- Hepatitis C virus research
- Hepatitis B Virus Studies
- Liver Disease Diagnosis and Treatment
- interferon and immune responses
- Mosquito-borne diseases and control
- SARS-CoV-2 and COVID-19 Research
- Viral Infections and Vectors
- HIV Research and Treatment
- Viral Infections and Immunology Research
- Long-Term Effects of COVID-19
- Systemic Lupus Erythematosus Research
- Viral gastroenteritis research and epidemiology
- Immune Response and Inflammation
- RNA regulation and disease
- Animal Virus Infections Studies
- Immune responses and vaccinations
- Cytokine Signaling Pathways and Interactions
- CRISPR and Genetic Engineering
- Malaria Research and Control
- COVID-19 Clinical Research Studies
- HIV/AIDS drug development and treatment
- Hepatitis Viruses Studies and Epidemiology
- Endoplasmic Reticulum Stress and Disease
- Animal Disease Management and Epidemiology
- Viral Infections and Outbreaks Research
The University of Adelaide
2015-2024
Stony Brook University Hospital
2024
National Centre for Infectious Diseases
2023
South Australia Pathology
2008-2020
Centre for Cancer Biology
2010-2020
University of South Australia
2015-2017
University of Bern
2007
University Hospital of Bern
2007
Hanson Institute
2004-2006
The University of Texas Medical Branch at Galveston
1999-2005
Background and Aims: The aim of this study was to determine whether expression hepatitis C virus proteins alters hepatic morphology or function in the absence inflammation. Methods: Transgenic C57BL/6 mice with liver-specific RNA encoding complete viral polyprotein (FL-N transgene) structural (S-N were compared nontransgenic littermates for altered liver function. Results: FL-N transcripts detectable only by reverse-transcription polymerase chain reaction, S-N identified Northern blots....
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a highly infectious virus which responsible for the disease 2019 (COVID-19) pandemic. It increasingly clear that recovered individuals, even those who had mild COVID-19, can suffer from persistent symptoms many months after infection, condition referred to as "long COVID", post-acute sequelae of COVID-19 (PASC), syndrome, or post condition. However, despite plethora research on relatively little known about molecular...
ABSTRACT Hepatitis C virus (HCV) infections represent a global health problem and are major contributor to end-stage liver disease including cirrhosis hepatocellular carcinoma. An improved understanding of the parameters involved in progression is needed develop better therapies diagnostic markers manifestation. To understand dynamics host gene expression resulting from persistent infection, DNA microarray analyses were conducted on livers 10 chimpanzees persistently infected with HCV. A...
ABSTRACT Hepatitis C virus (HCV) initiates translation of its polyprotein under the control an internal ribosome entry site (IRES) that comprises most 341-nucleotide (nt) 5′ nontranslated RNA (5′NTR). A comparative analysis related flaviviral sequences suggested segment for which secondary structure was previously ill defined (domain II, nt 44 to 118) forms a conserved stem-loop is located at border HCV IRES and thus may function in viral translation. This prediction tested by mutational...
Abstract Interferon (IFN) α inhibits hepatitis C virus (HCV) replication both clinically and in vitro ; however, the complete spectrum of interferon-stimulated genes (ISGs) expressed HCV-infected liver or responsible for control HCV have not been defined. To better define ISG expression chronically infected liver, DNA microarray analysis was performed on 9 individuals with chronic (CHC). A total 232 messenger RNAs were differentially regulated CHC compared nondiseased controls. significant...
The interferon-stimulated gene, viperin, has been shown to have antiviral activity against hepatitis C virus (HCV) in the context of HCV replicon, although molecular mechanisms responsible are not well understood. Here, we demonstrate that viperin plays an integral part ability interferon limit replication cell-culture-derived (JFH-1) accurately reflects complete viral life cycle. Using confocal microscopy and fluorescence resonance energy transfer (FRET) analysis, localizes interacts with...
The host protein viperin is an interferon stimulated gene (ISG) that up-regulated during a number of viral infections. In this study we have shown dengue virus type-2 (DENV-2) infection significantly induced viperin, co-incident with production RNA and via mechanism requiring retinoic acid-inducible I (RIG-I). Viperin did not inhibit DENV-2 entry but infectious release was inhibited in expressing cells. Conversely, replicated to higher tires earlier shRNA anti-DENV effect mediated by...
