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At least 721 records · Page 40Linked to original sources
PubMed2000

The cost of integrating hepatitis B virus vaccine into national immunization programmes: a case study from Addis Ababa.

National programmes of hepatitis B virus (HBV) vaccination are recommended by the World Health Organization for all countries. Countries suffering the highest burden of HBV disease are those most needy of universal vaccination, but are frequently of very low income and resources for health care are scarce. The introduction of HBV vaccination would inevitably stretch these resources further even with support of donor agencies. Thus an assessment of the cost-effectiveness of HBV vaccination is desirable to assist in decision making about resource allocation. We describe here a method for estimating the additional costs of introducing HBV vaccination into the Expanded Programme on Immunization (EPI) at a national level. Of fundamental importance is that this method enables costs to be assessed prior to the introduction of vaccination. We illustrate the method using a study carried out at the sub-national level, in the city of Addis Ababa, Ethiopia, but which can be expanded countrywide. The method, in brief, involved the use of a number of questionnaires which could be used to estimate the costs associated with the EPI programme from a large sample of the static clinics as well as from central sources. Since unit costs were collected along with the quantities of resources used and estimates of the capacity used for certain facilities (such as refrigerators), the additional cost of introducing HBV vaccine could be estimated largely by extrapolation of the resources used in vaccinating against diphtheria/pertussis/tetanus vaccine (which, similar to HBV vaccine, requires three doses). The estimation of costs is only part of the information required to make decisions on resource allocation, and should be used in association with measures of the burden of disease due to the infection in the community and effectiveness of the control programme at reducing this burden. The prediction of the latter, based upon a sound epidemiological understanding of the infection, is the subject of a forthcoming paper.

Cost Allocation↗
PubMed1990

Karyotypic instability and viral integration in polyoma virus-induced mouse salivary gland tumors.

Stable integration of polyoma viral DNA into the host-cell genome is a prerequisite for continuous expression of the transformed phenotype. In this study we have mapped the chromosomal location of integrated viral DNA sequences in a polyoma-induced mouse salivary gland adenocarcinoma. By in situ hybridization, a major integration site was assigned to chromosome 14, band B. The combined results from in situ hybridizations to metaphase chromosomes, primary tumors, and cultured tumor cells indicate the presence of both integrated and free polyoma viral DNA in the tumors. Cytogenetically, the tumors were characterized by a pronounced karyotypic instability. No abnormal cells with the same karyotype were observed in any of the tumors. Nevertheless, it was possible to recognize a preferential pattern of chromosomes variation with certain common recurrent and sporadic deviations. Clonal gains and/or losses of single chromosomes were seen in all tumors. It is concluded from these results that karyotypic instability may play an important role in the genesis and progression of polyoma virus-induced salivary gland tumors.

Adenocarcinoma↗
PubMed1992

Concerted integration of viral DNA termini by purified avian myeloblastosis virus integrase.

Concerted integration of retroviral DNA termini, which produces a characteristic duplication of sequences at the integration site and formation of the proviral state, is a necessary step of the retroviral life cycle. We investigated the pairwise integration reaction catalyzed by purified avian retrovirus integrase by measuring the response to solution parameters and how the sequences of the viral termini, which comprise the avian imperfect inverted repeat, affect the reaction. When we optimized the reaction, an efficiency was achieved which approached that measured in systems using cytoplasmic extracts from virus-infected cells. The response of purified avian integrase to solution parameters was similar to that of the integration activity derived from cellular extracts. For strand transfer, the U3 viral terminal sequences were preferred to those of the U5 termini, a result we previously showed for the trimming reaction. That the sequence preference was the same for trimming and strand transfer may be further evidence that only one catalytic site is used for both reactions. A significant number of integration sites were sequenced. Interesting trends were found for the fidelity of the host duplications to the avian 6-bp duplication size, the clustering of the integration sites in the nonessential region of the lambda host DNA, and the sequence characteristics of the duplication sites.

Avian Myeloblastosis Virus↗
PubMed2000

DNA sequence motifs which direct adeno-associated virus site-specific integration in a model system.

