A5072751680- HIV Research and Treatment
- HIV/AIDS drug development and treatment
- Immune Cell Function and Interaction
- HIV/AIDS Research and Interventions
- Monoclonal and Polyclonal Antibodies Research
- vaccines and immunoinformatics approaches
- Glycosylation and Glycoproteins Research
- Immunodeficiency and Autoimmune Disorders
- Mosquito-borne diseases and control
- interferon and immune responses
- HIV-related health complications and treatments
- Viral Infections and Immunology Research
- Virology and Viral Diseases
- Immunotherapy and Immune Responses
- Diabetes Management and Education
- Neuroinflammation and Neurodegeneration Mechanisms
- Herpesvirus Infections and Treatments
- Microbial Community Ecology and Physiology
- HIV, TB, and STIs Epidemiology
- Animal Disease Management and Epidemiology
Burnet Institute
2007-2017
Peter Doherty Institute
2017
The University of Melbourne
2016-2017
The Royal Melbourne Hospital
2017
Monash University
2004-2015
Australian Regenerative Medicine Institute
2015
Background Topical microbicides, used by women to prevent the transmission of HIV and other sexually transmitted infections are urgently required. Dendrimers highly branched nanoparticles being developed as microbicides. However, anti-HIV HSV structure-activity relationship dendrimers comprising benzyhydryl amide cores lysine branches, a comprehensive analysis their broad-spectrum activity mechanism action have not been published. Methods Findings with optimized against HIV-1 HSV-2 were...
ABSTRACT Maraviroc (MVC) inhibits the entry of human immunodeficiency virus type 1 (HIV-1) by binding to and modifying conformation CCR5 extracellular loops (ECLs). Resistance MVC results from alterations in HIV-1 gp120 envelope glycoproteins (Env) enabling recognition drug-bound CCR5. To better understand mechanisms underlying resistance, we characterized virus-cell interactions vitro -generated MVC-resistant (MVC-Res Env), comparing them with those sensitive parental (MVC-Sens Env). In...
Abstract Background CCR5-restricted (R5) human immunodeficiency virus type 1 (HIV-1) variants cause CD4+ T-cell loss in the majority of individuals who progress to AIDS, but mechanisms underlying pathogenicity R5 strains are poorly understood. To better understand envelope glycoprotein (Env) determinants contributing viruses, we characterized 37 full-length Envs from cross-sectional and longitudinal viruses isolated blood patients with asymptomatic infection or referred as pre-AIDS (PA) AIDS...
Abstract Background The CCR5 antagonist maraviroc (MVC) inhibits human immunodeficiency virus type 1 (HIV-1) entry by altering the extracellular loops (ECL), such that gp120 envelope glycoproteins (Env) no longer recognize CCR5. mechanisms of HIV-1 resistance to MVC, only licensed for clinical use are poorly understood, with insights into MVC almost exclusively limited knowledge obtained from in vitro studies or other antagonists. To more precisely understand vivo , we characterized Envs...
Abstract We molecularly characterized human immunodeficiency virus type 1 (HIV‐1) present in pure populations of astrocytes, macrophages, and multinucleated giant cells isolated using laser capture microdissection from brain tissue two patients who died with HIV‐associated dementia. The V3 region the HIV‐1 envelope ( env ) gene was amplified pure‐cell populations, multiple clones were sequenced. In both patients, sequences distinct astrocytes compared neighboring macrophages or...
ABSTRACT Most human immunodeficiency virus type 1 (HIV-1) strains isolated from the brain use CCR5 for entry into macrophages and microglia. Strains that both CXCR4 (R5X4 strains) have been identified in brains of some individuals, but mechanisms underlying persistence R5X4 viruses compartmentalized between other tissue reservoirs are unknown. Here, we characterized changes HIV-1 envelope (Env) enhance tropism variants or lymphoid tissue. Envs derived two individuals had enhanced usage...
HIV-1 subtype C (C-HIV) is responsible for most cases worldwide. Although the pathogenesis of C-HIV thought to predominantly involve CCR5-restricted (R5) strains, we do not have a firm understanding how frequently CXCR4-using (X4 and R5X4) variants emerge in subjects with progressive infection. Nor completely understand molecular determinants coreceptor switching by variants. Here, characterized panel envelope glycoproteins (Envs) (n = 300) cloned sequentially from plasma 21 antiretroviral...
Over the past decade antiretroviral drugs have dramatically improved prognosis for HIV-1 infected individuals, yet achieving better access to vulnerable populations remains a challenge. The principal obstacle CCR5-antagonist, maraviroc, from being more widely used in anti-HIV-1 therapy regimens is that pre-treatment genotypic "tropism tests" determine virus susceptibility maraviroc been developed primarily subtype B strains, which account only 10% of infections worldwide. We therefore...
