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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The localization of HIV-1 proviruses in compositional DNA fractions from 27 AIDS patients during the chronic phase of the disease with depletion of CD4+ and different levels of viremia showed the following. (1) At low viremia, proviruses are predominantly localized in the GC-richest isochores, which are characterized by an open chromatin structure; this result mimics findings on HIV-1 integration in early infected cells in culture. (2) At higher viremia, an increased distribution of proviruses in GC-poor isochores (which match the GC poorness of HIV-1) was found; this suggests a selection of cells in which the 'isopycnic' localization leads to a higher expression of proviruses and, in turn, to higher viremia. (3) At the highest viremia, integrations in GC-rich isochores are often predominant again, but generally not at the same level as in (1); this may be the consequence of new integrations from the extremely abundant RNA copies.
Cell Mol Life Sci 2004 Mar
PMID:Distribution of HIV-1 in the genomes of AIDS patients. 1505 14

Human immunodeficiency virus type 1 (HIV-1) can infect circulating peripheral blood monocytes and resting CD4+ T lymphocytes despite sustained suppression of plasma viremia to undetectable levels. These persistently infected cell populations pose a barrier for virus eradication by highly active antiretroviral therapy (HAART), and are a significant reservoir of HIV-1 contributing to viral rebound following cessation or failure of HAART. This chapter provides a protocol for isolating replication-competent HIV-1 from peripheral blood monocytes of HIV-1-infected individuals, including those with sustained plasma HIV-1 RNA levels below 50 copies/mL, by co-culture with CD8-depleted, phytohemagglutinin-activated donor peripheral blood mononuclear cells. In our laboratory, this protocol has the sensitivity to achieve a success rate of positive HIV-1 isolation in approx 70% of cases. The study of HIV-1 strains harbored by peripheral blood monocytes of patients undergoing HAART will contribute to the understanding of viral persistence in cellular reservoirs that impede effective HAART.
Methods Mol Biol 2005
PMID:Isolation of human immunodeficiency virus type 1 from peripheral blood monocytes. 1606 64

The B19 virus can persist in immunocompromised patients for several months and sometimes even years because of impaired immune response. Viremia in persistent and recurrent infection may range from very low to high titers and may be associated with chronic clinical manifestations, such as chronic anemia. Several recently developed techniques that quantify B19-DNA have improved laboratory diagnosis of the infection and can help guide the choice of treatment in persistent infections (i.e., intravenous immunoglobulin (IVIG) treatment vs immunosuppression reduction). Here we describe the development of a reliable internally controlled quantitative competitive (QC)- polymerase chain reaction (PCR) assay that measures B19-DNA load in serum samples by densitometric analysis of the amplification products for monitoring B19 infection in high-risk patients. A retrospective quantification of B19-DNA in the serum samples from 48 anemic transplanted patients by the QC-PCR assay we developed in our laboratory confirmed the presence of B19-DNA in 11 of 48 samples and showed a viral DNA load between 103 and 108 B19-DNA copies/mL depending on the patients' serostatus (the highest viral load was found in IgM-positive/IgG-negative patients, that is, in patients with active B19 infection at onset). The assay also confirmed B19-DNA negative patients. Our QC-PCR assay may be easily used in monitoring B19 prototype DNA load to follow persistent infections and to better understand the relation between active B19 infection and occurrence of anemia and to assess the efficacy of IVIG therapy or immunosuppression reduction in clearing the virus in high-risk patients.
Mol Biotechnol 2006 Jan
PMID:Quantitative competitive-PCR assay to measure human parvovirus B19-DNA load in serum samples. 1638 79

Feline leukemia virus (FeLV) is a gamma retrovirus that induces fatal diseases in domestic cats. Efficacious FeLV vaccines prevent persistent viremia and development of FeLV-related disease after virus exposure, but not minimal viral replication and a provirus-positive state as recently demonstrated using sensitive real-time PCR assays. Proviral integration is an important parameter of latent infection and persistence of retroviruses in infected cells. So far, FeLV-specific real-time PCR assays could not distinguish between the integrated and episomal forms of the provirus. Thus, it was the aim of the present study to develop a rapid assay for the detection of FeLV proviral integration. The test combines conventional and quantitative real-time PCR that use virus-specific primers and primers specific for cat genomic small interspersed nuclear elements. It was applied to analyze the time course of proviral integration into the genome of a feline fibroblast cell line and detect provirus integration in peripheral white blood cells from vaccinated and unvaccinated, FeLV-exposed cats. The newly developed rapid test will essentially contribute to a better understanding of the mechanisms involved in the pathogenesis of FeLV infection and be especially useful in the development of antiretroviral vaccines and therapies aimed at the inhibition of proviral integration.
Mol Cell Probes
PMID:Rapid detection of feline leukemia virus provirus integration into feline genomic DNA. 1648 15