The DNA sequence motifs which direct adeno-associated virus type 2 site-specific integration are being investigated using a shuttle vector, propagated as a stable episome in cultured cell lines, as the target for integration. Previously, we reported that the minimum episomal targeting elements comprise a 16-bp binding motif (Rep binding site [RBS]) for a viral regulatory protein (Rep) separated by a short DNA spacer from a sequence (terminal resolution site [TRS]) that can serve as a substrate for Rep-mediated nicking activity (R. M. Linden, P. Ward, C. Giraud, E. Winocour, and K. I. Berns, Proc. Natl. Acad. Sci. USA 93:11288-11294, 1996; R. M. Linden, E. Winocour, and K. I. Berns, Proc. Natl. Acad. Sci. USA 93:7966-7972, 1996). We now report that episomal integration depends upon both the sequence and the position of the spacer DNA separating the RBS and TRS motifs. The spacer thus constitutes a third element required for site-specific episomal integration.

Binding Sites↗
PubMed2003

Cofactors for human immunodeficiency virus type 1 cDNA integration in vitro.

We have investigated the function of two DNA binding proteins that stimulate human immunodeficiency virus type 1 cDNA integration in vitro, the cellular HMGa1 protein and the viral nucleocapsid (NC) protein. Of the three forms of NC (NCp7, NCp9, and NCp15), we find that NCp9 is the most effective at increasing integration in vitro; thus, processing of NC may potentially modulate its activities during infection. We also found that maximal stimulation by NCp9 required roughly enough NC to coat the reactant DNAs whereas less HMGa1 was required, and the reactions displayed different optima for divalent metal cofactors and order of addition. These findings reveal probable distinct mechanisms of action in vitro.

Base Sequence↗
PubMed2005

Poly(ADP-ribose)polymerase-1 is required for integration of the human immunodeficiency virus type 1 genome near centromeric alphoid DNA in human and murine cells.

This study examined the efficiency of human immunodeficiency virus type 1 (HIV-1) integration in poly(ADP-ribose)polymerase-1 (PARP-1)-deficient murine cells and in human cell lines transfected with small interfering RNA against PARP-1 (PARP-1 siRNA). To semi-quantify the amount of integrated HIV-1 genome, real-time nested PCR was carried out using primers specific for Alu and alphoid DNA combined with primers for the HIV-1 genome. The results showed that the integration efficiency of the HIV-1 genome near Alu DNA, which is randomly distributed in the chromosome, is reduced in PARP-1-deficient murine cells, but not in PARP-1 siRNA-transfected human cells. By contrast, the integration efficiency of the HIV-1 genome near alphoid DNA, which is localized in the centromere region, is significantly reduced in PARP-1-deficient murine cells and in PARP-1 siRNA-transfected human cells. These results suggest that PARP-1 is required for HIV-1 integration near the centromere region both in human and murine cells.

Animals↗
PubMed1991

Integration of woodchuck hepatitis virus (WHV) DNA at two chromosomal sites (Vk and gag-like) in a hepatocellular carcinoma.

Integration of woodchuck hepatitis virus (WHV) DNA into the liver DNA of a woodchuck infected by the virus was investigated. Clonal viral integration was not detected three months before the appearance of four hepatocellular carcinomas (HCC). Integration of the viral DNA was detected in all four HCCs, of which one was chosen to determine the structure of the viral integration completely in a single tumor. The integration occurred in two sites. One part contains the viral DNA from the middle of the gene encoding surface antigen to two-thirds of the way through the gene encoding X protein (X) with no structural changes. The coding frame of the truncated X gene continues into the chromosomal sequence to make a possible fusion protein. The integration seems to have occurred by recombination within two direct repeats of the viral genome in one junction and by homologous recombination between viral DNA and chromosomal DNA in the other junction. The viral DNA is integrated into a spacer of the immunoglobulin L-chain Vk (IgVk) region without any chromosomal rearrangement accompanying the integration. The viral DNA at the second site has a complex structural rearrangement: part of the preS gene is duplicated and attached to the terminus of the gene encoding core antigen in a head-to-tail fashion, followed by three small fragments derived from other parts of the viral DNA. The integrated preS gene has its own 5' regulatory element and a coding frame consisting of the truncated preS gene, the other parts of viral DNA and the chromosomal sequence.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗
PubMed2000

Adeno-associated virus site-specifically integrates into a muscle-specific DNA region.

