Barbara L. Shacklett

ORCID: 0000-0002-7067-732X
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About
Contact & Profiles
Research Areas
  • HIV Research and Treatment
  • Immune Cell Function and Interaction
  • HIV/AIDS Research and Interventions
  • T-cell and B-cell Immunology
  • Cytomegalovirus and herpesvirus research
  • Reproductive System and Pregnancy
  • Adolescent Sexual and Reproductive Health
  • Herpesvirus Infections and Treatments
  • Reproductive tract infections research
  • HIV-related health complications and treatments
  • HIV/AIDS drug development and treatment
  • HIV, Drug Use, Sexual Risk
  • Immunotherapy and Immune Responses
  • Sex work and related issues
  • Cervical Cancer and HPV Research
  • Virus-based gene therapy research
  • Reproductive Health and Contraception
  • Neuroinflammation and Neurodegeneration Mechanisms
  • Immune Response and Inflammation
  • COVID-19 Clinical Research Studies
  • Bacteriophages and microbial interactions
  • Pneumocystis jirovecii pneumonia detection and treatment
  • Long-Term Effects of COVID-19
  • Anthropological Studies and Insights
  • Parvovirus B19 Infection Studies

University of California, Davis
2015-2025

University of California Davis Medical Center
1994-2023

California State University, Sacramento
2023

University of Washington
2018

GTx (United States)
2018

Zero to Three
2017

University of California System
2016

Bipar
1994-2012

Office of Infectious Diseases
2007

Gladstone Institutes
2002-2005

A low CD4/CD8 ratio in elderly HIV-uninfected adults is associated with increased morbidity and mortality. subset of HIV-infected receiving effective antiretroviral therapy (ART) fails to normalize this ratio, even after they achieve normal CD4+ T cell counts. The immunologic clinical characteristics phenotype remain undefined. Using data from four distinct cohorts three trials, we show that a during otherwise ART (after CD4 count recovery above 500 cells/mm3) number immunological...

10.1371/journal.ppat.1004078 article EN cc-by PLoS Pathogens 2014-05-15

Although the gut-associated lymphoid tissue (GALT) is an important early site for human immunodeficiency virus (HIV) replication and severe CD4+ T-cell depletion, our understanding limited about restoration of gut mucosal immune system during highly active antiretroviral therapy (HAART). We evaluated kinetics viral suppression, restoration, gene expression, HIV-specific CD8+ responses in longitudinal gastrointestinal biopsy peripheral blood samples from patients initiating HAART primary HIV...

10.1128/jvi.00120-06 article EN Journal of Virology 2006-07-27

A rare subset of human immunodeficiency virus (HIV)-infected individuals maintains undetectable HIV RNA levels without therapy ("elite controllers"). To clarify the role T-cell responses in mediating control, we compared HLA class I polymorphisms and HIV-specific among a large cohort elite controllers (HIV-RNA < 75 copies/ml), "viremic" (low-level viremia therapy), "noncontrollers" (high-level viremia), "antiretroviral suppressed" (undetectable HIV-RNA on antiretroviral therapy). The...

10.1128/jvi.02176-07 article EN Journal of Virology 2008-03-20

Some human immunodeficiency virus (HIV)-infected individuals are not able to achieve a normal CD4(+) T cell count despite prolonged, treatment-mediated viral suppression. We conducted an intensification study assess whether residual replication contributes replenishment of the latent reservoir and mucosal HIV-specific responses limit size.Thirty treated subjects with counts <350 cells/mm(3) suppression for ≥ 1 year were randomized add raltegravir (400 mg twice daily) or matching placebo 24...

10.1093/infdis/jiq138 article EN The Journal of Infectious Diseases 2011-03-14

ABSTRACT Highly active antiretroviral therapy (HAART) enables long-term suppression of plasma HIV-1 loads in infected persons, but low-level virus persists and rebounds following cessation therapy. During HAART, this resides latently cells, such as resting CD4 + T other cell types that may support residual replication. Therapeutic eradication will require elimination from all reservoirs. We report here a comprehensive analysis these reservoirs fluids, tissues rhesus macaque model mimics...

