Productive Infection (productive + infection)

Distribution by Scientific Domains

Selected Abstracts

Productive human immunodeficiency virus-1 infection of epithelial cell lines of salivary gland origin

Y. Han
To ascertain whether epithelial cells of oral cavity origin may be infected with human immunodeficiency virus (HIV-1), a study to determine susceptibility to infection of salivary gland epithelial cell lines (HSY and HSG) was undertaken. Because of the potential for oral-genital transmission, an endometrial cell line, HEC-1, was also studied. Epithelial cell monolayers were infected with cell-free HTLVIIIB or a primary HIV-1 isolate. Several lines of evidence indicated that inoculation of these cell lines with HIV-1 led to productive infection: 1) p24 antigen was present in supernatants, with levels peaking on days 3,4; 2) provirus was found in cells by polymerase chain reaction; 3) virions present in supernatants were infectious as confirmed by coculture with the T-lympho- blastoid line CEM-NKr. Following a period of virus production, HIV-1 entered a latency phase over 10 weeks. All epithelial cell lines were positive for galactosylceramide (GalC) and CXCR4. HSY was weakly positive for surface CD4, and also expressed mRNA for CD4 and CCR5, as did HEC-1. Blocking studies indicated that anti-GalC, but not anti-CD4, significantly reduced productive infection, and that regulated on activation normal T cell expressed and secreted (RANTES) but not stromal cell,derived factor (SDF-1) could partially block infection of the M-tropic primary isolate. These results suggest that epithelial cells in the oral cavity and the genital tract might be targets of HIV-1 and potentially serve as a mediator of systemic infection. [source]

Mathematical modelling of the impact of haematopoietic stem cell-delivered gene therapy for HIV

John M. Murray
Abstract Background Gene therapy represents a new treatment paradigm for HIV that is potentially delivered by a safe, once-only therapeutic intervention. Methods Using mathematical modelling, we assessed the possible impact of autologous haematopoietic stem cell (HSC) delivered, anti-HIV gene therapy. The therapy comprises a ribozyme construct (OZ1) directed to a conserved region of HIV-1 delivered by transduced HSC (OZ1+HSC). OZ1+HSC contributes to the CD4+ T lymphocyte and monocyte/macrophage cell pools that preferentially expand under the selective pressure of HIV infection. The model was used to predict the efficacy of OZ1 in a highly active antiretroviral therapy (HAART) naÔve individual and a HAART-experienced individual undergoing two structured treatment operations. In the standard scenario, OZ1+HSC was taken as 20% of total body HSC. Results For a HAART-naÔve individual, modelling predicts a reduction of HIV RNA at 1 and 2 years post-OZ1 therapy of 0.5 log10 and 1 log10, respectively. Eight years after OZ1 therapy, the CD4+ T-lymphocyte count was 271 cells/mm3 compared to 96 cells/mm3 for an untreated individual. In a HAART-experienced individual HIV RNA was reduced by 0.34 log10 and 0.86 log10 at 1 and 2 years. The OZ1 effect was maximal when both CD4+ T lymphocytes and monocytes/macrophages were protected from successful, productive infection by OZ1. Conclusions The modelling indicates a single infusion of HSC cell-delivered gene therapy can impact on HIV viral load and CD4 T-lymphocyte count. Given that gene therapy avoids the complications associated with HAART, there is significant potential for this approach in the treatment of HIV. Copyright © 2009 John Wiley & Sons, Ltd. [source]

Unique Susceptibility of the Fetal Thymus to Feline Immunodeficiency Virus Infection: An Animal Model for HIV Infection In Utero1

PROBLEM: Human infants infected in utero with HIV develop thymus insufficiency and progress to AIDS sooner than infants infected peripartum. However, direct analysis of the thymus is difficult due to limited tissue access and variable timing of vertical transmission. METHOD OF STUDY: Fetal and neonatal cats were inoculated with feline immunodeficiency virus (FIV) at an equivalent infectious dose. The thymus, blood, and lymph nodes were harvested and compared at 23 and 46 days post-inoculation (p.i.) and also compared to sham-inoculated, age-matched controls. Lymphocyte phenotypes were analyzed by flow cytometry and virus burden was quantified in histologic sections and by virus isolation from plasma. RESULTS: Fetal cats inoculated with FIV had acute thymus atrophy at birth, which coincided with peak viremia. At 46 days p.i., thymus size and cell composition rebounded and supported increased productive infection. In contrast, neonatal cats inoculated with FIV developed chronic thymus atrophy and degeneration, which was associated with decreasing productive infection and low-level viremia. CONCLUSIONS: The fetal thymus is uniquely vulnerable to acute, transient depletion and high-level productive infection. The neonatal thymus is less vulnerable to acute changes, and responds through progressive atrophy and declining productive infection. Reduced immune competence, as reflected by the failure to control virus replication, may contribute to the accelerated progression of FIV and HIV infections in utero. [source]

BK Polyoma Virus Allograft Nephropathy: Ultrastructural Features from Viral Cell Entry to Lysis

