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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
MeSH Review


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Disease relevance of Proviruses

  • Approximately 50% of tumors induced by mouse mammary tumor virus (MMTV) contain an acquired provirus within a limited region of chromosomal DNA, termed int-2 [1].
  • Two of these proviruses, Emv-16 and Emv-17, are tightly linked and segregate with the high viremia phenotype in backcrossed mice [2].
  • The present report describes the isolation of linear extrachromosomal copias whose structure closely resembles the analogous retrovirus provirus linears and whose synthesis is unaffected by inhibitors of the cellular DNA polymerase responsible for chromosomal DNA replication [3].
  • The hypothesis that c-myc may be involved in neoplastic transformation has been strengthened by the finding that B-cell lymphomas induced in chickens by avian leukosis virus (ALV) are often associated with increased expression of c-myc resulting from integration of the ALV provirus adjacent to the c-myc gene [4].
  • There is now good evidence that the induction of mammary carcinomas by mouse mammary tumour virus (MMTV) involves provirus activation of specific cellular genes [5].

High impact information on Proviruses

  • Because of their ability to stimulate very strong T cell responses in MHC-identical mice, minor lymphocyte stimulatory (Mls) antigens, discovered more than 20 years ago, are now known to be SAgs encoded by endogenous MMTV proviruses that have randomly integrated into germ cells [6].
  • Three quarters contained a provirus within the known pim-1 or pim-2 loci, new loci bmi-1 and emi-1, or combinations of these. bmi-1 insertions predominated, occurring in half the tumors, and resulted in elevated bmi-1 mRNA levels [7].
  • Using oligonucleotide probes specific for different classes of murine leukemia virus, we have identified and cloned a provirus present in HRS/J hr/hr animals but absent in HRS/J +/+ [8].
  • Five of 37 cell lines contained proviruses in a common viral integration site termed the ecotropic virus integration 1 site (Evi-1) [9].
  • Genetic analyses showed perfect concordance between the hr phenotype and the presence of the provirus in a number of inbred and congenic strains of mice [8].

Chemical compound and disease context of Proviruses

  • An ancient provirus has imposed androgen regulation on the adjacent mouse sex-limited protein gene [10].
  • Thus, expression of int-2 seems to be caused by an enhancing activity on the MMTV provirus which is not dependent on steroid hormone and is specific for mammary tumor cells with epithelial characteristics [11].
  • Stable acquisition of the ZN(Smu/S gamma 2b)tk1 vector was selected in G-418 and switch region recombination within these proviruses was selected by resistance to the drug bromodeoxyuridine (BUdR) [12].
  • The endogenous provirus in certain cell types termed chicken helper factor positive (chf+) can synthesize the envelope glycoprotein [13].
  • Thus the LTR-linked neo gene is expressed because the provirus is integrated in the vicinity of this enhancer that is active in undifferentiated EC cells [14].

Biological context of Proviruses


Anatomical context of Proviruses

  • These results suggest that p50 and Sp1 contribute to the establishment of the nucleosomal arrangement of the uninduced provirus in resting T cells, and that p65 activates transcription by recruitment of the RNA polymerase II transcriptional machinery to the chromatin-repressed basal promoter [20].
  • Analyses of the cellular and viral Kirsten ras genes (c-Ki-ras and v-Ki-ras, respectively) during malignant tumor progression were performed by using Kirsten murine sarcoma virus-transformed BALB/c 3T3 cells that harbor a replication-defective provirus [21].
  • In contrast to the simplified retroviral vector, hADA expression in these recipients was short lived (less than 8 weeks), despite the continued presence of intact provirus in DNA prepared from bone marrow of these mice [22].
  • Infection of mice with MMTV proviruses containing CDP binding site mutations elevated viral RNA levels in virgin mammary glands and shortened mammary tumor latency [23].
  • Sequences of the provirus not required for kinase activity appeared unnecessary for abrogating the fibroblast requirement for PDGF [24].

