- Hepatitis B Virus Studies
- Hepatitis Viruses Studies and Epidemiology
- Hepatitis C virus research
- Viral gastroenteritis research and epidemiology
- Liver Disease Diagnosis and Treatment
- Liver Disease and Transplantation
- Animal Virus Infections Studies
- Viral Infections and Immunology Research
- HIV Research and Treatment
- Monoclonal and Polyclonal Antibodies Research
- Herpesvirus Infections and Treatments
- Immunotherapy and Immune Responses
- Virus-based gene therapy research
- Microbial infections and disease research
- Liver Diseases and Immunity
- Veterinary medicine and infectious diseases
- Bacteriophages and microbial interactions
- Systemic Lupus Erythematosus Research
- Bacillus and Francisella bacterial research
- SARS-CoV-2 and COVID-19 Research
- Protein purification and stability
- Blood groups and transfusion
- Virology and Viral Diseases
- Cytomegalovirus and herpesvirus research
- Respiratory viral infections research
National Institute of Allergy and Infectious Diseases
2011-2025
National Institutes of Health
2010-2025
Sport Ireland
2024
Defence Science and Technology Laboratory
2020-2021
Royal Veterinary College
2014-2020
Johns Hopkins University
1967-2015
King's College London
2012-2014
University of the Witwatersrand
2013
Groote Schuur Hospital
2013
British Heart Foundation
2012
To clarify the relationship between hepatitis C virus infection and development of hepatocellular carcinoma as sequelae non-A, non-B posttransfusion hepatitis, 231 patients with chronic (96 81 cirrhosis 54 carcinoma) were analyzed for antibody to compared 125 B (50 46 29 carcinoma). Antibody was detected in 89.6%, 86.4% 94.4% hepatitis-related carcinoma, respectively, 6%, 17.4% 34.5% similar diseases related B. A history transfusion documented 52%, 33% 42% anti-hepatitis virus-positive cases...
Viral clearance during hepatitis B virus (HBV) infection has been thought to reflect the destruction of infected hepatocytes by CD8 + T lymphocytes. However, in this study, HBV DNA was shown largely disappear from liver and blood acutely chimpanzees long before peak cell infiltration most disease. These results demonstrate that noncytopathic antiviral mechanisms contribute viral acute purging replicative intermediates cytoplasm covalently closed circular nucleus cells.
Previous studies in hepatitis B virus (HBV)-infected humans and chimpanzees suggest that control of HBV infection involves the cells, effector functions, molecular mediators immune response. The objective current study was to identify, liver acutely HBV-infected chimpanzees, spectrum virus-induced response-related genes regulate infection. results demonstrate does not induce any during entry expansion, suggesting it is a stealth early In contrast, large number T cell-derived...
A novel virus, designated swine hepatitis E virus (swine HEV), was identified in pigs. Swine HEV crossreacts with antibody to the human capsid antigen. is a ubiquitous agent and majority of ≥3 months age herds from midwestern United States were seropositive. Young pigs naturally infected by clinically normal but had microscopic evidence hepatitis, developed viremia prior seroconversion. The entire ORFs 2 3 amplified reverse transcription–PCR sera putative gene (ORF2) shared about 79–80%...
Although the CD4(+)- and CD8(+)-T-cell responses to hepatitis B virus (HBV) are thought be crucial for control of HBV infection, relative contribution each T-cell subset as an effector viral clearance is not known. To examine this question, we monitored course infection in control, CD4-depleted, CD8-depleted chimpanzees. Our results demonstrate that CD8(+) cells main responsible disease pathogenesis during acute they suggest mediated by both noncytolytic cytolytic functions response.
The mechanisms by which hepatitis C virus (HCV) induces chronic infection in the vast majority of infected individuals are unknown. Sequences within HCV E1 and E2 envelope genes were analyzed during acute phase 12 patients with different clinical outcomes. Acute resolving was associated relative evolutionary stasis heterogeneous viral population (quasispecies), whereas progressing correlated genetic evolution HCV. Consistent hypothesis selective pressure host immune system, sequence changes...
Spherical 27-nanometer particles were visualized in stools obtained from hepatitis A patients the acute phase of disease. The particle was serologically specific for this disease, and every patient tested demonstrated a serologic response to antigen. findings suggest that it is etiologic agent A.
DNA polymerase activity was detected in each of eight preparations concentrated human hepatitis B antigen (HBAg) rich Dane particles prepared by high-speed centrifugation antigen-positive plasma and none seven control the same way from HBAg-negative plasma. The incorporation (3)H-thymidine-methyl-5'-triphosphate into dependent on four deoxyribonucleoside triphosphates MgCl(2). Treatment HBAg with nonionic detergent Nonidet P-40 (NP40) more than doubled enzyme activity. Fractionation...
Twenty-two patients who had an episode of transfusion-associated hepatitis not positive for B antigen were examined development antibody to heaptitis A and antigens, cytomegalovirus Epstein-Barr virus. Antibody response the 27-nm virus-like was measured by immune electron microscopy. In none 22 studied did serologic evidence infection with virus develop during study period. Nine responses cytomegalovirus, but it difficult relate these seroconversions their hepatitis. addition, all...