While the salivary gland has been recognized as an important effector site of the common mucosal immune system, a useful model for studying anti-viral salivary gland immune responses in vivo and for exploring the role of the salivary gland within the common mucosal system has been lacking. Murine cytomegalovirus (MCMV) is a beta-herpesvirus that displays a strong tropism for the salivary gland and produces significant morbidity in susceptible mice when introduced by intraperitoneal (i.p.) inoculation. This study tested the hypothesis that MCMV morbidity and pathology could be reduced by injecting the virus directly the submandibular salivary gland (intraglandular (i.g.)), using either in vivo derived MCMV or the less virulent, tissue-culture-derived MCMV (tcMCMV). Peak salivary gland viral titers were completely unaffected by infection route (i.p vs. i.g.) after inoculation with either MCMV or tcMCMV. However, i.g. tcMCMV inoculation reduced viremia in all systemic tissues tested compared to i.p. inoculation. Furthermore, systemic organ pathology observed in the liver and spleen after i.p. inoculation with either MCMV or tcMCMV was completely eliminated by i.g. inoculation with tcMCMV. Cellular infiltrates in the salivary glands, after i.p. or i.g. inoculation were composed of both B and T cells, indicating the potential for a local immune response to occur in the salivary gland. These results demonstrate that a focused MCMV infection of the salivary gland without systemic organ pathology is possible using i.g. delivery of tcMCMV.
Exp Mol Pathol 2007 Jun
PMID:A focused salivary gland infection with attenuated MCMV: an animal model with prevention of pathology associated with systemic MCMV infection. 1732 76

Similar to the human immunodeficiency virus (HIV), the hepatitis B virus (HBV) replicates via reverse transcription, in this case, within infected hepatocytes. Substantial advances have been achieved in the past ten years in developing and utilizing nucleoside/nucleotide analog drugs to inhibit HBV replication. Most are chain terminators that interfere with one or more steps in the replication cycle. Four of them (lamivudine, adefovir dipivoxil, entecavir, and telbivudine), have been approved by the United States Food and Drug Administration (FDA) for the treatment of chronic hepatitis B (CHB). In clinical trials of HBeAg positive and negative CHB patients, 48-52 week of treatment with these drugs can induce a 4-7 log decrease of HBV viremia and histological improvement. Long-term suppression of active HBV replication has been found to be associated with decreased inflammation, reversal of liver fibrosis and a lower incidence of hepatocellular carcinoma. However, permanent clearance of HBV is rarely achieved with current available antiviral agents, maintenance therapy being required for continuous suppression of HBV replication. In patients on continuous therapy, drug resistant mutations develop with all four drugs. Combination therapy with different nucleos(t)ide analog drugs or nucleos(t)ide drugs and pegylated interferon needs further clinical study. Newer promising nucleotide analog drugs with more potent antiviral efficacy are also under development.
Curr Mol Med 2007 Mar
PMID:Molecular mechanisms of resistance to antiviral therapy in patients with chronic hepatitis B. 1734 70

The aim of this study was the development of a real-time PCR for HIV DNA quantification in whole blood leucocytes providing an alternative assay to those already described, almost based on the gag gene detection. The technique (pbs-rtPCR assay) is more rapid (the whole assay required less than 5h), easy to perform, omitting both PBMC purification step and data normalization to a housekeeping gene, when compared to previously published assays. Our method is able to detect all group M HIV-1 subtypes in the highly conserved primer-binding site (PBS) region and to avoid the interference by retroviral endogenous sequences in HIV DNA quantification. The sensitivity was 100% for 2 copies even in the presence of high amounts of genomic DNA (1 microg). To monitor the HIV DNA level in all possible clinical conditions, the assay has been validated and compared with a previously developed gag-PCR assay on 73 HIV-1 HAART-treated patients with a plasma HIV-1 RNA range from <50 to >500,000 copies/ml. The 50% of the samples with a viremia below the limit of detection (50 copies/ml) was found to contain HIV DNA between 2 and 10 copies/microg DNA. The pbs-rtPCR offers a significant improvement in the percentage of quantitatively detectable sample (99%) compared with the gag-PCR (42%) suggesting caution in the choice of HIV DNA assay.
Mol Cell Probes
PMID:Fast and sensitive quantitative detection of HIV DNA in whole blood leucocytes by SYBR green I real-time PCR assay. 1762 50

