Paul A Luciw

University of California, Davis, Davis, California, United States

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Publications (187)1144.05 Total impact

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    ABSTRACT: Persistent HIV replication within active viral reservoirs may be caused by inadequate antiretroviral penetration. Here, we utilize mass spectrometry imaging using infrared matrix-assisted laser desorption electrospray ionization to quantify efavirenz distribution within tissues from a macaque dosed orally to steady-state. Intra-tissue EFV distribution was heterogeneous, concentrating in the lamina propria of the colon, the primary follicles of lymph nodes, and brain grey matter. These are the first imaging data of antiretrovirals in active viral reservoirs. Copyright © 2015, American Society for Microbiology. All Rights Reserved.
    No preview · Article · Mar 2015 · Antimicrobial Agents and Chemotherapy
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    ABSTRACT: Multiplex methodologies, especially those with high-throughput capabilities generate large volumes of data. Accumulation of such data (e.g., genomics, proteomics, metabolomics etc.) is fast becoming more common and thus requires the development and implementation of effective data mining strategies designed for biological and clinical applications. Multiplex microbead immunoassay (MMIA), on xMAP or MagPix platform (Luminex), which is amenable to automation, offers a major advantage over conventional methods such as Western blot or ELISA, for increasing the efficiencies in serodiagnosis of infectious diseases. MMIA allows detection of antibodies and/or antigens efficiently for a wide range of infectious agents simultaneously in host blood samples, in one reaction vessel. In the process, MMIA generates large volumes of data. In this report we demonstrate the application of data mining tools on how the inherent large volume data can improve the assay tolerance (measured in terms of sensitivity and specificity) by analysis of experimental data accumulated over a span of two years. The combination of prior knowledge with machine learning tools provides an efficient approach to improve the diagnostic power of the assay in a continuous basis. Furthermore, this study provides an in-depth knowledge base to study pathological trends of infectious agents in mouse colonies on a multivariate scale. Data mining techniques using serodetection of infections in mice, developed in this study, can be used as a general model for more complex applications in epidemiology and clinical translational research.
    Full-text · Article · Jan 2015 · PLoS ONE
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    ABSTRACT: Combat wound healing and resolution are highly affected by the resident microbial flora. We therefore sought to achieve comprehensive detection of microbial populations in wounds using novel genomic technologies and bioinformatics analyses. We employed a microarray capable of detecting all sequenced pathogens for interrogation of 124 wound samples from extremity injuries in combat-injured U.S. service members. A subset of samples was also processed via next-generation sequencing and metagenomic analysis. Array analysis detected microbial targets in 51% of all wound samples, with Acinetobacter baumannii being the most frequently detected species. Multiple Pseudomonas species were also detected in tissue biopsy specimens. Detection of the Acinetobacter plasmid pRAY correlated significantly with wound failure, while detection of enteric-associated bacteria was associated significantly with successful healing. Whole-genome sequencing revealed broad microbial biodiversity between samples. The total wound bioburden did not associate significantly with wound outcome, although temporal shifts were observed over the course of treatment. Given that standard microbiological methods do not detect the full range of microbes in each wound, these data emphasize the importance of supplementation with molecular techniques for thorough characterization of wound-associated microbes. Future application of genomic protocols for assessing microbial content could allow application of specialized care through early and rapid identification and management of critical patterns in wound bioburden.
