A5059938846- HIV Research and Treatment
- Immune Cell Function and Interaction
- Herpesvirus Infections and Treatments
- Cytomegalovirus and herpesvirus research
- HIV/AIDS drug development and treatment
- HIV/AIDS Research and Interventions
- DNA Repair Mechanisms
- Heat shock proteins research
- Nuclear Structure and Function
- Animal Virus Infections Studies
- Virus-based gene therapy research
- Mosquito-borne diseases and control
- Viral Infections and Immunology Research
- Immunodeficiency and Autoimmune Disorders
- Bacteriophages and microbial interactions
- Histone Deacetylase Inhibitors Research
- Immune responses and vaccinations
- Carcinogens and Genotoxicity Assessment
- Epigenetics and DNA Methylation
- Tuberculosis Research and Epidemiology
- Enzyme Structure and Function
- Animal Disease Management and Epidemiology
- Protein Structure and Dynamics
- Virology and Viral Diseases
- Toxin Mechanisms and Immunotoxins
Leidos Biomedical Research Inc. (United States)
2014-2025
Leidos (United States)
2014-2025
Pancreatic Cancer Action Network
2019-2021
National Cancer Institute
2004-2018
Frederick National Laboratory for Cancer Research
2014-2018
Science Applications International Corporation (United States)
2004-2013
Abstract Histone deacetylase (HDAC) inhibitors are undergoing clinical evaluation for cancer therapy. Because HDAC modulates chromatin structure and gene expression, parameters considered to influence radioresponse, we have investigated the effects of inhibitor MS-275 on radiosensitivity two human tumor cell lines (DU145 prostate carcinoma U251 glioma). Acetylation status histones H3 H4 was determined as a function time after addition removal from culture medium. acetylation increased by 6 h...
HIV-1-specific broadly neutralizing antibodies (bNAbs) can protect rhesus monkeys against simian-human immunodeficiency virus (SHIV) challenge. However, the site of antibody interception and mechanism antibody-mediated protection remain unclear. We administered a fully protective dose bNAb PGT121 to challenged them intravaginally with SHIV-SF162P3. In PGT121-treated animals, we detected low levels viral RNA DNA in distal tissues for seven days following Viral RNA-positive showed...
HIV and SIV infection dynamics are commonly investigated by measuring plasma viral loads. However, this total load value represents the sum of many individual events, which difficult to independently track using conventional sequencing approaches. To overcome challenge, we generated a genetically tagged virus stock (SIVmac239M) with 34-base genetic barcode inserted between vpx vpr accessory genes infectious molecular clone SIVmac239. Next-generation identified at least 9,336 barcodes, or...
Because of the potential for affecting multiple signaling pathways, inhibition Hsp90 may provide a strategy enhancing tumor cell radiosensitivity. Therefore, we have investigated effects orally bioavailable inhibitor 17-(dimethylaminoethylamino)-17-demethoxygeldanamycin (17-DMAG) on radiosensitivity human cells in vitro and grown as xenografts.The effect 17-DMAG levels three proteins (Raf-1, ErbB2, Akt) previously implicated regulation was determined solid lines. A clonogenic assay then used...
Reduction/elimination of HIV-1 reservoirs that persist despite combination antiretroviral therapy (cART) will likely require induction viral expression by residual infected cells and enhanced clearance these cells. TLR7 agonists have potential to mediate activities. We evaluated immunologic virologic effects repeated doses the agonist GS-9620 in SIV-infected rhesus macaques receiving cART, which was initiated at 13 days after infection continued for 75 weeks prior administration. During...
ABSTRACT Following mucosal human immunodeficiency virus type 1 transmission, systemic infection is established by one or only a few viral variants. Modeling single-variant, transmission in nonhuman primates using limiting-dose inoculations with diverse simian isolate stock may increase variability between animals since individual variants within the have substantial functional differences. To decrease while retaining ability to enumerate transmitted/founder sequence analysis, we modified...
ABSTRACT Our goal is to develop a pediatric combination vaccine protect the vulnerable infant population against human immunodeficiency virus type 1 (HIV-1) and tuberculosis (TB) infections. The consists of an auxotroph Mycobacterium strain that coexpresses HIV antigens. Utilizing rhesus macaque model, we have previously shown this attenuated M. (A Mtb )-simian (SIV) immunogenic, although did not prevent oral SIV infection, subset vaccinated animals was able partially control replication....
A vaccine is widely regarded as necessary for the control of HIV pandemic and eventual eradication AIDS. Neutralizing antibodies MHC-E-restricted CD8+ T cells have both been shown capable providing protection against simian counterpart HIV, SIV, in rhesus macaques. Here we provide preliminary evidence that combining these orthogonal antiviral mechanisms can increased SIV challenge such replication arrest observed following vaccination with a cytomegalovirus (RhCMV/SIV)-based was enhanced...
Simian immunodeficiency virus (SIV) challenge of rhesus macaques (RMs) vaccinated with strain 68–1 Rhesus Cytomegalovirus (RhCMV) vectors expressing SIV proteins (RhCMV/SIV) results in a binary outcome: stringent control and subsequent clearance highly pathogenic ~55% RMs no protection the remaining 45%. Although previous work indicates that unconventionally restricted, SIV-specific, effector-memory (EM)-biased CD8 + T cell responses are necessary for efficacy, magnitude these does not...
The effectiveness of virus-specific strategies, including administered HIV-specific mAbs, to target cells that persistently harbor latent, rebound-competent HIV genomes during combination antiretroviral therapy (cART) has been limited by inefficient induction viral protein expression. To examine antibody-mediated reservoir targeting without a need for induction, we used an anti-CD4 mAb deplete both infected and uninfected CD4+ T cells. Ten rhesus macaques with barcoded SIVmac239M received...
Although effective for suppressing viral replication, combination antiretroviral treatment (cART) does not represent definitive therapy HIV infection due to persistence of replication-competent reservoirs. The advent cART regimens simian immunodeficiency virus (SIV)-infected nonhuman primates (NHP) has enabled the development relevant models studying reservoirs and intervention strategies targeting them. Viral reservoir measurements are crucial such studies but problematic. Quantitative...
Abstract Simian immunodeficiency virus (SIV) challenge of rhesus macaques (RMs) vaccinated with Rhesus Cytomegalovirus (RhCMV) vectors expressing SIV proteins (RhCMV/SIV) results in a binary outcome: stringent control and subsequent clearance highly pathogenic ~55% RMs no protection the remaining 45%. Although previous work suggests that unconventionally restricted, SIV-specific, effector-memory (EM)-biased CD8 + T cell responses are necessary for efficacy, magnitude these does not predict...