Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P51532 (transcriptional activator)
 6,546 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The E26 avian leukemia virus encodes a transcriptional activator-type oncoprotein consisting of Gag, Myb, and Ets domains, and transforms early erythroid cells as well as myeloblasts. Surprisingly, we have found that "early erythroid" transformants obtained in culture are multipotent, since they can be induced to differentiate into myeloblasts and eosinophils after superinfection with retroviruses containing kinase-type or ras oncogenes. In addition, TPA is an efficient inducer that generates predominantly eosinophils at low concentrations and myeloblasts at high concentrations. The determination process involves the complete extinction of erythroid/thrombocytic markers and the subsequent activation of myelomonocytic/eosinophilic properties, including the acquisition of specific growth factor requirements. "Erythroleukemic" cells from virus-infected animals were likewise found to be multipotent, making this a unique system to study the genesis of stem cell leukemias and the molecular basis of lineage commitment during hematopoiesis.
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PMID:Chicken "erythroid" cells transformed by the Gag-Myb-Ets-encoding E26 leukemia virus are multipotent. 132 47

The tax gene product (Tax protein) of human T-cell leukemia virus type I (HTLV-I) is a specific transcriptional activator of the viral long terminal repeat sequence and is essential for the replication cycle of the virus. To elucidate the relationship between the presence of anti-Tax antibody and the transmission of the viral infection, annual consecutive serum samples from married couples serologically discordant or concordant for HTLV-I were examined. These included 5 individuals whose spouses seroconverted during this 5-year follow-up study period. The samples were tested by a Western blot assay using a recombinant Tax protein as the antigen. The results showed that 24 of 32 (75%) men in the concordant couples (both husband and wife were HTLV-I carriers) had anti-Tax antibody, while only 5 of 18 (27.8%) men in the discordant couples (husband was carrier and wife was seronegative to HTLV-I) were positive for anti-Tax antibody (P = 0.0012). Furthermore, all spouses of the 5 seroconverters (4 women and 1 man) had anti-Tax antibody, while only 23 of 46 (50%) age-matched randomly selected HTLV-I carriers from the discordant-couple group had anti-Tax antibody. When the data were analyzed by gender, all husbands of the female seroconverters had anti-Tax antibodies, which was significantly higher than the prevalence of anti-Tax antibodies in men who did not transmit the virus to their spouses during the follow-up period (P = 0.017). In addition, antibody reactivity to other HTLV-I antigens (including Env gp46, transmembrane protein gp21, and Gag p19 and p24) were examined. The results indicated no significant differences between the prevalence of antibody reactivity to any of the antigens in the spouses of the seroconverters and the reference group. We conclude that the presence of anti-Tax antibody in men may indicate a high risk of viral transmission to their wives via heterosexual routes.
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PMID:Sexual transmission of human T-cell leukemia virus type I associated with the presence of anti-Tax antibody. 199 21

Visna virus is an ungulate lentivirus that is distantly related to the primate lentiviruses, including human immunodeficiency virus type 1 (HIV-1). Replication of HIV-1 and of other complex primate retroviruses, including human T-cell leukemia virus type I (HTLV-I), requires the expression in trans of a virally encoded post-transcriptional activator of viral structural gene expression termed Rev (HIV-1) or Rex (HTLV-I). We demonstrate that the previously defined L open reading frame of visna virus encodes a protein, here termed Rev-V, that is required for the cytoplasmic expression of the incompletely spliced RNA that encodes the viral envelope protein. Transactivation by Rev-V was shown to require a cis-acting target sequence that coincides with a predicted RNA secondary structure located within the visna virus env gene. However, Rev-V was unable to function by using the structurally similar RNA target sequences previously defined for Rev or Rex and, therefore, displays a distinct sequence specificity. Remarkably, substitution of this visna virus target sequence in place of the HIV-1 Rev response element permitted the Rev-V protein to efficiently rescue the expression of HIV-1 structural proteins, including Gag, from a Rev- proviral clone. These results suggest that the post-transcriptional regulation of viral structural gene expression may be a characteristic feature of complex retroviruses.
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PMID:Visna virus encodes a post-transcriptional regulator of viral structural gene expression. 217 Sep 81

