Publications
343 results found
Kellam P, Albà MM, 2002, Virus bioinformatics: databases and recent applications., Appl Bioinformatics, Vol: 1, Pages: 37-42, ISSN: 1175-5636
Bioinformatics is now used as an umbrella term for almost all aspects of computational biology. Bioinformatics research will have an impact on all of biology, and virology is not immune from these research methods. Although virology has been slower to embrace bioinformatics this is now changing, particularly in the areas of viral sequences databasing and the systematic identification of viral and host homologous proteins. Here we will review some of these recent advances focusing mainly on the herpesvirus.
Kellam P, 2001, Post-genomic virology: the impact of bioinformatics, microarrays and proteomics on investigating host and pathogen interactions, REVIEWS IN MEDICAL VIROLOGY, Vol: 11, Pages: 313-329, ISSN: 1052-9276
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- Citations: 26
Kellam P, 2001, Microarray gene expression database: progress towards an international repository of gene expression data., Microarray Gene Expression Database group meeting (MGED3), Publisher: BioMed Central, ISSN: 1474-7596
A report on the third Microarray Gene Expression Databasegroup meeting (MGED3), Stanford University, Palo Alto,California, USA, 29-31 March, 2001.
Kellam P, Liu X, Martin N, et al., 2001, A framework for modelling short, high-dimensional multivariate time series: Preliminary results in virus gene expression data analysis, Pages: 218-227, ISSN: 0302-9743
Short, high-dimensionalMultivariateTime Series (MTS) data are common in many fields such as medicine, finance and science, and any advance in modelling this kind of data would be beneficial. Nowhere is this more true than functional genomics where effective ways of analyzing gene expression data are urgently needed. Progress in this area could help obtain a “global” view of biological processes, and ultimately lead to a great improvement in the quality of human life. We present a computational framework for modelling this type of data, and report preliminary experimental results of applying this framework to the analysis of gene expression data in the virology domain. The framework contains a threestep modelling strategy: correlation search, variable grouping, and short MTS modelling. Novel research is involved in each step which has been individually tested on different real-world datasets in engineering and medicine. This is the first attempt to integrate all these components into a coherent computational framework, and test the framework on a very challenging application area, which has produced promising results.
Radkov SA, Kellam P, Boshoff C, 2001, Use of an apparatus for automatic lung straightening in postoperative treatment of the pleural cavity, Biomedical Engineering, Vol: 35, Pages: 323-325, ISSN: 0006-3398
Albà MM, Lee D, Pearl FMG, et al., 2001, VIDA:: a virus database system for the organization of animal virus genome open reading frames, NUCLEIC ACIDS RESEARCH, Vol: 29, Pages: 133-136, ISSN: 0305-1048
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- Citations: 31
Jenner RG, Albà MM, Boshoff C, et al., 2001, Kaposi's sarcoma-associated herpesvirus latent and lytic gene expression as revealed by DNA arrays, JOURNAL OF VIROLOGY, Vol: 75, Pages: 891-902, ISSN: 0022-538X
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- Citations: 290
Albà MM, Das RJ, Orengo CA, et al., 2001, Genomewide function conservation and phylogeny in the herpesviridae, GENOME RESEARCH, Vol: 11, Pages: 43-54, ISSN: 1088-9051
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- Citations: 53
Kellam P, 2000, Host-pathogen studies in the post-genomic era, Genome Biology, Vol: 1, ISSN: 1465-6906
Several studies are starting to show the power of DNA microarrays to identify interactions between animal hosts and their pathogens, and have revealed interesting correlations between host responses to different infectious agents. © GenomeBiology.com.
Radkov SA, Kellam P, Boshoff C, 2000, The latent nuclear antigen of Kaposi sarcoma-associated herpesvirus targets the retinoblastoma-E2F pathway and with the oncogene <i>Hras</i> transforms primary rat cells, NATURE MEDICINE, Vol: 6, Pages: 1121-1127, ISSN: 1078-8956
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- Citations: 391
Kellam P, 2000, Host-pathogen studies in the post-genomic era., Genome Biology, Vol: 1, ISSN: 1474-7596
Several studies are starting to show the power of DNA microarrays to identify interactions between animal hosts and their pathogens, and have revealed interesting correlations between host responses to different infectious agents.