    No preview · Article · May 2014 · Journal of clinical microbiology
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    ABSTRACT: Using an established non-human primate model, rhesus macaques were infected intravenously with a chimeric simian immunodeficiency virus consisting of SIVmac239 with the HIV-1 reverse transcriptase from clone HXBc2 (RT-SHIV). The impact of two enhanced (four and five drug) highly active antiretroviral therapies (HAART) on early viral decay and rebound were determined. The four-drug combination included an integrase inhibitor, L-870-812 (L-812), together with a three drug regimen including emtricitabine [(-)-FTC], tenofovir [TFV], and efavirenz [EFV]. The five-drug combination consisted of one analog for each of the four the DNA precursors (using TFV, (-)-FTC, (-)-β-D-(2R,4R)-1,3-dioxolane-2,6-diaminopurine [Amdoxovir®, DAPD], and zidovudine [AZT] together with EFV. A cohort treated with a three drug combination of (-)-FTC, TFV and EFV served as treated controls. Daily administration of three, four or five drug combination of antiretroviral agents was initiated (at week 6 or 8 after inoculation), continued up to week 50, and then followed by a rebound period. Plasma samples were collected routinely and drug levels monitored using LC-MS/MS. Viral loads were monitored with a standard TaqMan qRT-PCR assay. Comprehensive analyses of replication dynamics were performed. RT-SHIV infection in rhesus macaques produced typical viral infection kinetics with untreated controls establishing persistent viral loads of > 10(4) copies of RNA/mL. RT-SHIV viral loads at start of treatment (V0) were similar in all treated cohorts (p > 0.5). All antiretroviral drug levels were measureable in plasma. The four-drug and five-drug combination regimens (enhanced HAART) improved suppression of viral load (within one wk, p < 0.01) and had an overall greater potency (p < 0.02) than the three-drug regimen (HAART). Moreover, rebound viremia occurred rapidly following cessation of any treatment. The enhanced HAART (four- or five-drug combinations) had significant improvement in viral suppression compared to the three-drug combination, but no combination was sufficient to eliminate viral reservoirs.
    Full-text · Article · Apr 2014 · Antimicrobial Agents and Chemotherapy
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    ABSTRACT: Blast wounds often involve diverse tissue types and require substantial time and treatment for appropriate healing. Some of these subsequent wounds become colonized with bacteria requiring a better understanding of how the host responds to these bacteria and what proteomic factors contribute wound healing outcome. In addition, using reliable and effective proteomic sample preparation procedures can lead to novel biomarkers for improved diagnosis and therapy. To address this need, suitable sample preparation for 2-D DIGE proteomic characterization of wound effluent and serum samples from combat-wounded patients was investigated. Initial evaluation of crude effluent and serum proved the necessity of high abundant protein depletion. Subsequently, both samples were successfully depleted using Agilent Multiple Affinity Removal system and showed greatly improved 2-D spot maps, comprising 1,800 and 1,200 protein spots, respectively. High abundant protein removal was necessary for both wound effluent and serum. This is the first study to show a successful method for high abundant protein depletion from wound effluent which is compatible with downstream 2-D DIGE analysis. This development allows for improved biomarker discovery in wound effluent and serum samples.
    Full-text · Article · Feb 2014 · Proteome Science
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    ABSTRACT: Highly active antiretroviral therapy (HAART) can reduce levels of human immunodeficiency virus type 1 (HIV-1) to undetectable levels in infected individuals, but the virus is not eradicated. The mechanisms of viral persistence during HAART are poorly defined, but some reservoirs have been identified, such as latently infected resting memory CD4(+) T cells. During latency, in addition to blocks at the initiation and elongation steps of viral transcription, there is a block in the export of viral RNA (vRNA), leading to the accumulation of multiply-spliced transcripts in the nucleus. Two of the genes encoded by the multiply-spliced transcripts are Tat and Rev, which are essential early in the viral replication cycle and might indicate the state of infection in a given population of cells. Here, the levels of multiply-spliced transcripts were compared to the levels of gag-containing RNA in tissue samples from RT-SHIV-infected rhesus macaques treated with HAART. Splice site sequence variation was identified during development of a TaqMan PCR assay. Multiply-spliced transcripts were detected in gastrointestinal and lymphatic tissues, but not the thymus. Levels of multiply-spliced transcripts were lower than levels of gag RNA, and both correlated with plasma virus loads. The ratio of multiply-spliced to gag RNA was greatest in the gastrointestinal samples from macaques with plasma virus loads <50 vRNA copies per mL at necropsy. Levels of gag RNA and multiply-spliced mRNA in tissues from RT-SHIV-infected macaques correlate with plasma virus load.