Cinthia B Drachenberg
BK virions must enter the host cell and target their genome to the nucleus in order to complete their life cycle. The mechanisms by which the virions accomplish these tasks are not known. In this morphological study we found that BK virions localized beneath the host cell cytoplasmic membrane in 60,70-nm, smooth (non-coated) monopinocytotic vesicles similar to, or consistent with, caveolae. In the cytoplasm, the monopinocytotic vesicles carrying virions appeared to fuse with a system of smooth, vesicles and tubules that communicated with the rough endoplasmic reticulum and was continuous with the Golgi system. Membrane-bound single virions and large tubulo-reticular complexes loaded with virions accumulated in paranuclear locations. Occasional nuclei displayed virions within the perinuclear cisterna in association to the perinuclear viral accumulations. Tubular cells with mature productive infection had large nuclei, distended by daughter virions, whereas they lacked significant numbers of cytoplasmic virions. In addition to virally induced cell necrosis, there was extensive tubular cell damage (apoptosis and necrosis) in morphologically non-infected tubules. The observed ultrastructural interactions between the BK virions and host cells are remarkably similar to viral cell entry and nuclear targeting described for SV40 virus. [source]

Characterization of the porcine transferrin gene (TF,) and its association with disease severity following an experimental Actinobacillus pleuropneumoniae infection

E. Dani, owicz
Summary Transferrin (TF)-mediated provision of iron is essential for a productive infection by many bacterial pathogens, and iron-depletion of TF is a first line defence against bacterial infections. Therefore, the transferrin (TF) gene can be considered a candidate gene for disease resistance. We obtained the complete DNA sequence of the porcine TF gene, which spans 40 kb and contains 17 exons. We identified polymorphisms on a panel of 10 different pig breeds. Comparative intra- and interbreed sequence analysis revealed 62 polymorphisms in the TF gene including one microsatellite. Ten polymorphisms were located in the coding sequence of the TF gene. Four SNPs (c.902A>T, c.980G>A, c.1417A>G, c.1810A>C) were predicted to cause amino acid exchanges (p.Lys301Ile, p.Arg327Lys, p.Lys473Glu, p.Asn604His). We performed association analyses using six selected TF markers and 116 pigs experimentally infected with Actinobacillus pleuropneumoniae serotype 7. The analysis showed breed-specific TF allele frequencies. In German Landrace, we found evidence for a possible association of the severity of A. pleuropneumoniae infection with TF genotypes. [source]

Fulminant JC virus encephalopathy with productive infection of cortical pyramidal neurons,

Christian WŁthrich PhD
The polyomavirus JC (JCV) is the causative agent of progressive multifocal leukoencephalopathy and of JCV granule cell neuronopathy. We present a human immunodeficiency virus,negative patient who experienced development of multiple cortical lesions, aphasia, and progressive cognitive decline after chemotherapy for non,small-cell lung cancer. Brain biopsy and cerebrospinal fluid polymerase chain reaction demonstrated JCV, and she had a rapidly fatal outcome. Postmortem analysis showed diffuse cortical lesions and areas of necrosis at the gray,white junction. Immunostaining showed a productive JCV infection of cortical pyramidal neurons, confirmed by electron microscopy, with limited demyelination. This novel gray matter syndrome expands the scope of JCV clinical presentation and pathogenesis. Ann Neurol 2009;65:742,748 [source]

Human Immunodeficiency Virus Infection of the Brain: Pitfalls in Evaluating Infected/Affected Cell Populations

Stephanie J. Bissel
Monocyte/macrophages and CD4 T-cells are the primary hematopoietic targets of productive HIV infection. In the brain, potential cellular targets for HIV infection include perivascular and parenchymal macrophages/microglia, oligodendrocytes, endothelia, neurons, and astrocytes. We examine evidence of productive and non-productive infection for each cell type in the brains of HIV-infected patients with and without HIV encephalitis. Despite the voluminous literature and substantial experimental effort over the past two decades, evidence for productive infection of any brain cell other than macrophages is left wanting. [source]

Human cytomegalovirus induces a direct inhibitory effect on antigen presentation by monocyte-derived immature dendritic cells

Ulrich Grigoleit
Summary. The hypothesis that productive infection of monocyte-derived immature dendritic cells (DCs) by the human cytomegalovirus (HCMV) is associated with decreased immunostimulatory capacity was tested in this study. DCs were infected with 60,80% efficiency by HCMV strain TB40/E. Infected versus uninfected cells were analysed by fluorescence-activated cell sorting and by immunocytochemistry for surface expression of major histocompatibility complex (MHC) and co-stimulatory molecules as well as cytokine secretion during the 3 d after infection. The immunostimulatory capacity of these cells was measured by mixed leucocyte reaction. In spite of the fact that HCMV infection of DCs induced an increased release of tumour necrosis factor-, (TNF-,) and a decreased interleukin 10 (IL-10) production, expression of MHC class I and II, as well as CD40 and CD80 molecules, were downregulated on infected DCs. The mixed leucocyte reaction showed significantly reduced immunostimulatory capacity of infected DC cultures. Simultaneous detection of MHC antigens and virus antigens by double immunofluorescence revealed that downregulation occurred only on infected cells, but not on uninfected bystander cells. These findings demonstrate on a single cell level, together with the marked downregulation of MHC and co-stimulatory molecules in the presence of high TNF-, and low IL-10 levels, a direct inhibitory effect of HCMV on antigen presentation by immature DCs independent of soluble mediators. [source]