Dupin N, Diss TL, Kellam P, et al., 2000, HHV-8 is associated with a plasmablastic variant of Castleman disease that is linked to HHV-8-positive plasmablastic lymphoma, BLOOD, Vol: 95, Pages: 1406-1412, ISSN: 0006-4971
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- Citations: 477
Kellam P, Bourboulia D, Dupin N, et al., 1999, Characterization of monoclonal antibodies raised against the latent nuclear antigen of human herpesvirus 8, Journal of Virology, Vol: 73, Pages: 5149-5155, ISSN: 0022-538X
Human herpesvirus 8 (HHV-8; also designated Kaposi’s sarcoma-associated herpesvirus) is the likely etiological agent of Kaposi’s sarcoma (KS). HHV-8 encodes a latent nuclear antigen (LNA) which is the product of the viral gene orf 73. LNA is recognized by most infected patient sera and is the basis of current immunofluorescence assays used in epidemiological studies of HHV-8 infection. Here we describe the characterization of four monoclonal antibodies raised to the C-terminal third of LNA–glutathioneS-transferase fusion proteins. These monoclonal antibodies recognized discrete linear epitopes within the C terminus and repetitive region of LNA, detected antigen in primary effusion lymphoma (PEL) cells, and precipitated a 220- to 230-kDa protein doublet corresponding to LNA from HHV-8-infected PEL cell lines. In situ immunocytochemistry of KS lesions with these antibodies show that LNA is extensively expressed in KS spindle cells.
Talbot SJ, Weiss RA, Kellam P, et al., 1999, Transcriptional analysis of human herpesvirus-8 open reading frames 71, 72, 73, K14, and 74 in a primary effusion lymphoma cell line, VIROLOGY, Vol: 257, Pages: 84-94, ISSN: 0042-6822
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- Citations: 134
Dupin N, Fisher C, Kellam P, et al., 1999, Distribution of human herpesvirus-8 latently infected cells in Kaposi's sarcoma, multicentric Castleman's disease, and primary effusion lymphoma, PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, Vol: 96, Pages: 4546-4551, ISSN: 0027-8424
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- Citations: 553
Thomas MC, Ballantine SP, Bethell SS, et al., 1998, Single amino acid substitutions disrupt tetramer formation in the dihydroneopterin aldolase enzyme of <i>Pneumocystis carinii</i>, BIOCHEMISTRY, Vol: 37, Pages: 11629-11636, ISSN: 0006-2960
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- Citations: 11
Kellam P, 1998, Molecular identification of novel viruses, TRENDS IN MICROBIOLOGY, Vol: 6, Pages: 160-166, ISSN: 0966-842X
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- Citations: 14
Weiss RA, Whitby D, Talbot S, et al., 1998, Human herpesvirus type 8 and Kaposi's sarcoma., J Natl Cancer Inst Monogr, Pages: 51-54, ISSN: 1052-6773
Kaposi's sarcoma-associated herpesvirus or human herpesvirus type 8 (HHV-8) is present in all forms of Kaposi's sarcoma (KS) as well as in primary effusion lymphomas and some cases of Castleman's disease. In KS tissues, HHV-8 is present in endothelial and spindle cells. Current serologic tests suggest that HHV-8 is predominantly found in those at risk of KS and is not as widespread as most other human herpesviruses. HHV-8 encodes various proteins that may play a role in promotion of cellular growth, including cyclin- and G-coupled protein receptor homologues, and anti-apoptotic proteins, including Bcl-2, IL-6 (i.e., interleukin 6), and FLIP (i.e., FLICE inhibitory protein) homologues. In addition, HHV-8 encodes two macrophage inflammatory-like proteins with anti-human immunodeficiency virus and angiogenic potential.