    Full-text · Article · Feb 2014 · PLoS ONE
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    ABSTRACT: Tuberculosis (TB) in non-human primates (NHPs) is highly contagious, requiring efficient identification of animals infected with Mycobacterium tuberculosis. Tuberculin skin test is usually used but lacks desirable sensitivity/specificity and efficiency. We aimed to develop an immunoassay for plasma antibodies against M. tuberculosis. A key challenge is that not all infected animals contain antibodies against the same M. tuberculosis antigen. Therefore, a multiplex panel of 28 antigens (Luminex(®) -Platform) was developed. Data revealed antibodies against eight antigens (Rv3875, Rv3875-Rv3874 fusion, Rv3874, Rv0934, Rv3881, Rv1886c, Rv2031, Rv3841) in experimentally infected (M. tuberculosis strains: Erdman and H37Rv) NHPs (rhesus and cynomolgus macaques). In a naturally acquired M. tuberculosis infection, rhesus macaques (n = 15) with lung TB pathology (n = 10) contained antibodies to five additional antigens (Rv0831, Rv2220, Rv0054, Rv1099, and Rv0129c). Results suggest that this user-friendly and easily implementable multiplex panel, containing 13 M. tuberculosis antigens, may provide a high-throughput alternative for NHP TB screening.
    Full-text · Article · Jan 2014 · Journal of Medical Primatology
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    ABSTRACT: Multiplex microbead immunoassay (MMIA) is a powerful technology for a wide range of biomedical and clinical applications. It is important to study the normal concentration ranges of immunomodulators under different sample preparation conditions and age groups of subjects in order to more precisely determine their reference values for use in assessing alterations of their levels in disease. The aim of this study was to determine the plasma concentrations of immunomodulators (cytokines, chemokines and growth factors) in the peripheral blood from healthy subjects by the use of a large multiplex panel, and to determine the effects of different anticoagulants, age and gender on the immunomodulator levels. In addition, the assay precision for these biomarker analytes was determined. Plasma samples from 107 healthy subjects, aged 18-85 years, were collected in three different anticoagulants (sodium citrate, EDTA, Heparin); corresponding serum samples were also obtained. Multiplex microbead immunoassays were performed for measuring a total of 23 analytes including chemokines, cytokines and growth factors (IL-1β, IL-1ra, IL-2, IL-6, IL-7, IL-8, IL-12 p70, IL-17, IFN-γ, IP-10, MCP-1, PDGF-BB, RANTES, TNF-α, IL-1a, IL-16, HGF, MIG, TNF- β, PDGF-ABBB, EGF, Flt-3 Ligand, VEGF). For these analytes, our results showed that the anticoagulant affected the concentration measurements and the coefficients of variation. However, the relative levels of the analytes (profiles) of samples collected in a particular anticoagulant are consistent. The analytes IL-1 β, IL-7, Fit3-Ligand and IL-12p70 show the largest variation (up to four-fold) between the age groups. In addition, no statistically significant differences in the level of the analytes were found between the sexes. © 2013 Clinical Cytometry Society
    Full-text · Article · Dec 2013 · Cytometry Part B Clinical Cytometry
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    ABSTRACT: The ability to forecast whether a wound will heal after closure without further debridement(s), would provide substantial benefits to patients with severe extremity trauma. Wound effluent is a readily available material which can be collected without disturbing healthy tissue. For analysis of potential host response biomarkers, forty four serial combat wound effluent samples from 19 patients with either healing or failing traumatic- and other combat-related wounds were examined by 2-D DIGE. Spot map patterns were correlated to eventual wound outcome (healed or wound failure) and analyzed using DeCyder 7.0 and differential proteins identified via LC-MS/MS. This approach identified 52 protein spots that were differentially expressed and thus represent candidate biomarkers for this clinical application. Many of these proteins are intimately involved in inflammatory and immune responses. Furthermore, discriminate analysis further refined the 52 differential protein spots to a smaller subset of which successfully differentiate between wounds that will heal and those that will fail and require further surgical intervention with greater than 83% accuracy. These results suggest candidates for a panel of protein biomarkers that may aid traumatic wound care prognosis and treatment. We recommend that this strategy be refined, and then externally validated, in future studies of traumatic wounds.