Human T-cell leukemia virus type 1 (HTLV-1) is associated with leukemia/lymphoma and neurologic disorders. Although the viral transcriptional activator Tax is the critical viral oncoprotein, Rex, which regulates the expression of the viral structural and enzymatic genes, is essential for efficient viral replication. Herein, we investigate the contribution of Rex in HTLV-1 immortalization of primary T cells in vitro and viral survival in an infectious rabbit animal model. A Rex-deficient HTLV-1 (HTLVRex-) was constructed and characterized for viral gene expression, protein production, and immortalization capacity. Cells transiently transfected with the HTLVRex- proviral clone produced low detectable levels of p19 Gag. 729HTLVRex- stable transfectants produced functional Tax, but undetectable levels of Rex or p19 Gag. Coculture of irradiated 729HTLVRex- cells with peripheral blood mononuclear cells (PBMCs) resulted in sustained interleukin-2 (IL-2)-dependent growth of primary T lymphocytes. These cells carried the HTLVRex- genome and expressed tax/rex mRNA but produced no detectable Rex or p19 Gag. Rabbits inoculated with irradiated 729HTLVRex- cells or 729HTLVRex- cells transiently transfected with a Rex cDNA expression plasmid failed to become persistently infected or mount a detectable antibody response to the viral gene products. Together, our results provide the first direct evidence that Rex and its function to modulate viral gene expression and virion production is not required for in vitro immortalization by HTLV-1. However, Rex is critical for efficient infection of cells and persistence in vivo.
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PMID:HTLV-1 Rex is required for viral spread and persistence in vivo but is dispensable for cellular immortalization in vitro. 1290 36

The retroviral phenomenon of superinfection resistance (SIR) defines an interference mechanism that is established after primary infection, preventing the infected cell from being superinfected by a similar type of virus. This review describes our present understanding of the underlying mechanisms of SIR established by three characteristic retroviruses: Murine Leukaemia Virus (MuLV), Foamy Virus (FV), and Human Immunodeficiency Virus (HIV). In addition, SIR is discussed with respect to HIV superinfection of humans. MuLV resistant mice exhibit two genetic resistance traits related to SIR. The cellular Fv4 gene expresses an Env related protein that establishes resistance against MuLV infection. Another mouse gene (Fv1) mediates MuLV resistance by expression of a sequence that is distantly related to Gag and that blocks the viral infection after the reverse transcription step. FVs induce two distinct mechanisms of superinfection resistance. First, expression of the Env protein results in SIR, probably by occupancy of the cellular receptors for FV entry. Second, an increase in the concentration of the viral Bet (Between-env-and-LTR-1-and-2) protein reduces proviral FV gene expression by inhibition of the transcriptional activator protein Tas (Transactivator of spumaviruses). In contrast to SIR in FV and MuLV infection, the underlying mechanism of SIR in HIV-infected cells is poorly understood. CD4 receptor down-modulation, a major characteristic of HIV-infected cells, has been proposed to be the main mechanism of SIR against HIV, but data have been contradictory. Several recent studies report the occurrence of HIV superinfection in humans; an event associated with the generation of recombinant HIV strains and possibly with increased disease progression. The role of SIR in protecting patients from HIV superinfection has not been studied so far. The phenomenon of SIR may also be important in the protection of primates that are vaccinated with live attenuated simian immunodeficiency virus (SIV) against pathogenic SIV variants. As primate models of SIV infection closely resemble HIV infection, a better knowledge of SIR-induced mechanisms could contribute to the development of an HIV vaccine or other antiviral strategies.
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PMID:Retroviral superinfection resistance. 1610 23

The human immunodeficiency virus type 1 (HIV-1) is a primate lentivirus that causes the acquired immunodeficiency syndrome (AIDS). In addition to the virion structural proteins and enzyme precursors, that are Gag, Env and Pol, HIV-1 encodes several regulatory proteins, notably a small nuclear transcriptional activator named Tat. The Tat protein is absolutely required for virus replication since it controls proviral DNA transcription to generate the full-length viral mRNA. Tat can also regulate mRNA capping and splicing and was recently found to interfere with the cellular mi- and siRNA machinery. Because of its extensive interplay with nucleic acids, and its basic and disordered nature we speculated that Tat had nucleic acid-chaperoning properties. This prompted us to examine in vitro the nucleic acid-chaperoning activities of Tat and Tat peptides made by chemical synthesis. Here we report that Tat has potent nucleic acid-chaperoning activities according to the standard DNA annealing, DNA and RNA strand exchange, RNA ribozyme cleavage and trans-splicing assays. The active Tat(44-61) peptide identified here corresponds to the smallest known sequence with DNA/RNA chaperoning properties.
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PMID:The HIV-1 transcriptional activator Tat has potent nucleic acid chaperoning activities in vitro. 1844 94