10.1128/jvi.02356-09 article EN Journal of Virology 2009-12-24

Objectives: The objective of this article is to investigate the contribution colon and blood CD4+ T-cell subsets expressing chemokine receptor CCR6 HIV persistence during antiretroviral therapy. Design: Matched sigmoid biopsies samples (n = 13) as well leukapheresis 20) were collected from chronically HIV-infected individuals receiving Subsets T cells with distinct differentiation/polarization profiles identified using surface markers follows: memory (TM, CD45RA−), central (TCM;...

10.1097/qad.0000000000001309 article EN AIDS 2016-11-09

The character of central nervous system (CNS) HIV infection and its effects on neuronal integrity vary with evolving systemic infection. Using a cross-sectional design archived samples, we compared concentrations cerebrospinal fluid (CSF) biomarkers in 143 samples from 8 HIV-infected subject groups representing spectrum untreated progression viral suppression: primary infection; four chronic neuroasymptomatic (NA) subjects defined by blood CD4+ T cells >350, 200–349, 50–199, <50 cells/µL;...

10.1371/journal.pone.0116081 article EN cc-by PLoS ONE 2014-12-26

Toll-like receptor 7 (TLR7) agonists, in combination with other therapies, can induce sustained control of simian-human immunodeficiency virus (SHIV) or simian (SIV) nonhuman primates. Here, we report the results a randomized, double-blind, placebo-controlled phase 1b clinical trial an oral TLR7 agonist, vesatolimod, HIV-1-infected controllers on antiretroviral therapy (ART). We randomized participants 2:1 to receive vesatolimod (n = 17) placebo 8) once every week for total 10 doses while...

10.1126/scitranslmed.abg3071 article EN Science Translational Medicine 2021-06-23

The cytoplasmic domains of the transmembrane (TM) envelope proteins (TM-CDs) most retroviruses have a Tyr-based motif, YXXO, in their membrane-proximal regions. This signal is involved trafficking and endocytosis membrane receptors via clathrin-associated AP-1 AP-2 adaptor complexes. We used CD8-TM-CD chimeras to investigate role motif human immunodeficiency virus type 1 (HIV-1), simian (SIV), T-leukemia (HTLV-1) TM-CDs cell surface expression glycoprotein. Flow cytometry confocal microscopy...

10.1128/jvi.73.2.1350-1361.1999 article EN Journal of Virology 1999-02-01

The efficacy of antiretroviral postexposure prophylaxis (PEP) against infection with human immunodeficiency virus (HIV) following occupational exposures has prompted the use PEP after nonoccupational exposures. There are, however, important differences between and exposures, effectiveness exposure is unknown. We sought to describe occurrence circumstances HIV seroconversion PEP.HIV uninfected individuals reporting potential sexual or injection drug in preceding 72 h received a 28-day regimen...

10.1086/497268 article EN Clinical Infectious Diseases 2005-10-19

A small percentage of human immunodeficiency virus (HIV)-infected individuals, termed elite controllers, are able to spontaneously control HIV replication in blood. As the gastrointestinal mucosa is an important site transmission and as well CD4+ T-cell depletion, it understand nature immune responses occurring this compartment. Although role HIV-specific CD8+ mucosal tissues has been described, few studies have investigated T cells. In study, we assessed rectal 28 "controllers" (viral load...

10.1128/jvi.00980-10 article EN Journal of Virology 2010-08-19

ABSTRACT Gut-associated lymphoid tissue (GALT) is a major site of HIV replication and CD4 + T cell depletion. Furthermore, microbial translocation facilitated by mucosal damage likely contributes to the generalized immune activation observed in infection. Regulatory cells (Treg) help maintain homeostasis suppress harmful during infection; however, case persistent viral infections such as HIV, their role less clear. Although number studies have examined Treg blood chronic infection, few...