    Full-text · Article · Nov 2013 · Journal of Translational Medicine
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    Full-text · Dataset · Aug 2013
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    ABSTRACT: Eradication of persistent intracellular bacterial pathogens with antibiotic therapy is often slow or incomplete. However, strategies to augment antibiotics are hampered by our poor understanding of the nutritional environment that sustains chronic infection. Here we show that the intracellular pathogen Brucella abortus survives and replicates preferentially in alternatively activated macrophages (AAMs), which are more abundant during chronic infection. A metabolic shift induced by peroxisome proliferator-activated receptor γ (PPARγ), which increases intracellular glucose availability, is identified as a causal mechanism promoting enhanced bacterial survival in AAMs. Glucose uptake was crucial for increased replication of B. abortus in AAMs, and for chronic infection, as inactivation of the bacterial glucose transporter gluP reduced both intracellular survival in AAMs and persistence in mice. Thus, a shift in intracellular nutrient availability induced by PPARγ promotes chronic persistence of B. abortus within AAMs, and targeting this pathway may aid in eradicating chronic infection.
    Full-text · Article · Aug 2013 · Cell host & microbe
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    ABSTRACT: Early secreted antigenic target protein 6 (esat6) is one of the genes present on region of difference 1 (RD1) of Mycobacterium tuberculosis (M. tb) genome. This RD1 is a characteristic of virulent strains of M. tb and Mycobacterium bovis and this is one of the major differences between the disease causing strains and Bacillus-Calmat Guerin (BCG) vaccine strains. Studies have proved the presence of large number of memory T cells in M. tb infected individuals and these memory cells are reactive towards Esat6 antigen, which highlighted the importance of this gene especially in early infections. In this study, numbers of esat6 gene constructs were made in order to get a suitable construct to be used as good DNA vaccine. First esat6 gene construct was made in pND vector without Kozak sequence upstream the gene, second construct was made in pcDNA3.1 vector with Kozak sequence upstream the gene, third construct was made again in pND vector with Kozak sequence, fourth construct was made with Kozak sequence upstream and GGG downstream the ATG as a second codon of gene first in pcDNA3.1 and later in pND vectors respectively which was designated as construct five. Sixth construct was a fusion and in pcDNA3.1 vector with Kozak upstream the gene and epitope V and poly histidine tail sequence provided by vector down stream the gene through in-frame cloning of esat6 gene with sequences provided by vector by removing stop codon through PCR based primers. Seventh and final construct was prepared in pND14 vector also as a fusion construct and gene was cloned under tissue plasminogen activator sequence in an in-frame through PCR based primers. All these constructs were subjected to 293T human embryonic kidney cell lines to evaluate their level of expression. Although none of the constructs gave detectable level of expression in cultured cells when tested through Western blots (WB) but tpa-esat6-pND14 construct was selected as potential DNA vaccine candidate to inject intramuscularly and interadermally to balb/c mice along with controls to obtain detectable response in vivo. Animals were tested nine weeks post vaccination and found positive against tpa-esat6-pND14 vaccine through WB and multiplex micro bead immunoassay (MMIA).
