A5056145693- HIV Research and Treatment
- HIV/AIDS Research and Interventions
- HIV/AIDS drug development and treatment
- Immune Cell Function and Interaction
- Cytomegalovirus and herpesvirus research
- Parasites and Host Interactions
- Evolution and Genetic Dynamics
- HIV-related health complications and treatments
- T-cell and B-cell Immunology
- Mosquito-borne diseases and control
- vaccines and immunoinformatics approaches
- Monoclonal and Polyclonal Antibodies Research
- Hepatitis C virus research
- Hepatitis B Virus Studies
- Immunotherapy and Immune Responses
- Neuroinflammation and Neurodegeneration Mechanisms
- Reproductive tract infections research
- Bacteriophages and microbial interactions
- Research on Leishmaniasis Studies
- CRISPR and Genetic Engineering
- SARS-CoV-2 and COVID-19 Research
- Malaria Research and Control
- Herpesvirus Infections and Treatments
- SARS-CoV-2 detection and testing
- Cardiac, Anesthesia and Surgical Outcomes
Communities In Schools of Orange County
2025
University of North Carolina at Chapel Hill
2014-2024
UNC Lineberger Comprehensive Cancer Center
2014-2024
MRC Clinical Trials Unit at UCL
2009-2023
University College London
2014-2023
Imperial College London
2019-2023
CURE International UK
2020-2023
Segeberger Kliniken
2023
AIDS United
2023
Johns Hopkins University Center for AIDS Research
2014-2023
Human immunodeficiency virus type 1 (HIV-1) infection of the central nervous system (CNS) can lead to development HIV-1-associated dementia (HAD). We examined virological characteristics HIV-1 in cerebrospinal fluid (CSF) HAD subjects explore association between independent viral replication CNS and overt dementia. found that genetically compartmentalized CCR5-tropic (R5) T cell-tropic macrophage-tropic populations were independently detected CSF diagnosed with Macrophage-tropic diverse,...
Although antiretroviral therapy (ART) is highly effective at suppressing HIV-1 replication, the virus persists as a latent reservoir in resting CD4+ T cells during therapy. This forms even when ART initiated early after infection, but dynamics of its formation are largely unknown. The viral reservoirs individuals who initiate chronic infection generally larger and genetically more diverse than those acute consistent with hypothesis that formed continuously throughout untreated infection. To...
After initiating antiretroviral therapy (ART), a rapid decline in HIV viral load is followed by long period of undetectable viremia. Viral outgrowth assay suggests the reservoir continues to slowly. Here, we use full-length sequencing longitudinally study proviral landscape four subjects on ART investigate selective pressures influencing dynamics treatment-resistant reservoir. We find intact and defective proviruses that contain genetic elements favoring efficient protein expression decrease...
Brain microglia (MG) may serve as a human immunodeficiency virus 1 (HIV) reservoir and ignite rebound viremia following cessation of antiretroviral therapy (ART), but they have yet to be proven harbor replication-competent HIV. Here, we isolated brain myeloid cells (BrMCs) from nonhuman primates rapid autopsy people with HIV (PWH) on ART sought evidence persistent viral infection. BrMCs predominantly displayed microglial markers, in which up 99.9% the were TMEM119+ MG. Total integrated SIV...
Abstract We performed a 1012-generation mutation-accumulation (MA) experiment in the yeast, Saccharomyces cerevisiae. The MA lines exhibited significant reduction mean fitness and increase variance fitness. found that 5.75% of fitness-altering mutations accumulated were beneficial. This finding contradicts widely held belief nearly all are deleterious. mutation rate was estimated as 6.3 × 10−5 per haploid genome generation average heterozygous effect 0.061. These estimates compatible with...
Compartmentalized HIV-1 replication within the central nervous system (CNS) likely provides a foundation for neurocognitive impairment and potentially important tissue reservoir. The timing of emergence character this local CNS has not been defined in population subjects. We examined frequency elevated cerebrospinal fluid (CSF) RNA concentration, nature CSF viral populations compared to blood, presence cellular inflammatory response (with potential bring infected cells into CNS) using paired...
In African children, distinguishing severe falciparum malaria from other febrile illnesses with coincidental Plasmodium parasitaemia is a major challenge. P. histidine-rich protein 2 (PfHRP2) released by mature sequestered parasites and can be used to estimate the total parasite burden. We investigated prognostic significance of plasma PfHRP2 it malaria-attributable fraction in children diagnosed malaria.Admission was measured prospectively (from Mozambique, The Gambia, Kenya, Tanzania,...