10.1128/jvi.05608-11 article EN Journal of Virology 2011-09-01

The study of HIV-infected "controllers" who are able to maintain low levels plasma HIV RNA in the absence antiretroviral therapy (ART) may provide insights for cure and vaccine strategies. Despite maintaining very viremia, controllers have elevated immune activation accelerated atherosclerosis. However, degree which low-level replication contributes these phenomena is not known. Sixteen asymptomatic were prospectively treated with ART 24 weeks. Controllers had a statistically significant...

10.1371/journal.ppat.1003691 article EN cc-by PLoS Pathogens 2013-10-10

Objective To characterize the evolution of central nervous system (CNS) inflammation in HIV-1 infection applying a panel cerebrospinal fluid (CSF) inflammatory biomarkers to grouped subjects representing broad spectrum systemic immune suppression, CNS injury and viral control. Methods This is cross-sectional analysis archived CSF blood samples, assessing concentrations 10 functionally diverse soluble by immunoassays 143 HIV-1-infected divided into 8 groups: untreated primary (PHI); four...

10.1371/journal.pone.0250987 article EN cc-by PLoS ONE 2021-05-13

With most of the T cells residing in tissue, not blood, developing noninvasive methods for vivo quantification their biodistribution and kinetics is important studying role immune response memory. This study presents first use dynamic positron emission tomography (PET) kinetic modeling measurement CD8

10.1126/sciadv.adh7968 article EN cc-by-nc Science Advances 2023-10-12

Spliced messages encoded by two distinct strains of feline immunodeficiency virus (FIV) were identified. Two the cDNA clones represented mRNAs with bicistronic capacity. The first coding exon contained a short open reading frame (orf) unknown function, designated orf 2. After translational stop, this L region env orf. resides 5' to predicted leader sequence env. second H orf, which began 3' and extended into U3 long terminal repeat. in-frame splicing orfs created FIV rev gene. Site-directed...

10.1128/jvi.66.9.5464-5471.1992 article EN Journal of Virology 1992-09-01

ABSTRACT The intestinal tract is a lymphocyte-rich site that undergoes severe depletion of memory CD4 + T cells within days simian immunodeficiency virus or human type 1 (HIV-1) infection. An ensuing influx virus-specific CD8 cells, which persist throughout the chronic phase infection, has also been documented in gastrointestinal tract. However, little known functionality these effector their relationship to disease course. In this study, we measured T-cell responses HIV-1 peptides paired...

10.1128/jvi.02535-06 article EN Journal of Virology 2007-03-08

Infection with HIV-1 results in marked immunologic insults and structural damage to the intestinal mucosa, including compromised barrier function. While development of highly active antiretroviral therapy (HAART) has been a major advancement treatment infection, need for novel complementary interventions help restore functional integrity remains unmet. Known properties pre-, pro-, synbiotics suggest that they may be useful tools achieving this goal.This was 4-week parallel,...

10.1186/1472-6882-12-84 article EN cc-by BMC Complementary and Alternative Medicine 2012-06-29

Previous studies have suggested that polyfunctional mucosal CD8(+) T-cell responses may be a correlate of protection in HIV controllers. Mucosal breadth and/or specificity also contribute to defining protective responses. In this study, rectal Gag, Env, and Nef were mapped at the peptide level four subject groups: elite controllers (n = 16; viral load [VL], <75 copies/ml), viremic 14; VL, 75 2,000 noncontrollers >10,000 antiretroviral-drug-treated subjects 8; copies/ml). all groups,...

10.1128/jvi.00803-10 article EN Journal of Virology 2010-07-29

Tissue-resident memory (TRM) CD8+ T-cells are non-recirculating, long-lived cells housed in tissues that can confer protection against mucosal pathogens. Human immunodeficiency virus-1 (HIV-1) is a pathogen and the gastrointestinal tract an important site of viral pathogenesis transmission. Thus, TRM may be effector subset for controlling HIV-1 tissues. This study sought to determine abundance, phenotype, functionality context chronic infection. We found majority rectosigmoid were...

10.1038/mi.2017.96 article EN cc-by-nc-nd Mucosal Immunology 2017-11-15
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