    Full-text · Article · Jul 2013 · Pakistan journal of zoology
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    ABSTRACT: Host immune responses to Mycobacterium tuberculosis (M. tb.) are generally able to contain infection and maintain a delicate balance between protection and immunopathology. A shift in this balance appears to underlie active disease observed in about ten percent of infected individuals. Effects of local inflammation, combined with anti-M. tb. systemic immune responses, are directly detectable in peripheral circulation, without ex vivo stimulation of blood cells or biopsy of the affected organs. We studied plasma immunomodulator and antibody biomarkers in patients with active pulmonary TB by a combination of multiplex microbead immunoassays and computational tools for data analysis. Plasma profiles of ten immunomodulators and antibodies against eight M. tb. antigens (previously reported by us) were examined in active pulmonary TB patients in a TB endemic country, Pakistan. Multiplex analyses were performed on samples from apparently healthy individuals, without active TB, from the same community as the TB patients to establish the assay baselines for all analytes. Over three thousand data points were collected from patients (n=135) and controls (n=37). The data were analyzed by multivariate and computer assisted cluster analyses to reveal patterns of plasma immunomodulators and antibodies. This study shows plasma profiles that in most patients represented either strong antibody or strong immunomodulator biomarkers. Profiling of a combination of both immunomodulators and antibodies described here may be valuable for the analysis of host immune responses in active TB in endemic countries.
    Full-text · Article · Jun 2013 · Clinical and vaccine Immunology: CVI
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    ABSTRACT: FIV establishes a latent infection in peripheral CD4+ T-cells, and the latent FIV promoter is associated with deacetylated, methylated histones, consistent with a restrictive chromatin structure. Here we explored the use of 5 histone-modifying agents - 4 histone deacetylase inhibitors (HDACi) and 1 histone methyltransferase inhibitor (HMTi) - to reactivate latent FIV ex vivo. All compounds tested were able to alter histone lysine residue modifications in feline cells, both globally and at the FIV promoter locally. When latently FIV-infected peripheral CD4+ T-cells were cultured ex vivo in the presence of these inhibitors, viral transcription was significantly activated relative to no treatment controls. Transcriptional reactivation of virus mediated by the HDACi suberoylanilide hydroxamic acid (SAHA) was dose-dependent, detected after as little as 1h of exposure, and resulted in virion formation as evidenced by supernatant reverse transcriptase activity. A synergistic effect was not found when SAHA was combined with HMTi under the conditions tested. At low therapeutically relevant concentrations in primary feline PBMC, SAHA was found to be minimally cytotoxic and non-immune activating. HDACi and HMTi can reactivate latent FIV ex vivo, and SAHA, also known as the anticancer drug Vorinostat, in particular is a promising candidate for in vivo use because of its efficacy, potency, and relative safety. Use of the FIV/cat model of lentiviral latency to explore in vivo treatment with SAHA and other anti-latency therapeutics will allow investigations that are either ethically or logistically not addressable in patients persistently infected with human immunodeficiency virus (HIV-1).
    No preview · Article · Oct 2012 · Virus Research
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    Full-text · Article · Sep 2012 · Retrovirology
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    ABSTRACT: Infection with HIV-1 results in marked immunologic insults and structural damage to the intestinal mucosa, including compromised barrier function. While the development of highly active antiretroviral therapy (HAART) has been a major advancement in the treatment of HIV-1 infection, the need for novel complementary interventions to help restore intestinal structural and functional integrity remains unmet. Known properties of pre-, pro-, and synbiotics suggest that they may be useful tools in achieving this goal. This was a 4-week parallel, placebo-controlled, randomized pilot trial in HIV-infected women on antiretroviral therapy. A synbiotic formulation (Synbiotic 2000®) containing 4 strains of probiotic bacteria (10(10) each) plus 4 nondigestible, fermentable dietary fibers (2.5 g each) was provided each day, versus a fiber-only placebo formulation. The primary outcome was bacterial translocation. Secondary outcomes included the levels of supplemented bacteria in stool, the activation phenotype of peripheral T-cells and monocytes, and plasma levels of C-reactive protein and soluble CD14. Microbial translocation, as measured by plasma bacterial 16S ribosomal DNA concentration, was not altered by synbiotic treatment. In contrast, the synbiotic formulation resulted in significantly elevated levels of supplemented probiotic bacterial strains in stool, including L. plantarum and P. pentosaceus, with the colonization of these two species being positively correlated with each other. T-cell activation phenotype of peripheral blood lymphocytes showed modest changes in response to synbiotic exposure, with HLA-DR expression slightly elevated on a minor population of CD4+ T-cells which lack expression of HLA-DR or PD-1. In addition, CD38 expression on CD8+ T-cells was slightly lower in the fiber-only group. Plasma levels of soluble CD14 and C-reactive protein were unaffected by synbiotic treatment in this study. Synbiotic treatment for 4 weeks can successfully augment the levels of probiotic species in the gut during chronic HIV-1 infection. Associated changes in microbial translocation appear to be absent, and markers of systemic immune activation appear largely unchanged. These findings may help inform future studies aimed at testing pre- and probiotic approaches to improve gut function and mucosal immunity in chronic HIV-1 infection. Clinical NCT00688311.