Gene context of Proviruses

  • RF/J mice carry three endogenous ecotropic murine leukemia proviruses designated Emv-1, Emv-16, and Emv-17 [2].
  • Furthermore, our data indicate that Notch1 alleles mutated by provirus insertion can lead to increased expression of truncated and full-length (330/280-kD) Notch1 proteins, both being produced in a cleaved and uncleaved form [25].
  • Mls-1-like superantigen in the MA/MyJ mouse is encoded by a new mammary tumor provirus that is distinct from Mtv-7 [26].
  • Interestingly, the superantigen activity of this mouse strain segregates with a new mammary tumor provirus, Mtv-43, not seen in other inbred strains [26].
  • The combination of HDAC inhibitors and Tat merits consideration as a new strategy for purging latent HIV proviruses from their cellular reservoirs [27].

Analytical, diagnostic and therapeutic context of Proviruses


  1. Tumorigenesis by mouse mammary tumor virus: proviral activation of a cellular gene in the common integration region int-2. Dickson, C., Smith, R., Brookes, S., Peters, G. Cell (1984) [Pubmed]
  2. High frequency germline acquisition of ecotropic MuLV proviruses in SWR/J-RF/J hybrid mice. Jenkins, N.A., Copeland, N.G. Cell (1985) [Pubmed]
  3. Role of reverse transcription in the generation of extrachromosomal copia mobile genetic elements. Flavell, A.J. Nature (1984) [Pubmed]
  4. Identification and nucleotide sequence of a human locus homologous to the v-myc oncogene of avian myelocytomatosis virus MC29. Colby, W.W., Chen, E.Y., Smith, D.H., Levinson, A.D. Nature (1983) [Pubmed]
  5. Activation of cellular gene by mouse mammary tumour virus may occur early in mammary tumour development. Peters, G., Lee, A.E., Dickson, C. Nature (1984) [Pubmed]
  6. Superantigens of mouse mammary tumor virus. Acha-Orbea, H., MacDonald, H.R. Annu. Rev. Immunol. (1995) [Pubmed]
  7. Novel zinc finger gene implicated as myc collaborator by retrovirally accelerated lymphomagenesis in E mu-myc transgenic mice. Haupt, Y., Alexander, W.S., Barri, G., Klinken, S.P., Adams, J.M. Cell (1991) [Pubmed]
  8. Role of endogenous retroviruses as mutagens: the hairless mutation of mice. Stoye, J.P., Fenner, S., Greenoak, G.E., Moran, C., Coffin, J.M. Cell (1988) [Pubmed]
  9. Retroviral activation of a novel gene encoding a zinc finger protein in IL-3-dependent myeloid leukemia cell lines. Morishita, K., Parker, D.S., Mucenski, M.L., Jenkins, N.A., Copeland, N.G., Ihle, J.N. Cell (1988) [Pubmed]
  10. An ancient provirus has imposed androgen regulation on the adjacent mouse sex-limited protein gene. Stavenhagen, J.B., Robins, D.M. Cell (1988) [Pubmed]
  11. Oncogene expression during progression of mouse mammary tumor cells; activity of a proviral enhancer and the resulting expression of int-2 is influenced by the state of differentiation. Sonnenberg, A., van Balen, P., Hilgers, J., Schuuring, E., Nusse, R. EMBO J. (1987) [Pubmed]
  12. Immunoglobulin heavy chain switch region recombination within a retroviral vector in murine pre-B cells. Ott, D.E., Alt, F.W., Marcu, K.B. EMBO J. (1987) [Pubmed]
  13. Independent regulation of endogenous and exogenous avian RNA tumor virus genes. Hayward, W.S., Hanafusa, H. Proc. Natl. Acad. Sci. U.S.A. (1976) [Pubmed]
  14. A cellular enhancer of retrovirus gene expression in embryonal carcinoma cells. Taketo, M., Tanaka, M. Proc. Natl. Acad. Sci. U.S.A. (1987) [Pubmed]
  15. Analysis of FBJ-MuSV provirus and c-fos (mouse) gene reveals that viral and cellular fos gene products have different carboxy termini. Van Beveren, C., van Straaten, F., Curran, T., Müller, R., Verma, I.M. Cell (1983) [Pubmed]
  16. Retroviruses and insertional mutagenesis in mice: proviral integration at the Mov 34 locus leads to early embryonic death. Soriano, P., Gridley, T., Jaenisch, R. Genes Dev. (1987) [Pubmed]
