A5076145110- HIV Research and Treatment
- SARS-CoV-2 and COVID-19 Research
- Genomics and Phylogenetic Studies
- vaccines and immunoinformatics approaches
- Animal Virus Infections Studies
- Plant Virus Research Studies
- Virology and Viral Diseases
- SARS-CoV-2 detection and testing
- HIV/AIDS drug development and treatment
- T-cell and B-cell Immunology
- Viral Infections and Vectors
- Bacteriophages and microbial interactions
- Cervical Cancer and HPV Research
- COVID-19 epidemiological studies
- interferon and immune responses
- Viral Infections and Outbreaks Research
- COVID-19 diagnosis using AI
- Microbial Community Ecology and Physiology
- Microbial infections and disease research
- Insect symbiosis and bacterial influences
- COVID-19 Clinical Research Studies
- RNA and protein synthesis mechanisms
- Hepatitis C virus research
- Immune Response and Inflammation
- Bat Biology and Ecology Studies
Fred Hutch Cancer Center
2023-2025
University of Arizona
2018-2023
Howard Hughes Medical Institute
2023
University of Washington
2012-2016
Seattle University
2012
A not-so-random integration for HIV Even in the face of a cocktail antiretroviral drugs, manages to hang on. It does so by integrating its own genome into those host cells, where it persists latent state. To better understand this process, Wagner et al. determined sites integrated three HIV-infected patients treated with drugs more than decade. They found an over-representation genes associated cancer and cell proliferation. Also, multiple cells same individual harbored sites. This suggests...
Accurate understanding of the global spread emerging viruses is critical for public health responses and anticipating preventing future outbreaks. Here we elucidate when, where, how earliest sustained severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission networks became established in Europe North America. Our results suggest that rapid early interventions successfully prevented introductions virus from taking hold Germany United States. Other, later China to both Italy...
Summary As of January 2021, the highly transmissible B.1.1.7 variant SARS-CoV-2, which was first identified in United Kingdom (U.K.), has gained a strong foothold across world. Because sudden and rapid rise B.1.1.7, we investigated prevalence growth dynamics this States (U.S.), tracking it back to its early emergence onward local transmission. We found that RT-qPCR testing anomaly S gene target failure (SGTF), observed U.K., reliable proxy for detection. sequenced 212 SARS-CoV-2 genomes...
Abstract Accurate understanding of the global spread emerging viruses is critically important for public health response and anticipating preventing future outbreaks. Here, we elucidate when, where how earliest sustained SARS-CoV-2 transmission networks became established in Europe United States (US). Our results refute prior findings erroneously linking cases January 2020 with outbreaks that occurred weeks later. Instead, rapid interventions successfully prevented onward those early Germany...
ABSTRACT The RV144 HIV-1 vaccine trial demonstrated partial efficacy of 31% against infection. Studies into possible correlates protection found that antibodies specific to the V1 and V2 (V1/V2) region envelope correlated inversely with infection risk viruses isolated from participants contained genetic signatures vaccine-induced pressure in V1/V2 region. We explored hypothesis could be partly attributed selection by vaccine-primed T cells. performed a T-cell-based sieve analysis...
The RV144 clinical trial showed the partial efficacy of a vaccine regimen with an estimated (VE) 31% for protecting low-risk Thai volunteers against acquisition HIV-1. impact vaccine-induced immune responses can be investigated through sieve analysis HIV-1 breakthrough infections (infected and placebo recipients). A V1/V2-targeted comparison genomes viruses identified two V2 amino acid sites that differed between groups. Here we extended V1/V2 to entire genome using array methods based on...
To overcome the problem of HIV-1 variability, candidate vaccine antigens have been designed to be composed conserved elements proteome. Such vaccines could improved with a better understanding both evolutionary constraints and fitness cost specific mutations. We evaluated in vitro 23 mutations engineered subtype B Gag-p24 Center-of-Tree (COT) protein through competition assays. While some at sites exacted high cost, as expected under assumption that most residue confers highest fitness,...
With very little direct biological data of HIV-1 from before the 1980s, far-reaching evolutionary and epidemiological inferences regarding long prediscovery phase this pandemic are based on extrapolations by phylodynamic models genomic sequences gathered mostly over recent decades. Here, using a sensitive multiplex RT-PCR assay, we screened 1,645 formalin-fixed paraffin-embedded tissue specimens collected for pathology diagnostics in Central Africa between 1958 1966. We report near-complete...