To define the early events that determine outcome of acute hepatitis C virus (HCV) infection, we compared course viremia with peripheral and intrahepatic T cell response cytokine profile in six acutely infected chimpanzees. Three different outcomes were observed after peak viral titers reached: sustained clearance, transient clearance followed by chronic infection persisted at initial titers. The results indicate HCV spread outpaces rapidly induces but is not controlled IFN-α/β; follows...
The identification of the neutralization domains hepatitis C virus (HCV) is essential for development an effective vaccine. Here, we show that hypervariable region 1 (HVR1) envelope 2 (E2) protein a critical domain HCV. Neutralization HCV in vitro was attempted with rabbit hyperimmune serum raised against homologous synthetic peptide derived from HVR1 E2 protein, and residual infectivity evaluated by inoculation HCV-seronegative chimpanzees. source plasma obtained patient (H) during acute...
Previous studies in hepatitis B virus (HBV)-infected humans and chimpanzees suggest that control of HBV infection involves the cells, effector functions, molecular mediators immune response. The objective current study was to identify, liver acutely HBV-infected chimpanzees, spectrum virus-induced response-related genes regulate infection. results demonstrate does not induce any during entry expansion, suggesting it is a stealth early In contrast, large number T cell-derived IFN-γ-regulated...
Abstract Oligodeoxynucleotides (ODN) containing unmethylated CpG dinucleotides within specific sequence contexts (CpG motifs) are detected, like bacterial or viral DNA, as a danger signal by the vertebrate immune system. ODN synthesized with nuclease-resistant phosphorothioate backbone have been shown to be potent Th1-directed adjuvants in mice, but these motifs relatively inactive on primate leukocytes vitro. Moreover, vitro assays that predict vivo adjuvant activity for primates not...
Prior to the recent discovery of swine hepatitis E virus (swine HEV) in pigs from midwestern United States, HEV was not considered endemic this country. Since is antigenically and genetically related human strains HEV, it important characterize new further. The infectivity titer a pool determined order prepare standardized reagent evaluate dose response pigs. Although sequence varied extensively those most very closely two (US-1 US-2) isolated States. U.S. which were recently recovered...
Although antibodies to the hepatitis C virus (HCV) are known be associated with non-A, non-B hepatitis, little is about pattern of HCV replication, its relation antibody levels, and clinical course hepatitis.We measured RNA in serial serum samples from five patients post-transfusion who were followed for 10 14 years after transfusion. We also studied four chimpanzees that experimentally infected these patients. Serum was detected by a "nested" polymerase-chain-reaction (PCR) assay used two...
We have succeeded in constructing a stable full-length cDNA clone of strain H77 (genotype 1a) hepatitis C virus (HCV). devised cassette vector with fixed 5′ and 3′ termini constructed multiple clones single step by cloning the entire ORF, which was amplified long reverse transcriptase–PCR, directly into this vector. The infectivity two complete tested direct intrahepatic injection chimpanzee RNA transcripts. However, we found no evidence for HCV replication. Sequence analysis these 16...
ABSTRACT Hepatitis E virus (HEV) is endemic in many developing and some industrialized countries. It has been hypothesized that animals may be the source of infection. The recent identification swine HEV U.S. pigs demonstration its ability to infect across species have lent credence this hypothesis. To assess potential risk zoonotic infection, we tested a total 468 veterinarians working with (including 389 veterinarians) 400 normal blood donors for immunoglobulin G anti-HEV. Recombinant...
Inoculation of hepatitis B surface antigen (HBsAg)-positive sera from patients with chronic liver disease and intrahepatic delta (δ) into chimpanzees susceptible to infection virus (HBV) resulted in type δ markers (δ antibody δ) recipient animals. A dilution (10-8) serum induced without another HBV-susceptible animal. HBV did not develop animals preexisting titers HBsAg. In circulating HBsAg at the time inoculation, synthesis d occurred earlier its extent duration were greater than...
Hepatitis E may be the most common cause of acute hepatitis in world, occurring primarily developing countries but increasingly recognized developed countries. It can have striking clinical manifestations, including acute-on-chronic liver failure and neurologic complications.
The hepatitis B virus-associated beta antigen was found in the serum of experimentally infected chimpanzee as an internal component a discrete subpopulation surface (HBsAg) particles. 35- to 37-nm particles banded CsCl at 1.24-1.25 g/cm3 and sedimented with mobility intermediate between that virion 22-nm form HBsAg. contained only indistinct structure by electron microscopy were not unique delta agent infection, similar without delta-antigen activity being observed preinfection HBsAg carrier...
In a previous study we sequenced the 5' noncoding (NC) region of 44 isolates hepatitis C virus (HCV) and identified heterogeneous domains that provided evidence for additional genetic groups HCV not previously recognized. this have determined complete nucleotide sequence putative envelope 1 (E1) gene in 51 from around world found they could be grouped into at least 12 distinct genotypes. The E1 8 these genotypes has been reported previously. Although relatedness by analysis NC predicted...