The nonpathogenic human virus adeno-associated virus type 2 (AAV) has evolved the potentially unique strategy to establish latency by site-specifically integrating its genome into human chromosome 19 (19q13.3-qter) at a locus designated AAVS1. This nonhomologous, site-specific recombination of viral DNA with the human genome provides a basis for developing targeted gene therapy vectors. To assess whether the region surrounding AAVS1 might have contributed to the selection of the specific integration site, we have investigated this locus. Here, we show that AAVS1 is closely linked to the slow skeletal troponin T gene, TNNT1, which has been mapped previously to 19q13.4. In support of this idea, we demonstrate that site-specific AAV DNA integration can result in the formation of TNNT1-AAV junctions. The question now arises whether muscle represents a natural target tissue for latent AAV infection. This possibility is of additional interest in view of recent observations that muscle tissue is particularly well suited for AAV-mediated gene transfer. The question also occurs whether latent infection by AAV can lead to phenotypic changes of the multinucleated muscle fiber cells.

Base Sequence↗
PubMed2005

Host factors regulating post-integration latency of HIV.

A recent study has provided important clues towards the identity of the host genes that conspire to promote post-integration latency of human immunodeficiency virus (HIV). Various genes controlling transcription, histone deacetylation and proteasome-mediated protein degradation have emerged as potential players. If the desired, but difficult, goal of complete virus eradication in HIV-infected patients is ever to be realized, the latent reservoir of HIV proviruses must be cleared. Understanding the molecular basis for viral latency is the key first step.

CD4-Positive T-Lymphocytes↗
PubMed1986

Integration of hepatitis B virus DNA in chromosome-specific satellite sequences.

We previously reported the cloning and detailed analysis of the integrated hepatitis B virus sequences in a human hepatoma cell line. We report here the integration of at least one of hepatitis B virus at human satellite DNA sequences. The majority of the cellular sequences identified by this satellite DNA were organized as a multimeric composition of a 0.6-kilobase EcoRI fragment. This clone hybridized in situ almost exclusively to the centromeric heterochromatin of chromosomes 1 and 16 and to a lower extent to chromosome 2 and to the heterochromatic region of the Y chromosome. The immediate flanking host sequence appeared as a hierarchy of repeating units which were almost identical to a previously reported human satellite III DNA sequence.

Carcinoma, Hepatocellular↗
PubMed1976

Evidence for tandem integration of avian myeloblastosis virus DNA with endogenous provirus in leukemic chicken cells.

The integration site of avian myeloblastosis virus (AMV) proviral DNA in DNA from leukemia chicken myeloblasts has been studied by three sequential nucleic acid hybridizations that can localize the proviral DNA according to the repetitiveness of the adjacent cellular DNA regions. First, large denatured cellular DNA fragments (2.1 x 10(6) daltons) were reassociated and fractionated according to sequence reiteration frequenct. Next, DNA remaining single-stranded in each fraction was immobilized on nitrocellulose filters hybridized with an excess of unlabeled 70S RNA from Rous-associated virus-0 to saturate the endogenous proviral DNA sequences.

Animals↗
PubMed1996

Unusual activation of the integrated preS1 promoter of woodchuck hepatitis virus in a liver tumour.

We have analysed abnormal virus RNAs produced from integrated woodchuck hepatitis virus (WHV) sequences in two woodchuck liver tumours. Analysis of cDNA clones revealed that these transcripts consisted of rearranged, virus-specific RNAs encoding the WHV surface antigens. In one tumour, transcription was driven by the major preS2/S promoter and terminated at a cryptic poly(A) signal in the 5' end of the P gene, giving rise to a truncated version of the normal viral S message. In contrast, the integrated preS2/S promoter remained silent in the second tumour. The start sites of two abundant WHV transcripts encoding the large and middle surface proteins were localized about 100 bp upstream and 300 bp downstream of the preS1 translation initiation codon, corresponding to minor start sites of the normal surface protein mRNAs in chronically infected liver. Thus, the preS1 promoter, a weak promoter in episomal replicative forms of the virus, was activated in the integrated state in this tumour. Our results indicate that alternative usage of the preS1 or the preS2/S promoter in the integrated state may yield differential production of the three virus surface proteins in woodchuck liver tumours.

Animals↗