    Full-text · Article · Jun 2012 · BMC Complementary and Alternative Medicine
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    ABSTRACT: Many resource-poor countries are faced with concurrent epidemics of AIDS and tuberculosis (TB) caused by human immunodeficiency virus (HIV) and Mycobacterium tuberculosis, respectively. Dual infections with HIV and M. tuberculosis are especially severe in infants. There is, however, no effective HIV vaccine, and the only licensed TB vaccine, the Mycobacterium bovis bacillus Calmette-Guérin (BCG) vaccine, can cause disseminated mycobacterial disease in HIV-infected children. Thus, a pediatric vaccine to prevent HIV and M. tuberculosis infections is urgently needed. We hypothesized that a highly attenuated M. tuberculosis strain containing HIV antigens could be safely administered at birth and induce mucosal and systemic immune responses to protect against HIV and TB infections, and we rationalized that vaccine safety could be most rigorously assessed in immunocompromised hosts. Of three vaccine candidates tested, the recombinant attenuated M. tuberculosis strain mc(2)6435 carrying a simian immunodeficiency virus (SIV) Gag expression plasmid and harboring attenuations of genes critical for replication (panCD and leuCD) and immune evasion (secA2), was found to be safe for oral or intradermal administration to non-SIV-infected and SIV-infected infant macaques. Safety was defined as the absence of clinical symptoms, a lack of histopathological changes indicative of M. tuberculosis infection, and a lack of mycobacterial dissemination. These data represent an important step in the development of novel TB vaccines and suggest that a combination recombinant attenuated M. tuberculosis-HIV vaccine could be a safe alternative to BCG for the pediatric population as a whole and, more importantly, for the extreme at-risk group of HIV-infected infants.
    Full-text · Article · Jun 2012 · Clinical and vaccine Immunology: CVI
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    ABSTRACT: Rapid detection and therapeutic intervention for infectious and emerging diseases is a major scientific goal in biodefense and public health. Toward this end, cytokine profiles in human blood were investigated using a human whole blood ex vivo exposure model, called WEEM. Samples of whole blood from healthy volunteers were incubated with seven pathogens including Yersinia pseudotuberculosis, Yersinia enterocolitica, Bacillus anthracis, and multiple strains of Yersinia pestis, and multiplexed protein expression profiling was conducted on supernatants of these cultures with an antibody array to detect 30 cytokines simultaneously. Levels of 8 cytokines, IL-1α, IL-1β, IL-6, IL-8, IL-10, IP-10, MCP-1 and TNFα, were significantly up-regulated in plasma after bacterial exposures of 4 hours. Statistical clustering was applied to group the pathogens based on the host response protein expression profiles. The nearest phylogenetic neighbors clustered more closely than the more distant pathogens, and all seven pathogens were clearly differentiated from the unexposed control. In addition, the Y. pestis and Yersinia near neighbors were differentiated from the B. anthracis strains. Cluster analysis, based on host response cytokine profiles, indicates that distinct patterns of immunomodulatory proteins are induced by the different pathogen exposures and these patterns may enable further development into biomarkers for diagnosing pathogen exposure.