Thomas MC, Ballantine SP, Kellam P, et al., 1997, Molecular study of the enzymes involved in the folate biosynthesis pathway, alternative targets for drugs, Ars Pharmaceutica, Vol: 38, Pages: 129-135, ISSN: 0004-2927
Folate derivates are essential co-factors in the biosynthesis of purines, pyrimidines and certain amino acids in living cells. Most microbial cells must synthesise folates de novo since they lack the carrier-mediated active transport system of mammalian cells which allows the use of preformed dietary folates. The de novo synthesis of dihydrofolate from GTP requires the participation of several enzyme activities that are unique to microbial cells. The enzymes of the folic acid biosynthesis pathway represent, therefore, ideal targets for antimicrobial chemotherapy since they have no mammalian counter-parts, and high level selectivity should be achievable. Indeed, dihydropteroate synthase which catalyses the condensation of p- aminobenzoic acid and 6-hydroxi-methil-7,8-dihydropterin pyrophosphate to form dihydropteroate, is the target of sulfa drugs. The molecualr characterization of individual enzyme activities, domain folding and domain interactions within the polypeptide, should aid the design of novel antimicrobial agents.
Weiss RA, Kellam P, 1997, Virology - Illicit viral DNA, NATURE, Vol: 390, Pages: 235-236, ISSN: 0028-0836
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- Citations: 15
Kellam P, Boshoff C, Whitby D, et al., 1997, Identification of a major latent nuclear antigen, LNA-1, in the human herpesvirus 8 genome., J Hum Virol, Vol: 1, Pages: 19-29, ISSN: 1090-9508
OBJECTIVES: Human herpesvirus 8 (HHV-8) is strongly associated with all forms of Kaposi's sarcoma (KS) and with primary effusion lymphomas (PEL). KS patients' sera are immunoreactive against discrete nuclear localizing antigens in PEL cell lines. This study sought to identify and characterize these nuclear localizing proteins. STUDY DESIGN/METHODS: KS patients' sera were used to screen a cDNA expression library derived from a PEL cell line (BCP-1) latently infected with HHV-8. RESULTS: An HHV-8-specific cDNA clone was isolated. It encoded one partial and two complete open reading frames (ORFs): ORF 73, ORF 72 (v-cyclin), and K13, respectively. The immunodominant epitope was mapped to the C-terminal domain of ORF 73. Analysis with the KS patients' sera of HEK 293 cells transfected with a clone encompassing the complete coding region of ORF 73, ORF 72, and K13 gave a nuclear immunofluorescence pattern similar to that observed in BCP-1 cells. Western blot analysis with KS patients' sera of transfected HEK 293 cells revealed an immunoreactive protein of 220 to 230 kD that was similar to that observed previously in PEL cell lines. After induction of lytic replication of HHV-8 in BCP-1 cells with n-butyrate, we observed a major reduction in the expression of an ORF 73-specific 6.6-kb mRNA, indicating that this region is under latent control. CONCLUSIONS: These data identify a region of HHV-8 encoding for a major immunoreactive latent nuclear antigen (LNA-1), analogous to the Epstein-Barr virus latent nuclear antigens.
KELLAM P, DALLAS WS, BALLANTINE SP, et al., 1995, Functional cloning of the dihydropteroate synthase gene of Staphylococcus haemolyticus, FEMS Microbiology Letters, Vol: 134, Pages: 165-169, ISSN: 0378-1097
A 1.7-kilobase fragment of the Staphylococcus haemolyticus chromosome containing the dihydropteroate synthase gene has been cloned by complementation in a temperature-sensitive mutant of Escherichia coli. The gene, designated folP, predicts a gene product of 29613 Da which shares significant amino acid sequence identity with other known bacterial dihydropteroate synthases. Analysis of the DNA sequence upstream and downstream of folP identified two further, incomplete open reading frames, one of which shows predicted amino acid sequence similarity to a second bacterial folic acid synthesis enzyme, dihydroneopterin aldolase.
