A5091208578- HIV Research and Treatment
- HIV/AIDS drug development and treatment
- Immune Cell Function and Interaction
- HIV/AIDS Research and Interventions
- Cytomegalovirus and herpesvirus research
- T-cell and B-cell Immunology
- Monoclonal and Polyclonal Antibodies Research
- Neuroinflammation and Neurodegeneration Mechanisms
- Mosquito-borne diseases and control
- HIV-related health complications and treatments
- vaccines and immunoinformatics approaches
- Herpesvirus Infections and Treatments
- Virology and Viral Diseases
- Immunodeficiency and Autoimmune Disorders
- Immunotherapy and Immune Responses
- Glycosylation and Glycoproteins Research
- RNA Interference and Gene Delivery
- interferon and immune responses
- Blood groups and transfusion
- Viral Infections and Immunology Research
- Viral-associated cancers and disorders
- CAR-T cell therapy research
- Hepatitis C virus research
- Pneumocystis jirovecii pneumonia detection and treatment
- Viral Infections and Vectors
Peter Doherty Institute
2022-2024
The University of Melbourne
2009-2024
RMIT University
1999-2023
Monash University
2008-2022
MIT University
1999-2022
John Wiley & Sons (United States)
2022
Burnet Institute
2008-2017
Australian Regenerative Medicine Institute
2010-2014
University of Amsterdam
2012
Amsterdam UMC Location University of Amsterdam
2012
Abstract HIV-1 persists in peripheral blood monocytes individuals receiving highly active antiretroviral therapy (HAART) with viral suppression, despite these cells being poorly susceptible to infection vitro. Because very few harbor vivo, we considered whether a subset of might be more permissive infection. We show that minor CD16+ monocyte preferentially harbors infected on HAART when compared the majority (CD14highCD16−). confirmed this by vitro experiments showing were CCR5-using strains...
Abstract Astrocyte infection with human immunodeficiency virus (HIV) is considered rare, so astrocytes are thought to play a secondary role in HIV neuropathogenesis. By combining double immunohistochemistry, laser capture microdissection, and highly sensitive multiplexed polymerase chain reaction detect DNA single vivo, we showed that astrocyte extensive subjects HIV‐associated dementia, occurring up 19% of GFAP+ cells. In addition, frequency correlated the severity neuropathological changes...
ABSTRACT The viral determinants that underlie human immunodeficiency virus type 1 (HIV-1) neurotropism are unknown, due in part to limited studies on viruses isolated from brain. Previous suggest brain-derived macrophage tropic (M-tropic) and principally use CCR5 for entry. To better understand HIV-1 neurotropism, we primary autopsy brain, cerebral spinal fluid, blood, spleen, lymph node samples AIDS patients with dementia encephalitis. Isolates were characterized determine coreceptor usage...
ABSTRACT Most human immunodeficiency virus type 1 (HIV-1) viruses in the brain use CCR5 as principal coreceptor for entry into a cell. However, additional phenotypic characteristics are necessary HIV-1 neurotropism. Furthermore, neurotropic strains not necessarily neurovirulent. To better understand determinants of neurovirulence, we isolated from tissue samples three AIDS patients with dementia and encephalitis analyzed their ability to induce syncytia monocyte-derived macrophages (MDM)...
HIV infects tissue macrophages and brain microglia, which express lower levels of CD4 CCR5 than CD4+ T cells in peripheral blood. Mechanisms that enhance tropism for the CNS other tissues are not well understood. Here, we identify an envelope glycoprotein (Env) variant CD4-binding site gp120, Asn 283 (N283), is present at a high frequency from AIDS patients with HIV-associated dementia (HAD). N283 increases gp120 affinity by decreasing gp120-CD4 dissociation rate, enhancing capacity Envs to...
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...
Human immunodeficiency virus (HIV) persistence in blood and tissue reservoirs, including the brain, is a major barrier to HIV cure possible cause of comorbid disease. However, size replication competent nature central nervous system (CNS) reservoir unclear. Here, we used intact proviral DNA assay (IPDA) provide first quantitative assessment defective brain people with (PWH).Total, intact, proviruses were measured autopsy frontal lobe from viremic (n = 18) or virologically suppressed 12) PWH....
The genetic evolution of human immunodeficiency virus type 1 (HIV-1) in the brain is distinct from that lymphoid tissues, indicating tissue-specific compartmentalization virus. Few primary HIV-1 envelope glycoproteins (Envs) uncultured tissues have been biologically well characterized. In this study, we analyzed 37 full-length env genes biopsy and blood samples four patients with AIDS. Phylogenetic analysis intrapatient sequence sets showed clustering relative to sequences. However, no...
Background. Naive T cell recovery is critical for successful immune reconstitution after antiretroviral therapy (ART), but the relative contribution of CD31+ and CD31- naive cells to viral persistence unknown.
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...
Elite non-progressors (plasma viral load <50 copies/ml while antiretroviral naive) constitute a tiny fraction of HIV-infected individuals. After 12 years follow-up cohort 13 long-term (LTNP) identified from 135 individuals with transfusion-acquired HIV infection, 5 remained LTNP after 23 to 26 but only 3 retained elite status. We examined the mechanisms that differentiated delayed progressors in this cohort. A survival advantage was conferred on subjects, who had at least one host genetic...
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...
Astrocytes are extensively infected with HIV-1 in vivo and play a significant role the development of HIV-1-associated neurocognitive disorders. Despite their extensive infection, little is known about how astrocytes become infected, since they lack cell surface CD4 expression. In present study, we investigated fate upon infection astrocytes. were found to bind harbor virus followed by biphasic decay, detectable out 72 hours. was observed associate CD81-lined vesicle structures. shRNA...
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...