    Preview · Article · May 2012 · BMC Microbiology
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    ABSTRACT: Feline immunodeficiency virus (FIV), the lentivirus of domestic cats responsible for feline AIDS, establishes a latent infection in peripheral blood CD4+ T-cells approximately eight months after experimental inoculation. In this study, cats experimentally infected with the FIV-C strain in the asymptomatic phase demonstrated an estimated viral load of 1 infected cell per approximately 10(3) CD4+ T-cells, with about 1 copy of viral DNA per cell. Approximately 1 in 10 proviral copies was capable of transcription in the asymptomatic phase. The latent FIV proviral promoter was associated with deacetylated, methylated histones, which is consistent with a condensed chromatin structure. In contrast, the transcriptionally active FIV promoter was associated with histone acetylation and demethylation. In addition, RNA polymerase II appeared to be paused on the latent viral promoter, and short promoter-proximal transcripts were detected. Our findings for the FIV promoter in infected cats are similar to results obtained in studies of human immunodeficiency virus (HIV)-1 latent proviruses in cell culture in vitro studies. Thus, the FIV/cat model may offer insights into in vivo mechanisms of HIV latency and provides a unique opportunity to test novel therapeutic interventions aimed at eradicating latent virus.
    Full-text · Article · May 2012 · Viruses
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    ABSTRACT: Feline immunodeficiency virus (FIV) is a lentivirus of cats that establishes a lifelong persistent infection with immunologic impairment. In an approximately 2 year-long experimental infection study, cats infected with a biological isolate of FIV clade C demonstrated undetectable plasma viral loads from 10 months post-infection onward. Viral DNA was detected in CD4+CD25+ and CD4+CD25- T cells isolated from infected cats whereas viral RNA was not detected at multiple time points during the early chronic phase of infection. Viral transcription could be reactivated in latently infected CD4+ T cells ex vivo as demonstrated by detectable FIV gag RNA and 2-long terminal repeat (LTR) circle junctions. Viral LTR and gag sequences amplified from peripheral blood mononuclear cells during early and chronic stages of infection demonstrated minimal to no viral sequence variation. Collectively, these findings are consistent with FIV latency in peripheral blood CD4+ T cells isolated from chronically infected cats. The ability to isolate latently FIV-infected CD4+ T lymphocytes from FIV-infected cats provides a platform for the study of in vivo mechanisms of lentiviral latency.
    Full-text · Article · Feb 2012 · Retrovirology

Publication Stats

12k Citations
1,144.05 Total Impact Points


  • 1985-2015
    • University of California, Davis
      • • Center for Comparative Medicine
      • • Department of Pathology and Laboratory Medicine
      • • School of Medicine
      • • Department of Plant Pathology
      Davis, California, United States
  • 2010
    • California State University, Sacramento
      Sacramento, California, United States
  • 2005
    • University of Houston
      Houston, Texas, United States
  • 2002
    • Claude Bernard University Lyon 1
      Villeurbanne, Rhône-Alpes, France
  • 1983-2002
    • University of California, San Francisco
      • Department of Microbiology and Immunology
      San Francisco, California, United States
  • 1993
    • University of Freiburg
      Freiburg, Baden-Württemberg, Germany
  • 1990
    • Tel Aviv University
      Tell Afif, Tel Aviv, Israel
  • 1988-1989
    • Howard Hughes Medical Institute
      Ashburn, Virginia, United States
    • Salk Institute
      • Molecular Biology and Virology Laboratory
      La Jolla, California, United States
  • 1987-1989
    • Centers for Disease Control and Prevention
      • Division of Viral Diseases
      Атланта, Michigan, United States