Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0035412 (rhabdomyosarcoma)
 6,156 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

DNA sequence analyses of several human immunodeficiency virus (HIV) isolates revealed extensive genetic diversity in the env gene and, to a lesser extent, in other regions of the viral genome, including the long terminal repeat (LTR) sequences. Since the LTRs contain elements responsible for the control of transcription, the difference in the LTR region may play a crucial role in the overall replication rate of HIV. To evaluate the role of the LTR, we have constructed a number of infectious hybrid HIV molecular clones containing LTRs from different proviral DNAs linked to the body of the viral genome, and analyzed them in a transient expression system. Both parental and hybrid proviral DNAs were transfected into human rhabdomyosarcoma cells for monitoring virus production. Proviral DNA designate pZ6 (HIVZr6) showed a high level of virus in the medium of the transfected culture in comparison to the pHXB2 (HIVHTLV-III) and pARV (HIVSF-2) DNAs. Hybrid proviral DNAs containing viral genes from pZ6, linked to LTR U3 sequences of pHXB2 and pARV at the 5' end, showed virus production similar to the levels observed with pZ6. These results indicate that the extent of virus production does not correlate with the LTR U3 sequences, and may involve other regions of the viral genome.
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PMID:Structure-function studies of HIV-1: influence of long terminal repeat U3 region sequences on virus production. 135 91

Human immunodeficiency viruses (HIV) isolated from infected individuals show tremendous genetic and biologic diversity. To delineate the genetic determinants underlying specific biologic characteristics, such as rate of replication, cytopathic effects, and ability to infect macrophages and T4 lymphoid cells, generation of hybrid HIV using viruses which exhibit distinct biologic features is essential. To develop methods for generating hybrid HIV, we constructed truncated HIV proviral DNA plasmids. Upon digestion with restriction enzymes, these plasmid DNAs were cotransfected into human rhabdomyosarcoma cells to generate hybrid HIV. The hybrid HIVs derived by this method were infectious upon transmission to both phytohemagglutinin-stimulated peripheral blood lymphocytes and established human leukemic T-cell lines. The virus derived from molecular clone pHXB2 (HIVHTLV-III) productively infected CEMx174 cells. On the other hand, molecular clone pARV (HIVSF2)-derived virus did not show productive infection of CEMx174 cells when used as a cell-free virus. The hybrid HIV containing the 3' end of the genome from pARV and the 5' end of the genome from pHXB2 was effective in infecting CEMx174 cells, but the converse hybrid containing 5' pARV and 3' pHXB2 was not effective in infecting CEMx174 cells. These results suggest that differences in the genes outside of env and nef play a role in the ability of the virus to infect a certain cell type. The intracellular ligation method should be useful in the analysis of related and unrelated HIV-1 isolates with common restriction enzyme cleavage sites.
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PMID:Generation of hybrid human immunodeficiency virus utilizing the cotransfection method and analysis of cellular tropism. 167 38

The mobile transgene constructs of most human immunodeficiency virus (HIV)-based lentivirus vectors currently in use contain viral long terminal repeats, a 5' untranslated region, gag sequences, and env sequences that include the Rev-responsive element (RRE). In this study, we examined the possibility of deleting HIV splice sites and gag and env sequences from an HIV type 1 recombinant vector established in our laboratory as part of our ongoing efforts to improve this vector system. Mutations in the major splice donor site (SD) markedly reduced viral RNA expression but had little effect on vector titer. Deletion of gag or env sequences, excluding RRE, led to a moderate reduction in vector titer. Interestingly, deletion of RRE slightly reduced viral RNA expression but markedly impaired vector function. Combined deletions of RRE, gag (except for the first 40 nucleotides), env, and the SD mutation resulted in a twofold increase in cytoplasmic viral RNA expression and a recovery of vector efficiency to approximately 50% of the wild-type level. This increase in cytoplasmic RNA levels is likely to be due, at least in part, to effects of the TE671 host cells, a human rhabdomyosarcoma cell line used for vector production in our system, on the cytoplasmic distribution of spliced and unspliced viral RNA. These results show that optimal lentivirus vector function can be maintained in the absence of multiple essential viral elements.
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PMID:Contributions of viral splice sites and cis-regulatory elements to lentivirus vector function. 1036 78

Gibbon ape leukemia virus (GALV) can infect a wide variety of cells but fails to infect most cells derived from laboratory mice. Transduction of human hematopoietic stem cells with GALV retroviral vectors is more efficient than with amphotropic vectors. In this study, a Moloney murine leukemia virus-gibbon ape leukemia virus (MoMLV-GALV) vector was constructed by replacing the natural env gene of the full-length Moloney MLV genome with the GALV env gene. To monitor viral transmission by green fluorescent protein (GFP) expression, internal ribosomal entry site-enhanced GFP (IRES-EGFP) was positioned between the GALV env gene and the 3' untranslated region (3' UTR) to obtain pMoMLV-GALV-EGFP. The MoMLV-GALV-EGFP vector was able to replicate with high titer in TE671 human rhabdomyosarcoma cells and U-87 human glioma cells. To evaluate the potential of the MoMLV-GALV vector as a therapeutic agent, the gene for the fusogenic envelope G glycoprotein of vesicular stomatitis virus (VSV-G) was incorporated into the vector. Infection with the resulting MoMLV-GALV-VSV-G vector resulted in lysis of the U-87 cells due to syncytium formation. Syncytium formation was also observed in the transfected human prostate cancer cell line LNCaP after extended cultivation of cells. In addition, we deleted the GALV env gene from the MoMLV-GALV-VSV-G vector to improve viral genome stability. This MoMLV-VSV-G vector is also replication competent and induces syncytium formation in 293T, HT1080, TE671 and U-87 cells. These results suggest that replication of the MoMLV-GALV-VSV-G vector or MoMLV-VSV-G vector may directly lead to cytotoxicity. Therefore, the vectors developed in this study are potentially useful tools for cancer gene therapy.
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PMID:Construction of a replication-competent retroviral vector for expression of the VSV-G envelope glycoprotein for cancer gene therapy. 3214 6

ABSTRACT The prototype fowl glioma-inducing virus (FGVp) causes fowl glioma and cerebellar hypoplasia in chickens. In this study, we investigated whether a strain of avian leukosis virus (ALV), associated with avian osteopetrosis and mesenchymal neoplasms, is able to induce fowl glioma. We encountered avian osteopetrosis and mesenchymal neoplasms, including myxosarcoma and rhabdomyosarcoma, in Japanese native chickens used for both egg-laying and meat production. These birds were also affected by non-suppurative encephalitis and glioma in their brains. Four ALV strains (GifN_001, GifN_002, GifN_004, GifN_005) were isolated, and a phylogenic analysis of envSU showed that these isolates were classified into different clusters from FGVp and the variants previously reported. Whereas the envSU shared a high identity (94.7%) with that of Rous sarcoma virus (strain Schmidt-Ruppin B) (RSV-SRB), the identity between envTM of GifN_001 and that of FGVp was high (94.5%), indicating that GifN_strains may emerge by recombination between FGVp and other exogenous ALVs. Specific-pathogen-free chickens inoculated in ovo with GifN_001 revealed fowl glioma and cerebellar hypoplasia. These results suggest that the newly isolated strains have acquired neuropathogenicity to chickens.
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PMID:Neuropathogenicity of newly isolated avian leukosis viruses from chickens with osteopetrosis and mesenchymal neoplasms. 3230 29