A5017279608- HIV Research and Treatment
- HIV/AIDS drug development and treatment
- RNA Research and Splicing
- Virus-based gene therapy research
- RNA Interference and Gene Delivery
- Immune Cell Function and Interaction
- CRISPR and Genetic Engineering
- Mosquito-borne diseases and control
- Viral Infections and Vectors
- RNA and protein synthesis mechanisms
- Bacteriophages and microbial interactions
- Cancer-related gene regulation
- HIV/AIDS Research and Interventions
- Animal Disease Management and Epidemiology
- Virology and Viral Diseases
- Venomous Animal Envenomation and Studies
- Nuclear Structure and Function
- Epigenetics and DNA Methylation
- T-cell and Retrovirus Studies
- Nicotinic Acetylcholine Receptors Study
- Herpesvirus Infections and Treatments
- Cytomegalovirus and herpesvirus research
- Plant Virus Research Studies
- interferon and immune responses
- Reproductive tract infections research
QIMR Berghofer Medical Research Institute
2015-2024
The University of Queensland
2002-2024
Australian e-Health Research Centre
2022-2024
Griffith University
2007-2015
Office of Infectious Diseases
2009
Royal Children's Hospital
1999-2003
Australian Centre for HIV and Hepatitis Virology Research
2001-2003
The University of Texas Southwestern Medical Center
1994-1998
University of California, Los Angeles
1988-1990
Human immunodeficiency virus type 1 (HIV-1) gene expression is modulated by both viral and cellular factors. A regulatory element in the HIV-1 long terminal repeat known as TAR, which extends from nucleotides -18 to +80, critical for activation of transactivator protein, Tat. RNA transcribed TAR forms a stable stem-loop structure serves binding site Tat Although activation, role that DNA plays regulating not clear. Several studies have demonstrated can bind proteins, such UBP-1/LBP-1,...
The movement of proteins between the cytoplasm and nucleus mediated by importin superfamily is essential to many cellular processes, including differentiation development, critical disease states such as viral oncogenesis. We recently developed a high-throughput screen identify specific general inhibitors protein nuclear import, from which ivermectin was identified potential inhibitor α/β-mediated transport. In present study, we characterized in detail transport inhibitory properties...
Five regions of the human immunodeficiency virus type 1 (HIV-1) long terminal repeat (LTR) have been shown to be important in transcriptional regulation HIV HeLa cells. These include negative regulatory, enhancer, SP1, TATA, and TAR regions. Previous studies which purified SP1 was used showed that three SP1-binding sites LTR were vitro transcription this promoter. However, no ascertain role each these basal tat-induced activation vivo reported. To determine vivo, subjected oligonucleotide...
There is increasing evidence that lipoproteins of Treponema pallidum and Borrelia burgdorferi are key inflammatory mediators during syphilis Lyme disease. A principal objective the present study was to identify more precisely similarities divergences among lipopolysaccharide (LPS)- lipoprotein-lipopeptide-induced immune cell signaling events. Like LPS, purified native B. OspA synthetic analogs OspA, OspB, two T. (Tpp47 Tpp17) all induced NF-kappa B translocation in THP-1 human monocytoid...
Cellular proteins have been implicated as important for HIV-1 reverse transcription, but whether any are transcription complex (RTC) cofactors or affect indirectly is unclear. Here we used protein fractionation combined with an endogenous assay to identify cellular that stimulated late steps of in vitro. We identified 25 active fraction, and here show the eEF1A eEF1G subunits eukaryotic elongation factor 1 (eEF1) components RTC. were fractionated human T-cell lysates cofactors, their removal...
Prey-selective venoms and toxins have been documented across only a few species of snakes. The lack research in this area has due to the absence suitably flexible testing platforms. In order test more for prey specificity their venom, we used an innovative taxonomically flexible, high-throughput biolayer interferometry approach ascertain relative binding 29 α-neurotoxic from African Asian elapid representatives (26 Naja spp., Aspidelaps scutatus, Elapsoidea boulengeri, four locales...
