A5073797688- HIV Research and Treatment
- Immune Cell Function and Interaction
- T-cell and B-cell Immunology
- Monoclonal and Polyclonal Antibodies Research
- HIV/AIDS drug development and treatment
- SARS-CoV-2 and COVID-19 Research
- Hepatitis C virus research
- Animal Disease Management and Epidemiology
- Hepatitis B Virus Studies
- Vector-Borne Animal Diseases
- Immunotherapy and Immune Responses
- HIV/AIDS Research and Interventions
- Animal Virus Infections Studies
- Glycosylation and Glycoproteins Research
- SARS-CoV-2 detection and testing
- T-cell and Retrovirus Studies
- COVID-19 Clinical Research Studies
- Bacteriophages and microbial interactions
- RNA and protein synthesis mechanisms
- Animal health and immunology
- interferon and immune responses
- RNA Interference and Gene Delivery
- Viral Infections and Immunology Research
- Immunodeficiency and Autoimmune Disorders
- Mosquito-borne diseases and control
Burnet Institute
2014-2024
The University of Melbourne
2013-2023
Peter Doherty Institute
2014-2023
Royal Perth Hospital
2012
The University of Western Australia
2012
National Institute of Allergy and Infectious Diseases
2000-2004
Office of Research Services
2001-2002
National Cancer Institute
2001
National Institutes of Health
2001
St Vincents Institute of Medical Research
1993-2000
Retroviral entry into cells depends on envelope glycoproteins, whereby receptor binding to the surface-exposed subunit triggers membrane fusion by transmembrane protein (TM) subunit. We determined crystal structure at 2.5-Å resolution of ectodomain gp21, TM from human T cell leukemia virus type 1. The gp21 fragment was crystallized as a maltose-binding chimera, and domain used solve initial phases method molecular replacement. comprises an N-terminal trimeric coiled coil, adjacent...
Effective immunity to HIV is poorly understood. In particular, a role for antibody-dependent cellular cytotoxicity (ADCC) in controlling controversial. We hypothesized that significant pressure from HIV-specific ADCC would result immune-escape variants. A series of epitopes HIV-infected subjects specific consensus strain peptides were mapped using flow cytometric assay natural killer cell activation. then compared the responses same peptide epitope derived concurrent sequence(s) expressed...
Abstract A highly protective vaccine will greatly facilitate achieving and sustaining malaria elimination. Understanding mechanisms of antibody-mediated immunity is crucial for developing vaccines with high efficacy. Here, we identify key roles in humoral Fcγ-receptor (FcγR) interactions opsonic phagocytosis sporozoites. We a major role neutrophils mediating phagocytic clearance sporozoites peripheral blood, whereas monocytes contribute minor role. Antibodies also promote natural killer cell...
Two rat calcitonin receptor isoforms have been identified by cDNA cloning from a hypothalamic library. The clones, C1a and C1b, specified proteins of 478 515 amino acids, respectively. clones were identical, except that the C1b sequence encoded 37-amino acid insert in second extracellular domain, which conferred altered ligand recognition. Compared to receptor, expressed receptors exhibited decreased affinity for porcine CT, relative salmon negligible human CT. Clone mRNA was predominately...
Abstract Ab-dependent cellular cytotoxicity (ADCC) Abs stimulate NK cell effector functions and play a role in protecting from controlling viral infections. We characterized ADCC cross-sectional cohort of 80 HIV-infected subjects not on antiretroviral therapy. analyzed response by killing fluorescently labeled target cells, as well expression IFN-γ the degranulation marker CD107a activated cells measured novel intracellular cytokine assay. HIV-specific directed toward Envelope proteins were...
Studying HIV-infected individuals who control HIV replication (elite controllers [ECs]) enables exploration of effective anti-HIV immunity. Env-specific and non-Env-specific antibody-dependent cellular cytotoxicity (ADCC) may contribute to protection from progressive infection, but the evidence is limited. We recruited 22 ECs matched them with 44 viremic subjects. Env- Vpu-specific ADCC responses in sera were studied using a novel enzyme-linked immunosorbent assay (ELISA)-based dimeric...
A vaccine that prevents hepatitis C virus (HCV) infection is urgently needed to support an emerging global elimination program. However, development has been confounded because of HCV's high degree antigenic variability and the preferential induction type-specific immune responses with limited potency against heterologous viral strains genotypes. We showed previously deletion three variable regions from E2 receptor-binding domain (Δ123) increases ability human broadly neutralizing antibodies...
The envelope protein (Env) of human immunodeficiency virus type 1 forms homo-oligomers in the endoplasmic reticulum. oligomeric structure Env is maintained after cleavage a Golgi compartment and transport to surfaces infected cells, where incorporation into budding virions takes place. Here, we use biophysical techniques assess valency virion-associated prior fusion activation. Virion-associated oligomers were stabilized by chemical cross-linking detergent extraction purified immunoaffinity...
Abstract Epidermal Langerhans cells (eLCs) uniquely express the C-type lectin receptor langerin in addition to HIV entry receptors CD4 and CCR5. They are among first target encounter anogenital stratified squamous mucosa during sexual transmission. Previous reports on mechanism of transfer T role have been contradictory. In this study, we examined replication langerin-mediated viral by authentic immature eLCs model Mutz-3 LCs. were productively infected with HIV, whereas LCs not susceptible...