The interferon-induced transmembrane (IFITM) family of proteins have recently been identified as important host effector molecules the type I interferon response against viruses. IFITM1 has a potent antiviral hepatitis C virus (HCV), whereas related members IFITM2 and IFITM3 described to effects broad range RNA Here, we demonstrate that play an integral role in HCV act at level late entry stages infection. We established hepatocytes, localize early endosomes, respectively, well lysosome....
Abstract Zika virus (ZIKV) infection has emerged as a global health threat and of pregnant women causes intrauterine growth restriction, spontaneous abortion microcephaly in newborns. Here we show using biologically relevant cells neural placental origin that following ZIKV infection, there is attenuation the cellular innate response characterised by reduced expression IFN-β associated interferon stimulated genes (ISGs). One such ISG viperin well documented antiviral activity against wide...
We describe an infectious molecular clone of a Japanese genotype 1b strain hepatitis C virus (HCV-N). The molecularly cloned sequence HCV-N was compared with alignments other HCV sequences, leading to the identification 15 unique, nonconservative amino acid substitutions within open reading frame (ORF). These were repaired consensus residue, and infectivity RNA transcribed from assessed by intrahepatic inoculation chimpanzee. Viral first detected in serum this chimpanzee 3 weeks following...
Most patients with human immunodeficiency virus (HIV) who remain CD4+ T-cell deficient on antiretroviral therapy (ART) exhibit marked immune activation. As activation may be mediated by microbial translocation or interferon-alpha (IFN-α), we examined these factors in HIV good poor recovery long-term ART. Messenger RNA levels for 3 interferon-stimulated genes were increased T cells of recovery, whereas did not differ from those healthy controls. Poor was also associated expression markers...
ABSTRACT Dengue virus (DENV) pathogenesis is related to the host responses viral infection within target cells, and therefore, this study assessed intracellular changes in proteins following DENV infection. Two-dimensional gel electrophoresis mass spectrometry identified upregulation of endoplasmic reticulum (ER) chaperone GRP78 K562 cells infection, absence virus-induced cell death. Upregulation DENV-infected was confirmed by immunostaining confocal microscopy Western blot analysis also...
A novel T cell–based ZIKV vaccine, encoding NS1 protein, confers protection against systemic infection.
Cellular factors have important roles in all facets of the flavivirus replication cycle. Deciphering viral-host protein interactions is essential for understanding life cycle as well development effective antiviral strategies. To uncover novel host that are co-opted by multiple flaviviruses, a CRISPR/Cas9 genome wide knockout (KO) screen was employed to identify genes required Zika virus (ZIKV). Receptor Activated Protein C Kinase 1 (RACK1) identified factor ZIKV replication, which confirmed...
Coronavirus disease 2019 (COVID-19) convalescents living in regions with low vaccination rates rely on post-infection immunity for protection against re-infection severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We evaluate humoral and T cell five variants of concern (VOCs) mild-COVID-19 at 12 months after infection ancestral virus. In this cohort, ancestral, receptor-binding domain (RBD)-specific antibody circulating memory B levels are conserved most individuals, yet serum...
The factors that regulate lymphocyte traffic in chronic hepatitis C (CHC) are not completely defined. Interferon (IFN)-inducible T cell α chemoattractant (I-TAC) is a relatively new member of the CXCR3 chemokine ligand family selectively recruits activated cells to sites inflammation. To determine if I-TAC plays role CHC, we investigated expression virus (HCV)-infected liver biopsy material. messenger RNA (mRNA) levels were significantly increased HCV-infected compared with normal liver,...
Host factors play an important role in all facets of the hepatitis C virus (HCV) life cycle and one such host factor is signal transducer activator transcription 3 (STAT3). The HCV core protein has been shown to directly interact with activate STAT3, while oxidative stress generated during replication a replicon-based model also induced STAT3 activation. However, despite these findings precise remains unknown. We have established that actively phosphorylated presence replicating HCV....
Hepatitis C virus (HCV) NS5A is essential for viral genome replication within cytoplasmic complexes and assembly at the lipid droplet (LD) surface, although its definitive functions are poorly understood. We developed approaches to investigate dynamics during a productive infection. report here that motility efficient HCV RNA require microtubule network motor dynein demonstrate both motile relatively static NS5A-positive foci enriched with host factors VAP-A Rab5A. Pulse-chase imaging...