosis and hepatocellular carcinoma. Despite many common features in the pathogenesis of HBV- and HCV-related liver disease, these viruses markedly differ in their virological properties and in their immune escape and survival strategies. This review assesses recent advances in our understanding of viral hepatitis, contrasts mechanisms of virus-host interaction in acute hepatitis B and hepatitis C, and outlines areas for future studies.     

Animal models for the study of hepatitis B virus infection

Even with an effective vaccine, an estimated 240 million people are chronically infected with hepatitis B virus(HBV) worldwide. Current antiviral therapies,including interferon and nucleot(s)ide analogues,rarely cure chronic hepatitis B. Animal models are very crucial for understanding the pathogenesis of chronic hepatitis B and developing new therapeutic drugs or strategies. HBV can only infect humans and chimpanzees, with the use of chimpanzees in HBV research strongly restricted. Thus, most advances in HBV research have been gained using mouse models with HBV replication or infection or models with HBV-related hepadnaviral infection. This review summarizes the animal models currently available for the study of HBV infection.     

Apoptosis in hepatitis C virus infection

Infection with hepatitis C virus (HCV) is characterized by inflammatory liver damage and a long viral persistence associated with an increased risk of developing hepatocellular carcinoma. Both in liver damage and in oncogenesis a disturbance of apoptosis has been implicated, although the underlying mechanisms in these apparently opposite processes are incompletely understood. HCV-triggered liver injury is mediated mainly by host immune mechanisms and eventually by direct cytopathic effects of HCV. Recent data shows that caspase activation, either triggered by death ligands, other cytokines, granzyme B or HCV proteins, is considerably upregulated in HCV-infected liver. Interestingly, caspase activation appears to correlate closely with the inflammatory response. Data about the role of single HCV proteins, either in cultured cells or transgenic animals models, however, are contradictory, as both pro- and anti-apoptotic effects have been observed. Nevertheless, apoptosis induction upon HCV infection may critically contribute to liver damage, while inhibition of apoptosis may result in HCV persistence and development of hepatocellular carcinoma.     

Persistent hepatitis C virus infection in vitro: coevolution of virus and host

The virological and cellular consequences of persistent hepatitis C virus (HCV) infection have been elusive due to the absence of the requisite experimental systems. Here, we report the establishment and the characteristics of persistent in vitro infection of human hepatoma-derived cells by a recently described HCV genotype 2a infectious molecular clone. Persistent in vitro infection was characterized by the selection of viral variants that displayed accelerated expansion kinetics, higher peak titers, and increased buoyant densities. Sequencing analysis revealed the selection of a single adaptive mutation in the HCV E2 envelope protein that was largely responsible for the variant phenotype. In parallel, as the virus became more aggressive, cells that were resistant to infection emerged, displaying escape mechanisms operative at the level of viral entry, HCV RNA replication, or both. Collectively, these results reveal the existence of coevolutionary events during persistent HCV infection that favor survival of both virus and host.     

Effect of hepatitis A virus infection on cell metabolism in vitro

Hepatitis A virus (HAV), when inoculated into cultures of the PLC/PRF/5 cell line which produces the surface antigen of hepatitis B virus (HBsAg), showed growth characteristics different from those of other picornaviruses. Antigen of HAV (HAAg) is expressed only about 10 days after infection. No major impact on the overall macromolecular biosynthesis of the host cells is observed. The growth rate of HAV-infected and uninfected cells was comparable, although the plating efficiency of infected cells was lower. Different hormonal factors were tested for their ability to stimulate viral antigen expression. Dexamethasone or prostaglandin E1 added to the culture medium increased HAAg expression; insulin reduced expression. Persistent infection of hepatoma cells by HAV never led to a cytolytic infection. In temperature-shift experiments, an adverse effect on the expression of HAAg and HBsAg was observed. In all experiments, the amounts of HBsAg in HAV-infected cells were reduced. On the whole, no major influence on host-cell metabolism is observed in cells persistently infected with HAV. Cell-mediated immunological response as a mechanism of pathological changes in HAV-infected liver is, therefore, more likely than a cytopathological effect.     

Properties of hepatitis A virus particles produced during infection in vitro

Four types of virus-specific particles with different sedimentation coefficients and buoyant densities in CsCl were shown to be accumulated in hepatitis A virus (strain HAS-15) infected fetal rhesus monkey kidney cells (FRhK-4 line). Unlike the mature virions (155S, 1.34 g/cm3), cell-associated isosedimenting 92 S-particles (buoyant densities of 1.30 and 1.20 g/cm3) proved to be sensitive to lipase action. Particles of all four types were shown to contain similar sets of polypeptides, and, with the exception of "empty" 1.30 g/cm3-particles, appeared to be "full" under the immune electron microscopic examination. The viral RNA was unequivocally identified by the molecular hydridization test only in the mature virions.     

Dynamics of hepatitis B virus infection

Mathematical models of the dynamics of HIV and hepatitis C virus infection have proven to be of great utility in understanding pathogenesis and designing better treatments. Here, we review the state of the art in modeling and interpreting data obtained from hepatitis B virus infected patients treated with antiviral agents.     

Epidemiologic features of hepatitis B virus infection in northern Labrador.

We studied the epidemiologic features of hepatitis B virus (HBV) infection in northern Labrador to determine the prevalence of the infection and to obtain a database to develop a vaccination strategy. The study population included seven communities in which five ethnic groups were represented: Inuit, Innu, mixed Inuit and European ancestry ("settler"), nonnative/nonsettler transient population ("white") and people of Innu-white or Innu-Inuit origin ("mixed"). Blood samples from 2156 people (62% of the area residents) were tested for antibody to HBV core antigen (anti-HBc), HBV surface antigen (HBsAg), HBV e antigen (HBeAg), anti-HBc IgM and antibody to the surface antigen (anti-HBs). The overall crude prevalence rate of HBV seromarkers was 14.7% and the HBsAg carrier rate at least 3.2%; the rates were highest for Inuit (26.4% and 6.9% respectively), followed by settler (10.0% and 1.9% respectively) and Innu (7.6% and 0.4% respectively); the white and mixed groups had the lowest overall rates (2.5% and 3.3% respectively). Although the overall prevalence rates were about the same for the two sexes, the HBsAg carrier rate was higher in males (male:female ratio 1.6:1.0). No HBV carriers were positive for HBeAg or anti-HBc IgM antibody. The rate of exposure to HBV was 4% for those below the age of 20 years and reached a peak for those aged 45 to 54 years (85% for Inuit, 40% for settlers and 37% for Innu). There was also a wide variation in the age-standardized prevalence rates (0% to 27.9%) among the ethnic groups in the seven communities surveyed.     

Immunopathogenesis of hepatitis C virus infection

Hepatitis C virus, a recently identified member of the family Flaviviridae, is an important cause of chronic viral hepatitis and cirrhosis. There are similarities in the nature of the immune response to this pathogen with immunity in other flavivirus and hepatotropic virus infections, such as hepatitis B. However, the high rate of viral persistence after primary hepatitis C infection, and the observation that neutralizing antibodies are not protective, would suggest that there are a number of important differences between hepatitis C, other flaviviruses, and hepatitis B. The phenomenon of quasispecies evolution and other viral factors have been proposed to contribute to immune evasion by hepatitis C virus. In the face of established persistent infection, virus-specific cytotoxic T lymphocytes may exert some control over viral replication. However, these same effectors may also be responsible for the progressive liver damage characteristic of chronic hepatitis C infection. The nature of protective immunity, including the role of innate immune responses early after hepatitis C exposure, remains to be defined.