Broadly neutralizing antibodies (BnAbs) protect macaques from cell-free simian/human immunodeficiency virus (SHIV) challenge, but their efficacy against cell-associated SHIV is unclear. Virus in format highly infectious, present transmission-competent bodily fluids, and potentially capable of evading antibody-mediated neutralization. The PGT121 BnAb, which recognizes an epitope consisting the V3 loop envelope glycans, mediates antibody-dependent cellular cytotoxicity neutralization...
Natural killer (NK) cells have been suggested to play a protective role in HIV disease progression. One potent effector mechanism of NK is antibody-dependent cellular cytotoxicity (ADCC) mediated by antiviral antibodies binding the FcγRIIIa receptor (CD16) on cells. We investigated cell-mediated ADCC function and presence plasma from 20 HIV-1-infected patients 10 healthy donors. The HIV-positive were divided into two groups: six who controlled viremia for at least 8 y without treatment...
ABSTRACT We developed a real-time PCR to quantify 16S rRNA gene levels in plasma from HIV-infected patients as marker of microbial translocation. The assay uses shrimp nuclease (SNuc) eliminate DNA contamination, giving high sensitivity and low variability. measured HIV correlated significantly with lipopolysaccharide levels.
ABSTRACT Bovine colostrum (first milk) contains very high concentrations of IgG, and on average 1 kg (500 g/liter) IgG can be harvested from each immunized cow immediately after calving. We used a modified vaccination strategy together with established production systems the dairy food industry for large-scale manufacture broadly neutralizing HIV-1 IgG. This approach provides low-cost mucosal HIV preventive agent potentially suitable topical microbicide. Four cows were vaccinated pre- and/or...
A prophylactic vaccine targeting multiple HCV genotypes (gt) is urgently required to meet World Health Organization elimination targets. Neutralizing antibodies (nAbs) and CD4
Human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein (Env) oligomerization was investigated by coexpressing wild-type and truncated glycoproteins to determine the minimum sequence required for mutant-wild-type hetero-oligomerization. The gp41 putative amphipathic alpha-helix, Leu-550 Leu-582, essential hetero-oligomer formation. Alanine substitution of 9 10 residues composing alpha-helix 4-3 hydrophobic repeat inhibit hetero-oligomerization render precursor, gp160, monomeric....
Abstract We present a novel protein crystallization strategy, applied to the of human T cell leukemia virus type I (HTLV‐1) transmembrane gp21 lacking fusion peptide and domain, as chimera with Escherichia coli maltose binding (MBP). Crystals could not be obtained MBP/gp21 in which partners were separated by flexible linker, but after connecting MBP C‐terminal α‐helix predicted N‐terminal α‐helical sequence via three alanine residues. The sequences conferred trimeric structure soluble...
Natural control of HIV infection is associated with CD8 T-cell responses to Gag-encoded antigens the core and carriage 'protective' human leukocyte antigen (HLA)-B alleles, but some controllers do not possess these attributes. As slower disease progression high levels antibodies Gag proteins, we have examined proteins in without HLA-B alleles.Plasma from 32 21 noncontrollers was for immunoglobulin G1 (IgG1) IgG2 virus lysates by western blot assay recombinant (r) p55 gp140 ELISA. killer (NK)...
The objective of this study is to determine the breadth HIV-1 Env-specific antibody-dependent cellular cytotoxicity (ADCC) in HIV controllers and progressors with a view design globally relevant vaccines.The ADCC towards four major Env subtypes was measured vitro for 11 progressors.Plasma from (including long-term slow progressors, viremic controllers, elite controller posttreatment controller) mostly infected subtype B, analysed responses. assays were performed against 10 gp120 8 gp140...
ABSTRACT The envelope protein of human immunodeficiency virus type 1 HIV-1 undergoes proteolytic cleavage in the Golgi complex to produce subunits designated gp120 and gp41, which remain noncovalently associated. While gp41 has a well-characterized oligomeric structure, maintenance gp41-independent intersubunit contacts remains contentious issue. Using recombinant vaccinia achieve high-level expression mammalian cells combined with gel filtration analysis, we were able isolate discrete form...
A functional disulfide bond in both the HIV envelope glycoprotein, gp120, and its immune cell receptor, CD4, is involved viral entry, compounds that block cleavage of these proteins inhibit entry infection. The bonds are cleaved at surface by small redox protein, thioredoxin. target gp120 mechanism were determined using a thioredoxin kinetic trapping mutant mass spectrometry. single was isolated but not gp160 precursor, extent reaction enhanced when bound to CD4. Cys(32) sulfur ion attacks...
BackgroundCombination antiretroviral therapy (cART) effectively controls human immunodeficiency virus (HIV) infection but does not eliminate HIV, and lifelong treatment is therefore required. HIV-specific cytotoxic T lymphocyte (CTL) responses decline following cART initiation. Alterations in other immune that may assist eliminating latent HIV infection, specifically antibody-dependent cellular cytotoxicity (ADCC) phagocytosis (ADP), are unclear.
The E2 glycoprotein of hepatitis C virus (HCV) is the major target broadly neutralizing antibodies (bNAbs) that are critical for efficacy a prophylactic HCV vaccine. We previously showed cell culture–derived, disulfide-linked high-molecular-weight (HMW) form receptor–binding domain lacking three variable regions, Δ123-HMW, elicits broad activity against seven genotypes HCV. A limitation to use this antigen it produced only at low yields and does not have homogeneous composition. Here, we...