Herein we describe a mutant of the two-exon HIV-1 Tat protein, termed Nullbasic, that potently inhibits multiple steps replication cycle. Nullbasic was created by replacing entire arginine-rich basic domain wild type with glycine/alanine residues. Like similarly mutated one-exon mutants, exhibited transdominant negative effects on Tat-dependent transactivation. However, unlike previously reported discovered also strongly suppressed expression unspliced and singly-spliced viral mRNA, an...
The binding of compounds to nicotinic acetylcholine receptors is great interest in biomedical research. However, progress this area hampered by the lack a high-throughput, cost-effective, and taxonomically flexible platform. Current methods are low-throughput, consume large quantities sample, or limited which targets can be tested. We describe novel assay utilizes label-free bio-layer interferometry technology, combination with adapted mimotope peptides, order measure ligand orthosteric site...
Plasminogen activator inhibitor-2 (PAI-2) is well documented as an inhibitor of the extracellular serine proteinase urokinase-type plasminogen (uPA) and expressed in activated monocytes macrophages, differentiating keratinocytes, many tumors. Here we show that PAI-2 has a novel intracellular function retinoblastoma protein (Rb)-binding protein. colocalized with Rb nucleus inhibited turnover Rb, which led to increases levels Rb-mediated activities. Although contains LXCXE motif, binding was...
ABSTRACT The ability of self-replicating RNA (replicon) vaccine vectors derived from the Australian flavivirus Kunjin (KUN) to induce protective αβ CD8 + T-cell responses was examined. KUN replicons encoding a model immunogen were delivered by three different modalities: (i) as naked transcribed in vitro, (ii) plasmid DNA constructed allow vivo transcription replicon cellular polymerase II (DNA based), and (iii) encapsidated into virus-like particles. A single immunization with any these...
Syphilitic genital ulcers are cofactors for the bidirectional transmission of human immunodeficiency virus (HIV). U937 promonocytic cells chronically infected with HIV-1 (U1 cells) or transiently transfected wild type mutant HIV long terminal repeat (LTR) reporter constructs were used to examine mechanisms that likely underlie Treponema pallidum-induced immune cell activation and consequent induction HIV. Virulent T. pallidum, a representative native treponemal lipoprotein (NTp47), synthetic...
Abstract Background The interferon (IFN)-induced, dsRNA-dependent serine/threonine protein kinase, PKR, plays a key regulatory role in the IFN-mediated anti-viral response by blocking translation infected cell phosphorylating alpha subunit of elongation factor 2 (eIF2). human immunodeficiency virus type 1 (HIV-1) evades IFN through binding one its major transcriptional proteins, Tat, to PKR. HIV-1 Tat acts as substrate homologue for enzyme, competing with eIF2α, and inhibiting translational...
Human T-cell leukemia virus types I (HTLV-I) and II (HTLV-II) are human retroviruses which normally infect T-lymphoid cells. HTLV-I infection is associated with adult leukemia-lymphoma, HTLV-II an indolent form of hairy-cell leukemia. To identify potential transcriptional regulatory elements these two related retroviruses, we performed DNase footprinting both the long terminal repeats (LTRs) by using extracts prepared from uninfected T cells, transformed HeLa Five regions LTR three showed...
ABSTRACT Arginine methylation of human immunodeficiency virus type 1 (HIV-1) Tat protein downregulates its key function in viral-gene transactivation. The fate methylated is unknown, so it unclear whether degraded or persists the cell for additional functions. Here we show that arginine methyltransferase PRMT6 increases half-life by 4.7-fold. stabilization depends on catalytic activity and requires within basic domain. In contrast, HIV-1 Rev, which also PRMT6, completely refractory to...
The eukaryotic translation factor eEF1A assists replication of many RNA viruses by various mechanisms. Here we show that down-regulation restricts the expression viral genomic and release infectious virus, demonstrating a biological requirement for in respiratory syncytial virus (RSV) life cycle. key proteins replicase/transcriptase complex RSV; nucleocapsid (N) protein, phosphoprotein (P) matrix (M) all associate with RSV infected cells, although N is strongest binding partner. Using...