We characterized human immunodeficiency virus type 1 (HIV-1) envelope glycoproteins (Env) isolated from two HIV-1-infected CCR5delta32 homozygotes. Envs both subjects used CCR5 and CXCR4 for entry into transfected cells. Most R5X4 were lymphocyte-tropic exclusively peripheral blood mononuclear cells (PBMC), but a subset was dually lymphocyte- macrophage-tropic either or PBMC monocyte-derived macrophages. The persistence of CCR5-using HIV-1 in homozygotes suggests the conserved binding domain...
Abstract Along with an enhanced interaction CD4, highly M-tropic HIV-1 Envs have altered mechanism of engagement CCR5. BR-derived strains exceptional ability to enter macrophages via mechanisms involving their gp120 Env that remain incompletely understood. Here, we used cell-based affinity-profiling methods and mathematical modeling generate quantitative VERSA metrics simultaneously measure Env-CD4 Env-CCR5 interactions. These were analyzed distinguish the phenotypes non-M-tropic CCR5-using...
Macrophage tropism of human immunodeficiency virus type 1 (HIV-1) is distinct from coreceptor specificity the viral envelope glycoproteins (Env), but virus-cell interactions that contribute to efficient HIV-1 entry into macrophages, particularly via CXCR4, are not well understood. Here, we characterized a panel Envs use CCR5 (n = 14) or CXCR4 6) enter monocyte-derived macrophages (MDM) with various degrees efficiency. Our results show CCR5-mediated MDM by Env-pseudotyped reporter viruses...
Abstract Background The majority of HIV-1 subjects worldwide are infected with subtype C (C-HIV). Although C-HIV predominates in developing regions the world such as Southern Africa and Central Asia, is also spreading rapidly countries more developed economies health care systems, whose populations likely to have access wider treatment options, including CCR5 antagonist maraviroc (MVC). ability reliably determine coreceptor usage therefore becoming increasingly important. In silico V3...
Background Induction of broadly neutralizing antibodies, such as the monoclonal antibodies IgGb12, 2F5 and 2G12, is objective most antibody-based HIV-1 vaccine undertakings. However, despite relative conserved nature epitopes targeted by these mechanisms underlying sensitivity circulating variants to are not fully understood. Here we have studied that emerge during disease progression in relation molecular alterations viral envelope glycoproteins (Env), using a panel primary R5 isolates...
Tyrosine (Tyr) sulfation is a common post-translational modification that implicated in variety of important biological processes, including the fusion and entry human immunodeficiency virus type-1 (HIV-1). A number sulfated Tyr (sTyr) residues on N-terminus CCR5 chemokine receptor are involved crucial binding interaction with gp120 HIV-1 envelope glycoprotein. Despite established importance these sTyr residues, exact structural functional role this infection not fully understood. Detailed...
The efficiency of CD4/CCR5 mediated HIV-1 entry has important implications for pathogenesis and transmission. receptor affinity profiling (Affinofile) system analyzes quantifies the infectivity envelopes (Envs) across a spectrum expression levels distills these data into set Affinofile metrics. shed light on how differential usage efficiencies contributes to an array Env phenotypes associated with cellular tropism, viral pathogenesis, CCR5 inhibitor resistance. To facilitate more rapid,...
Abstract Background At early stages of infection CCR5 is the predominant HIV-1 coreceptor, but in approximately 50% those infected CXCR4-using viruses emerge with disease progression. This coreceptor switch correlated an accelerated However, that maintain virus exclusively restricted to (R5) also develop AIDS. We have previously reported R5 variants these "non-switch virus" patients evolve during progression towards a more replicative phenotype exhibiting altered interactions. DC-SIGN C-type...
Human immunodeficiency virus type 1 (HIV-1) subtype C (C-HIV) is spreading rapidly and now responsible for >50% of HIV-1 infections worldwide, >95% in southern Africa central Asia. These regions are burdened with the overwhelming majority infections, yet we know very little about pathogenesis C-HIV. In addition to CCR5 CXCR4, envelope glycoproteins (Env) may engage a variety alternative coreceptors entry into transfected cells. Whilst do not appear have broad role mediating primary cells,...
We studied the evolution and compartmentalization of nef/long terminal repeat (nef/LTR)-deleted human immunodeficiency virus type 1 (HIV-1) from a long-term survivor who developed HIV-associated dementia (HIVD). Analysis sequential blood-derived HIV-1 isolated before during HIVD revealed persistent R5X4 phenotype progressive loss nef/LTR sequence; in contrast, present cerebrospinal fluid had an R5 phenotype, distinct sequence unique deletions additional nuclear factor- kappa B sites...
The leading causes of morbidity and mortality for people in high-income countries living with HIV are now non-AIDS malignancies, cardiovascular disease other non-communicable diseases associated ageing. This protocol describes the trial HealthMap, a model care (PWHIV) that includes use an interactive shared health record self-management support. aims HealthMap to evaluate engagement PWHIV healthcare providers model, its effectiveness reducing coronary heart risk, enhancing self-management,...