NDLI: Enhancer-mediated role for polyomavirus middle T/small T in DNA replication.

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Characterization of nef sequences in long-term survivors of human immunodeficiency virus type 1 infection.

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Immortalization of human B lymphocytes by a plasmid containing 71 kilobase pairs of Epstein-Barr virus DNA.

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Genetic diversity of the envelope glycoprotein from human immunodeficiency virus type 1 isolates of African origin.

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Enhancer-mediated role for polyomavirus middle T/small T in DNA replication.

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Effect of different donor cells on human immunodeficiency virus type 1 replication and selection in vitro.

Viral RNA modulates the acid sensitivity of foot-and-mouth disease virus capsids.

Hyperphosphorylation of mutant influenza virus matrix protein, M1, causes its retention in the nucleus.

Long terminal repeat enhancer core sequences in proviruses adjacent to c-myc in T-cell lymphomas induced by a murine retrovirus.

Characterization of recombinant murine leukemia virus integrase.

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Human immunodeficiency virus Tat induces functional unresponsiveness in T cells.

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Resistance to nucleoside analogs of selective mutants of human immunodeficiency virus type 2 reverse transcriptase.

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Isolation of a monoclonal antibody which blocks vaccinia virus infection.

Equal levels of gp120 retention and neutralization resistance of phenotypically distinct primary human immunodeficiency virus type 1 variants upon soluble CD4 treatment.

Human immunodeficiency virus type 1 Nef induces accumulation of CD4 in early endosomes.

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Major histocompatibility complex class I-restricted cytotoxic T-lymphocyte responses in horses infected with equine herpesvirus 1.

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Direct interactions between autoantigen La and human immunodeficiency virusleader RNA.

Identification of multirestricted immunodominant regions recognized by cytolytic T lymphocytes in the human immunodeficiency virus type 1 Nef protein.

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Enhancer-mediated role for polyomavirus middle T/small T in DNA replication.

Content Provider	PubMed Central
Author	Chen, M. C. Redenius, D. Osati-ashtiani, F. Fluck, M. M.
Abstract	A major role for polyomavirus middle T/small T antigens in viral DNA synthesis was uncovered by examining the replication of middle T/small T-deficient mutants (hr-t mutants). hr-t mutants in the A2 genetic background showed a 16- to 100-fold defect in genome accumulation relative to the wild type when infections were carried out in exponentially growing NIH 3T3 cells in medium supplemented with low levels of serum (< 2.0%). A proportional decrease in the level of viral early transcripts was also seen. The replication defect of the hr-t mutants was partially overcome in the presence of the phorbol ester 12-O-tetradecanoylphorbol-13-acetate. The defect was also alleviated by a duplication encompassing the alpha core enhancer domain that contains binding sites for the transcriptional activators PEA1/AP-1 and PEA3/c-ets. Such a duplication is present in all naturally occurring hr-t mutants and absent in the A2 strain. The effects of 12-O-tetradecanoylphorbol-13-acetate and alpha core duplication were additive but did not fully complement the absence of middle T/small T. In mixed infection competition experiments with two hr-t mutants, a genome that carried an alpha core duplication had a replication advantage (up to 17-fold) over a genome without duplication. This result demonstrates that one effect of the duplication is exerted directly at the level of DNA replication. The advantage of the duplication-bearing genome was established during the earliest stages of replication and was not further amplified in later rounds of replication. In the presence of middle T/small T, both genomes replicated to high levels and the advantage of the duplication-bearing genome was eliminated. On the basis of these results, we propose that factors that bind the alpha core domain (presumably PEA1 and PEA3) are present in limiting amounts in exponentially growing NIH 3T3 cells and play a crucial role in polyomavirus DNA replication. We further suggest that middle T and/or small T stimulates viral DNA replication by activating these factors. The fact that all middle T-/small T-defective hr-t mutants have evolved to contain enhancer duplications that encompass the PEA1 and PEA3 binding sites in the alpha core domain and partially restore their replication defect (A. Amalfitano, M. C. Chen, and M. Fluck, unpublished data) provides an adequate explanation for the fact that the importance of the role of the middle T and/or small T function in DNA replication has not been recognized previously. Much evidence is available in support of separate elements of this model.(ABSTRACT TRUNCATED AT 400 WORDS)
Starting Page	326
File Format	PDF
ISSN	10985514
e-ISSN	10985514
Journal	Journal of Virology
Issue Number	1
Volume Number	69
Language	English
Publisher Date	1995-01-01
Access Restriction	Open
Subject Keyword	Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Virology Immunology Microbiology Insect Science

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