In December of 2019, a novel coronavirus, SARS-CoV-2, emerged in the city Wuhan, China, causing severe morbidity and mortality. Since then, virus has swept across globe, millions confirmed infections hundreds thousands deaths. To better understand nature pandemic introduction spread Arizona, we sequenced viral genomes from clinical samples tested at TGen North Clinical Laboratory, Arizona Department Health Services, those collected as part community surveillance projects State University...
Paramyxoviruses are a diverse group of negative-sense, single-stranded RNA viruses which several species cause significant mortality and morbidity. In recent years the collection paramyxovirus sequences detected in wild mammals has substantially grown; however, little is known about diversity North American mammals. To better understand natural diversity, host range, specificity, we sought to comprehensively characterize paramyxoviruses across range cooccurring small southern Arizona. We...
Nipah virus recurrently spills over to humans, causing fatal infections. The viral receptor-binding protein (RBP or G) attaches host receptors and is a major target of neutralizing antibodies. Here we use deep mutational scanning measure how all amino-acid mutations the RBP affect cell entry, receptor binding, escape from We identify functionally constrained regions RBP, including sites involved in oligomerization, along with that differentially modulate binding its two ephrin receptors. map...
To understand the interplay between host cytotoxic T-lymphocyte (CTL) responses and mechanisms by which HIV-1 evades them, we studied viral evolutionary patterns associated with CTL in six linked transmission pairs. sequences corresponding to full-length p17 p24 gag were generated 454 pyrosequencing for all pairs near time of transmission, seroconverting partners followed a median 847 days postinfection. T-cell screened gamma interferon/interleukin-2 (IFN-γ/IL-2) FluoroSpot using autologous...
Upon infection, DNA viruses can be sensed by pattern recognition receptors (PRRs), leading to the activation of type I and III interferons block infection. Therefore, must inhibit these signaling pathways, avoid being detected, or both. Papillomavirus virions are trafficked from early endosomes Golgi apparatus wait for onset mitosis complete nuclear entry. This unique subcellular trafficking strategy avoids detection cytoplasmic PRRs, a property that may contribute establishment However, as...
Massively parallel sequencing (MPS) technologies, such as 454-pyrosequencing, allow for the identification of variants in sequence populations at lower levels than consensus and most single-template Sanger experiments. We sought to determine if greater depth population sampling attainable using MPS technology would detection minor HIV founder virus very early infection instances where detects only a single variant. compared nucleotide polymorphisms (SNPs) during acute HIV-1 from 32 subjects...
<ns3:p>The COVID-19 pandemic has led to a rapid accumulation of SARS-CoV-2 genomes, enabling genomic epidemiology on local and global scales. Collections genomes from resources such as GISAID must be subsampled enable computationally feasible phylogenetic other analyses. We present genome-sampler, software package that supports sampling collections viral across multiple axes including time genome isolation, location diversity. The is modular in design so these or future approaches can...
ABSTRACT Recall T cell responses to HIV-1 antigens are used as a surrogate for endogenous cellular immune generated during infection. Current methods of identifying antigen-specific reactivity in infection use bulk peripheral blood mononuclear cells (PBMC) yet ignore professional antigen-presenting (APC) that could reveal otherwise hidden responses. In the present study, peptides representing autologous variants major histocompatibility complex (MHC) class I-restricted epitopes from Gag and...
<ns3:p>The COVID-19 pandemic has led to a rapid accumulation of SARS-CoV-2 genomes, enabling genomic epidemiology on local and global scales. Collections genomes from resources such as GISAID must be subsampled enable computationally feasible phylogenetic other analyses. We present genome-sampler, software package that supports sampling collections viral across multiple axes including time genome isolation, location diversity. The is modular in design so these or future approaches can...
Abstract Motivation: Pyrosequencing technology provides an important new approach to more extensively characterize diverse sequence populations and detect low frequency variants. However, the promise of this has been difficult realize, as careful correction sequencing errors is crucial distinguish rare variants (∼1%) in infected host with high sensitivity specificity. Results: We developed a approach, referred Indel Carryforward Correction (ICC), cluster sequences without substitutions...