Programmed death-1 (PD-1) is demonstrated to have an increased expression on antigen-specific T cells during chronic virus infections, and the blockage of PD-1/PD-ligand (PD-L1) pathway could restore the function of exhausted T cells. We measured the PD-1 expression levels on HBV-specific CD8 T cells and investigated the role of PD-1/PD-L1 pathway in T-cell responses of patients with different HBV infection statuses. Compared to the patients with convalescent acute hepatitis B, PD-1 expression on total CD8 T cells from chronic hepatitis B (CHB) patients was significantly upregulated, especially on the HBV pentamer-positive CD8 T cells. And PD-L1, but not PD-L2, was also significantly upregulated on PBMC from CHB patients. In CHB patients, HBV-specific T cells and cellular proliferation could be observed under the recombinant HBV-Ag stimulation in vitro, and blockade of PD-1 pathway significantly enhanced the IFN-gamma production and cellular proliferation of PBMC. Furthermore, PD-1 expression level on HBV-pentamers positive CD8 T cells was positively associated with plasma viral load in CHB patients. Thus, PD-1 upregulation on HBV-specific CD8 T cells is engaged in the dysfunction of T cells and high viraemia in CHB patients, and the antiviral T-cell responses could be improved by the blockade of this inhibitory PD-1/PD-L1 pathway.
Mol Immunol 2008 Feb
PMID:PD-1 upregulation is associated with HBV-specific T cell dysfunction in chronic hepatitis B patients. 1786 72

Human cytomegalovirus (HCMV) is a widespread agent causing a life-long persistent and generally asymptomatic infection in immunocompetent individuals. In contrast, immunocompromised subjects are the most susceptible group to experience HCMV disease. First genes to be expressed during the replication cycle are the immediate early (IE) genes, the products of which have pleiotropic effects on host cell metabolism. Aim of this study was to compare two set of primers in the optimization and standardization of a RT-PCR assay for qualitative detection of mRNA encoded by the IE gene UL123 (IE1). The RT-PCR assays were then used to evaluate the UL123 gene expression in 29 peripheral blood leukocyte (PBL) samples obtained from 14 renal transplant recipients. In particular, 21/29 (72.4%) were positive with set A of primers vs. 24/29 (82.8%) with set B. Only one sample were negative with set B and positive with set A. Twenty-four of 29 samples (82.8%) were pp65-antigaenemia positive: 21 mRNA-UL123 positive with set A vs. 22 with set B; all viraemia-positive patients were mRNA-UL123 positive with both set A and B. Five of 29 samples were pp65-antigaenemia negative: 1 mRNA-UL 123 positive with set A vs. 2 with set B; all of them were viraemia-negative. These two RT-PCR assays could provide a reliable, rapid and sensitive system enabling the detection and identification of UL123 transcripts and could be usefully employed to study the pathogenesis of HCMV-related diseases.
Mol Biotechnol 2008 Jan
PMID:Evaluation of two set of primers for detection of immediate early gene UL123 of human cytomegalovirus (HCMV). 1809 91

Natural killer cells are important in innate defense against viral infections. The interplay between stimulatory and inhibitory natural killer cell receptors and their corresponding human leukocyte antigen ligands are known to influence the outcome of acute Hepatitis C virus infection. Frequencies of NK receptor genes (8 inhibitory, 6 activating and 2 pseudogenes) and HLA class II alleles (DRB1, DQB1) were analyzed in 160 Puerto-Rican American drug users with Hepatitis C virus infection; 121 had chronic viremia (CV) and 39 were spontaneous clearance (SC). We further ruled out genetic stratification using short tandem repeats. Interaction between KIR gene receptor 2DL3/2DL3 and its ligand, C1/C1 of HLA-Cw alleles and spontaneous clearance was confirmed (p=0.03, OR=3.05). We also found a new interaction between the KIR receptor gene 2DL3 with HLA-DRB1*1201 (p=0.0001, OR=22) associated with SC, and an association of HLA DQB1*0501 (p=0.05, OR=0.30) with CV. Our findings suggested a role for MHC class II alleles in Hepatitis C virus peptide presentation to T cells together with NK ligand interaction involving pathways that will be useful for the development of immunotherapeutic interventions.
Mol Immunol 2008 May
PMID:Interaction of NK inhibitory receptor genes with HLA-C and MHC class II alleles in Hepatitis C virus infection outcome. 1828 78


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