Understanding human immunodeficiency virus type 1 (HIV-1) transmission is central to developing effective prevention strategies, including a vaccine. We compared phenotypic and genetic variation in HIV-1 env genes from subjects acute/early infection with chronic infections the context of subtype C heterosexual transmission. found that transmitted viruses all used CCR5 required high levels CD4 infect target cells, suggesting selection for replication T cells not macrophages after In addition,...
Defining a macrophage-tropic phenotype for HIV-1 to assess role in pathogenesis is complicated by the fact that isolates vary continuously their ability enter monocyte-derived macrophages (MDMs) vitro, and MDMs support entry. To overcome these limitations, we identified consistent differences entry phenotypes between five paired blood-derived, T cell-tropic env genes, four of which are CCR5-using (R5) one CXCR4-using (X4), cerebrospinal fluid (CSF)-derived, R5 genes. We performed assays...
The mechanisms by which human immunodeficiency virus type 1 (HIV-1) crosses mucosal surfaces to establish infection are unknown. Acidic genital secretions of HIV-1-infected women contain HIV-1 likely coated antibody. We found that the combination acidic pH and Env-specific IgG, including from cervicovaginal seminal fluids individuals, augmented transcytosis across epithelial cells as much 20-fold compared with IgG at neutral or non-specific either pH. Enhanced was observed clinical isolates,...
Background. In malaria-endemic settings, asymptomatic parasitemia complicates the diagnosis of malaria. Histidine-rich protein 2 (HRP2) is produced by Plasmodium falciparum, and its plasma concentration reflects total body parasite burden. We aimed to define malaria-attributable fraction severe febrile illness, using distributions P. falciparum HRP2 (PfHRP2) concentrations from parasitemic children with different clinical presentations.
Abstract Background Human immunodeficiency virus type 1 (HIV-1) populations are detected in cerebrospinal fluid (CSF) of some people on suppressive antiretroviral therapy (ART). Detailed analysis these may reveal whether they produced by central nervous system (CNS) reservoirs. Methods We performed a study 101 asymptomatic participants stable ART. HIV-1 RNA concentrations were cross-sectionally measured CSF and plasma. In with sufficient for analysis, viral genetically phenotypically...
HIV-1 is typically CCR5 using (R5) and T cell tropic (T-tropic), targeting memory CD4(+) cells throughout acute chronic infections. However, viruses can expand into alternative types. Macrophage-tropic (M-tropic) variants have evolved to infect macrophages, which only low levels of surface CD4. Most M-tropic been isolated from the central nervous system during late-stage infection. We used env genes well-defined, subject-matched T-tropic characterize phenotypic features Env protein. found...
Background The risk of severe COVID-19 disease is known to be higher in older individuals and those with underlying health conditions. Understanding the number at increased illness, how this varies between countries may inform design possible strategies shield highest risk. Methods We estimated by age (5-year groups), sex country (n=188) based on prevalence data from Global Burden Disease (GBD) study for 2017 United Nations population estimates 2020. also calculated without an condition that...
Cannibalism, a widespread phenomenon in nature, can both reduce competitors and introduce high-quality food into the cannibal's diet. We investigated dietary benefits of cannibalism for larvae multicolored Asian lady beetle, Harmonia axyridis (Pallas). Cannibalism might benefit by allowing cannibals to take advantage prey-detoxification already completed victim or different, perhaps more diverse, feeding history victim. In two laboratory experiments we reared H. with aphid prey, without...
Abstract Background In malaria endemic areas, individuals are frequently asymptomatic and may be undetected by conventional microscopy or newer, rapid diagnostic tests. Molecular techniques allow a more accurate assessment of this parasite burden, the extent which is important for control. This study examines relative prevalence sub-microscopic level carriage clonal complexity infections (multiplicity infection) over range endemicities in region north-eastern Tanzania where altitude an...
HIV-1 subtype B replication in the CNS can occur CD4+ T cells or macrophages/microglia adults. However, little is known about infection children ability of C to evolve macrophage-tropic variants. In this study, we examined variants ART-naïve aged three years younger determine viral genotypes and phenotypes associated with pediatric infection. We populations blood CSF 43 Malawian neurodevelopmental delay acute neurological symptoms. Using single genome amplification (SGA) phylogenetic...