Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.7.7.7 (DNA polymerase)
 17,007 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have been studying the role of human cytomegalovirus (HCMV) as a potential cofactor in human immunodeficiency virus (HIV)-related disease. The clinical relevance of HCMV is highlighted by the fact that it is a principal viral pathogen in patients with AIDS and is known to infect the same cells as HIV. In this study, we focused on the molecular interactions between HIV and HCMV in human fibroblasts and in the human glioblastoma/astrocytoma-derived cell line U373 MG, cells which can be productively infected by both viruses. Because these cells are CD4-, we used HIV pseudotyped with a murine amphotropic retrovirus as described previously (D. H. Spector, E. Wade, D. A. Wright, V. Koval, C. Clark, D. Jaquish, and S. A. Spector, J. Virol. 64:2298-2308, 1990). Initial studies showed that when cells were preinfected with HIV (Ampho-1B) for 5 days and then superinfected with HCMV, HIV antigen production dropped significantly in the coinfected cells but continued to rise in cells infected with HIV (Ampho-1B) alone. HCMV production, however, was unaffected by the presence of HIV. Further analysis showed that HIV steady-state RNA levels and gag and env protein production were also inhibited in the presence of HCMV. The transcriptional inhibition of HIV was particularly surprising in view of the previous results of several other laboratories as well as our own that HCMV infection stimulates HIV long terminal repeat-chloramphenicol acetyltransferase (LTR-CAT) expression in transient expression assays. To investigate this further, we transfected the HIV LTR-CAT construct into either uninfected cells or cells which had been preinfected with HIV. The cells were infected with HCMV 24 h posttransfection and assayed for CAT gene expression at 48 h after HCMV infection. Although there was some stimulation of the LTR-CAT in cells that were dually infected by HIV and HCMV, it was 16-fold less than that in the cells infected only with HCMV. This suggests that in the presence of the HIV infection, the stimulation of the HIV LTR-CAT gene by HCMV is significantly reduced. Experiments with UV-irradiated HCMV and the HCMV DNA polymerase inhibitor ganciclovir showed that HCMV transcription is necessary for the reduction in HIV production to occur; however, replication of the HCMV genome or any events which take place after DNA replication are not necessary. These results, coupled with the observation that inhibition is usually first seen between 8 and 24 h after HCMV infection, suggest that an HCMV early protein is involved in repression of HIV.
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PMID:Human cytomegalovirus inhibits human immunodeficiency virus replication in cells productively infected by both viruses. 165 86

The sites of recombination between the transforming gene of avian myeloblastosis virus (AMV) and its natural helper myeloblastosis-associated virus (MAV) have been determined. In AMV, the cellular sequence substituting for the viral envelope (env) gene gives rise to a different carboxyl terminus of the DNA polymerase. The 5'-recombination site coincides with the RNA splice acceptor site for the production of env mRNA in MAV-infected cells. The 3'-recombination site reveals that the last 11 amino acids including the termination codon are shared by the env protein and AMV transforming protein. The RNA splice acceptor site for the generation of subgenomic v-myb mRNA is located 84 nucleotides downstream from the 5'-recombination site. The AMV transforming protein consists of helper virus-related sequences at both of its amino and carboxyl termini, and all but 84 nucleotides of the cell-derived v-myb sequence. The comparison of MAV gp85 amino acid sequence with those of subgroups B, C, and E indicates that the MAV present in clone lambda 10A2-1 belongs to subgroup B. The high degree of homology among different avian retroviruses of the same subgroup indicates that the amino acid sequence of gp85 is important in determining the conformation of the envelope glycoprotein.
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PMID:Sites of recombination between the transforming gene of avian myeloblastosis virus and its helper virus. 299 54

The analysis of retroviral mutants has played a critical role in the development of our understanding of the complex viral life cycle. The most fundamental result of that analysis has been the definition of the replication functions encoded by the viruses. From a biochemical examination of a particular step in the life cycle it is difficult to determine, for example, whether that step is catalyzed by a viral or a host enzyme; but the isolation of a viral mutant defective in that step can firmly establish that a viral function is involved. In this way many facts about the viruses have been established. We know that reverse transcriptase is encoded by the virus; that RNAase H and DNA polymerase activities reside on the same gene product; that processing of many precursor proteins is mediated by a viral proteinase; and that establishment of the integrated provirus requires a viral protein. The list of functions mediated by viral enzymes has largely been defined by the mutants isolated and studied in various laboratories. The second significant result of the studies of viral mutants has been the assignation of the replication functions to particular viral genes, and then more specifically to particular domains of these genes. Mutants and viral variants have been essential in the determination, for example, that the gag protein is the critical gene product for the assembly of a virion particle; that the env protein is the determinant of species specificity of infection; or that the LTR is a major determinant of tissue tropism and leukemogenicity. The subdivisions of functions within a given gene have similarly hinged on mutants. Genetic mapping was needed to establish that P30 is the most important region for assembly; that the proteinase and integrase functions reside, respectively, in the 5' and 3' portions of the pol gene; and that the glycosylated gag protein is dispensable for replication. A third important area of knowledge has depended heavily on viral mutants: the determination of host functions and proteins that interact with viral proteins. Variant viruses with altered or restricted host ranges serve to define differences between pairs of different host cells, and the mapping of the viral mutations serves to define the viral protein important in that interaction with the host. These studies are only in their infancy, but it is clear that substantial efforts will be made to further analyze these host functions.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Mutants of murine leukemia viruses and retroviral replication. 303 30