  17. Amplified env and gag products on AKR cells. Origin from different murine leukemia virus genomes. Tung, J.S., Fleissner, E. J. Exp. Med. (1980) [Pubmed]
  18. Analysis of thymic endogenous retroviral expression in murine lupus. Genetic and immune studies. Krieg, A.M., Steinberg, A.D. J. Clin. Invest. (1990) [Pubmed]
  19. Beta cell expression of endogenous xenotropic retrovirus distinguishes diabetes-susceptible NOD/Lt from resistant NON/Lt mice. Gaskins, H.R., Prochazka, M., Hamaguchi, K., Serreze, D.V., Leiter, E.H. J. Clin. Invest. (1992) [Pubmed]
  20. NF-kappa B-mediated chromatin reconfiguration and transcriptional activation of the HIV-1 enhancer in vitro. Pazin, M.J., Sheridan, P.L., Cannon, K., Cao, Z., Keck, J.G., Kadonaga, J.T., Jones, K.A. Genes Dev. (1996) [Pubmed]
  21. Amplification and rearrangement of the Kirsten ras oncogene in virus-transformed BALB/c 3T3 cells during malignant tumor progression. Radinsky, R., Kraemer, P.M., Raines, M.A., Kung, H.J., Culp, L.A. Proc. Natl. Acad. Sci. U.S.A. (1987) [Pubmed]
  22. Retroviral gene transfer of human adenosine deaminase in murine hematopoietic cells: effect of selectable marker sequences on long-term expression. Apperley, J.F., Luskey, B.D., Williams, D.A. Blood (1991) [Pubmed]
  23. The homeodomain protein CDP regulates mammary-specific gene transcription and tumorigenesis. Zhu, Q., Maitra, U., Johnston, D., Lozano, M., Dudley, J.P. Mol. Cell. Biol. (2004) [Pubmed]
  24. Abelson murine leukemia virus induces platelet-derived growth factor-independent fibroblast growth: correlation with kinase activity and dissociation from full morphologic transformation. Rees-Jones, R.W., Goldfarb, M., Goff, S.P. Mol. Cell. Biol. (1989) [Pubmed]
  25. Frequent provirus insertional mutagenesis of Notch1 in thymomas of MMTVD/myc transgenic mice suggests a collaboration of c-myc and Notch1 for oncogenesis. Girard, L., Hanna, Z., Beaulieu, N., Hoemann, C.D., Simard, C., Kozak, C.A., Jolicoeur, P. Genes Dev. (1996) [Pubmed]
  26. Mls-1-like superantigen in the MA/MyJ mouse is encoded by a new mammary tumor provirus that is distinct from Mtv-7. Rudy, C.K., Kraus, E., Palmer, E., Huber, B.T. J. Exp. Med. (1992) [Pubmed]
  27. NF-kappaB p50 promotes HIV latency through HDAC recruitment and repression of transcriptional initiation. Williams, S.A., Chen, L.F., Kwon, H., Ruiz-Jarabo, C.M., Verdin, E., Greene, W.C. EMBO J. (2006) [Pubmed]
  28. Deleted HTLV-I provirus in blood and cutaneous lesions of patients with mycosis fungoides. Hall, W.W., Liu, C.R., Schneewind, O., Takahashi, H., Kaplan, M.H., Röupe, G., Vahlne, A. Science (1991) [Pubmed]
  29. Genomic structure of HTLV (human T-cell leukemia virus): detection of defective genome and its amplification in MT-2 cells. Kobayashi, N., Konishi, H., Sabe, H., Shigesada, K., Noma, T., Honjo, T., Hatanaka, M. EMBO J. (1984) [Pubmed]
  30. Recombinant bacteriophages containing the integrated transforming provirus of Gardner--Arnstein feline sarcoma virus. Fedele, L.A., Even, J., Garon, C.F., Donner, L., Sherr, C.J. Proc. Natl. Acad. Sci. U.S.A. (1981) [Pubmed]
  31. Attenuation of bovine leukemia virus by deletion of R3 and G4 open reading frames. Willems, L., Kerkhofs, P., Dequiedt, F., Portetelle, D., Mammerickx, M., Burny, A., Kettmann, R. Proc. Natl. Acad. Sci. U.S.A. (1994) [Pubmed]
  32. A novel diagnostic method of adult T-cell leukemia: monoclonal integration of human T-cell lymphotropic virus type I provirus DNA detected by inverse polymerase chain reaction. Takemoto, S., Matsuoka, M., Yamaguchi, K., Takatsuki, K. Blood (1994) [Pubmed]
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