Kellam P, 1995, Functional cloning of the dihydropteroate synthase gene of Staphylococcus haemolyticus, FEMS Microbiology Letters, Vol: 134, Pages: 165-169, ISSN: 0378-1097
KELLAM P, LARDER BA, 1995, Retroviral recombination can lead to linkage of reverse-transcriptase mutations that confer increased zidovudine resistance, Journal of Virology, Vol: 69, Pages: 669-674, ISSN: 0022-538X
Genetic recombination between viral genomes has been shown to contribute to the generation of genetic diversity during retrovirus infections. The role of recombination in the development of human immunodeficiency virus type 1 (HIV-1) zidovudine resistance was investigated as a possible cause of the formation of the linked Leu-41/Tyr-215 resistance genotype. Zidovudine resistance is conferred by the presence of subsets of four or five amino acid substitutions in the HIV-1 reverse transcriptase. Zidovudine therapy of asymptomatic HIV-1-infected individuals results in the selection of drug-resistant variants that posses defined combinations of the five zidovudine resistance mutations. The linked Leu-41/Tyr-215 resistance genotype appears central to the continued development of high-level zidovudine resistance. By using genetically tagged mutant viruses, it was possible readily to select recombinant viruses from mixed infections of Leu-41 and Tyr-215 single mutants in the presence of zidovudine drup pressure. After three passages of a mixed infection in the presence of drug, 38% of clones screened were recombinant double mutants. In the absence of zidovudine selection, little change in the mixed virus populations was noted. No evidence of de novo generation of mutations at codons 41 and 215 was seen during any in vitro passage. This provides the first example of the role of retroviral recombination in the development of HIV-1 variants with increased drug resistance.
KELLAM P, BOUCHER CAB, TIJNAGEL J, et al., 1994, ZIDOVUDINE TREATMENT RESULTS IN THE SELECTION OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 VARIANTS WHOSE GENOTYPES CONFER INCREASING LEVELS OF DRUG-RESISTANCE, JOURNAL OF GENERAL VIROLOGY, Vol: 75, Pages: 341-351, ISSN: 0022-1317
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- Citations: 96
KELLAM P, LARDER BA, 1994, RECOMBINANT VIRUS ASSAY - A RAPID, PHENOTYPIC ASSAY FOR ASSESSMENT OF DRUG SUSCEPTIBILITY OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 ISOLATES, ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, Vol: 38, Pages: 23-30, ISSN: 0066-4804
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- Citations: 175
LARDER BA, KOHLI A, KELLAM P, et al., 1993, QUANTITATIVE DETECTION OF HIV-1 DRUG-RESISTANCE MUTATIONS BY AUTOMATED DNA-SEQUENCING, NATURE, Vol: 365, Pages: 671-673, ISSN: 0028-0836
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- Citations: 171
LARDER BA, KELLAM P, KEMP SD, 1993, CONVERGENT COMBINATION THERAPY CAN SELECT VIABLE MULTIDRUG-RESISTANT HIV-1 IN-VITRO, NATURE, Vol: 365, Pages: 451-453, ISSN: 0028-0836
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- Citations: 145
BOUCHER CAB, VANLEEUWEN R, KELLAM P, et al., 1993, EFFECTS OF DISCONTINUATION OF ZIDOVUDINE TREATMENT ON ZIDOVUDINE SENSITIVITY OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 ISOLATES, ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, Vol: 37, Pages: 1525-1530, ISSN: 0066-4804
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- Citations: 54
BOUCHER CAB, LANGE JMA, MIEDEMA FF, et al., 1992, HIV-1 BIOLOGICAL PHENOTYPE AND THE DEVELOPMENT OF ZIDOVUDINE RESISTANCE IN RELATION TO DISEASE PROGRESSION IN ASYMPTOMATIC INDIVIDUALS DURING TREATMENT, AIDS, Vol: 6, Pages: 1259-1264, ISSN: 0269-9370
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- Citations: 127
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