A5059171093- HIV Research and Treatment
- HIV/AIDS drug development and treatment
- HIV/AIDS Research and Interventions
- BRCA gene mutations in cancer
- Genetic Associations and Epidemiology
- Genomic variations and chromosomal abnormalities
- Hepatitis B Virus Studies
- Hepatitis C virus research
- Immune Cell Function and Interaction
- Cystic Fibrosis Research Advances
- Sexual Differentiation and Disorders
- Medical and Biological Sciences
- History of Medical Practice
- Folate and B Vitamins Research
- Biochemical and Molecular Research
- Molecular Biology Techniques and Applications
- Nutrition, Genetics, and Disease
- Iron Metabolism and Disorders
23andMe (United States)
2019-2024
Johns Hopkins University
2013-2018
Johns Hopkins Medicine
2013-2018
Office of Infectious Diseases
2012
HIV-1 protease inhibitors (PIs) are among the most effective antiretroviral drugs. They characterized by highly cooperative dose-response curves that not explained current pharmacodynamic theory. An unresolved problem affecting clinical use of PIs is patients who fail PI-containing regimens often have virus lacks mutations, in apparent violation fundamental evolutionary Here, we show these issues can be through analysis effects on distinct steps viral life cycle. We found do affect virion...
In HIV-infected individuals receiving suppressive antiretroviral therapy, the virus persists indefinitely in a reservoir of latently infected cells. The proliferation these cells may contribute to stability and thus lifelong persistence HIV-1 individuals. Because replication process is highly error-prone, detection identical viral genomes distinct host provides evidence for clonal expansion We evaluated alignments unique, near-full-length sequences determine relationship between clonality...
Extraordinary viral sequence diversity and rapid genetic evolution are hallmarks of hepatitis C virus (HCV) infection. Viral has previously been shown to mediate escape from cytotoxic T-lymphocyte (CTL) neutralizing antibody responses in acute HCV continues during chronic infection, but the pressures driving these changes poorly defined. We analyzed plasma 5.2-kb hemigenomes multiple longitudinal time points isolated individuals Irish anti-D cohort, who were infected with a common source...
Catechol diether compounds have nanomolar antiviral and enzymatic activity against HIV with reverse transcriptase (RT) variants containing K101P, a mutation that confers high-level resistance to FDA-approved non-nucleoside inhibitors efavirenz rilpivirine. Kinetic data suggests RT (K101P) are as catalytically fit wild-type thus can potentially increase in the viral population more regimens include or Comparison of structures new crystal structure complex leading compound confirms K101P is...
Abstract Current guidelines recommend BRCA1 and BRCA2 genetic testing for individuals with a personal or family history of certain cancers. Three BRCA1/2 founder variants — 185delAG (c.68_69delAG), 5382insC (c.5266dupC), 6174delT (c.5946delT) are common in the Ashkenazi Jewish population. We characterized cohort more than 2,800 research participants 23andMe database who carry one three variants, evaluating two characteristics that typically used to BRCA testing: self-reported ancestry...
The second-generation HIV-1 integrase strand transfer inhibitor (InSTI) dolutegravir (DTG) has had a major impact on the treatment of infection. Here we describe important but previously undetermined pharmacodynamic parameters for DTG. We show that dose-response curve slope, which indicates cooperativity and is determinant antiviral activity, higher DTG than first-generation InSTIs. This steepness does not reflect inhibition multiple steps in life cycle, as case allosteric inhibitors...
Heterologous immunity is an important aspect of the adaptive immune response. We hypothesized that this process could modulate HIV-1-specific CD8+ T cell response, which has been shown to play role in HIV-1 and control. found stimulation peripheral blood mononuclear cells (PBMCs) from HIV-1-positive subjects with microbial peptides were cross-reactive immunodominant epitopes resulted dramatic expansion cells. Interestingly, TCR repertoire generated by ex vivo PBMCs using peptide was...
Carrier screening identifies reproductive risk for autosomal recessive and X-linked genetic conditions. Currently, some medical society guidelines continue to recommend ethnicity-based carrier conditions associated with Ashkenazi Jewish (AJ) ancestry. We assessed the utility limitations of these in a large, ethnically genetically diverse cohort genotyped individuals.
Despite antiretroviral therapy (ART), a latent reservoir of replication-competent HIV-1 persists in resting memory CD4 + T-cells and precludes cure 1-6 . Lorenzo-Redondo et al 7 analyzed sequences collected from three individuals during the first six months ART, discovered specific patterns sequence evolution, concluded that viral replication therapy. We believe these evolutionary are artifacts rapidly decaying subpopulations present not characteristic long-lived reservoir. The study...
Abstract Background: Three BRCA1 and BRCA2 founder variants (185delAG, 5382insC, 6174delT) are common in the Ashkenazi Jewish population. Our objective was to use data collected by direct-to-consumer (DTC) genetic testing (23andMe, Inc., Mountain View CA) determine frequency of these a generally unselected group genotyped individuals characterize cohort carrying one terms self-reported ancestry, personal family history cancer. Methods: Individuals were prior November 2017 on four custom...
ABSTRACT Current guidelines recommend BRCA1 and BRCA2 genetic testing for individuals with a personal or family history of certain cancers. Three BRCA1/2 founder variants — 185delAG (c.68_69delAG), 5382insC (c.5266dupC), 6174delT (c.5946delT) are common in the Ashkenazi Jewish population. We characterized cohort more than 2,800 research participants 23andMe database who carry one three variants, evaluating two characteristics that typically used to BRCA testing: self-reported ancestry...