Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0021051 (immunodeficiency)
 71,517 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The complete nucleotide sequence of the integrase (IN) protein coding region of the murine leukaemia virus (MLV) amphotropic strain 4070A is presented. The sequence comprises 1,224 nucleotides, encoding a 408-residue polypeptide of M(r) 46,312. Alignment of the inferred 4070A IN amino acid sequence with the IN proteins of other MLV showed that substitutions are confined largely to segments within the N- and C-terminal domains. In the N-terminal domain the majority of substitutions occur as contiguous 2- to 6-residue blocks, whereas in the C-terminal domain they occur as isolated entities except within a short segment characterized by deletions/insertions. Selection appears to act on the C-terminal 19 residues of IN rather than on the N-terminal residues of ENV (encoded by overlapping reading frames), suggesting a functional role for this segment. Phylogenetic analyses grouped the sequences into two clusters, one comprising IN from the amphotropic strain 4070A and three ecotropic MLV (CAS-BR-E, Moloney and Friend), the other consisting of IN from three ecotropic MLV (two radiation-induced viruses and AKV) and a mink cell focus-forming (MCF) MLV virus. The same dichotomy and cluster composition was obtained from analysis of the long terminal repeat (LTR) regions from these viruses (consistent with the functional interrelationship of IN and LTR) but not from analysis of envelope protein sequences (consistent with the functional independence of ENV proteins from both IN and LTR). Secondary structure predictions supported features determined from the catalytic domain of human immunodeficiency virus and avian sarcoma virus IN, and identified probable structures within the relatively long N- and C-terminal domains of MLV IN proteins.
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PMID:Nucleotide sequence of the murine leukaemia virus amphotropic strain 4070A integrase (IN) coding region and comparative structural analysis of the inferred polypeptide. 967 35

pCMV-NL(Deltapol) and pAKV-NL(Deltapol) expressed human immunodeficiency virus type 1 (HIV-1) gag and env under the regulation of the human cytomegalovirus (CMV) immediate-early (IE) promoter/enhancer and the endogenous AKV murine leukemia viral long terminal repeat (LTR), respectively. Analysis of the immune responses elicited by direct DNA injection of pCMV-NL(Deltapol) and pAKV-NL(Deltapol) in macaques indicated that generation of the humoral and T-cell proliferative responses correlated directly with the promoter strength of the vaccine DNAs. In Macaca mulatta, pCMV-NL(Deltapol) generated stronger humoral responses and T-cell proliferative responses to Gag and Env using less DNA and fewer number of injections than pAKV-NL(Deltapol). Similarly, in Macaca nemestrina pCMV-NL(Deltapol) elicited high humoral responses, which persisted long-term and were boostable. Injection of large amounts of pAKV-NL(Deltapol), in general, failed to produce antibody levels comparable to pCMV-NL(Deltapol). However, injection of a control animal with large amounts of vector DNA produced a generalized enzyme-linked immunosorbent assay (ELISA) reactivity to HIV-1. The results indicated that generation of high immune responses to HIV-1 cannot be achieved by increasing the vaccine DNA dose and may require high protein expression from the DNA by including a strong promoter or by the use of other boosting agents. Furthermore, safety concerns may arise with increasing the DNA dose that could need additional investigation.
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PMID:Effect of different promoters on immune responses elicited by HIV-1 gag/env multigenic DNA vaccine in Macaca mulatta and Macaca nemestrina. 1077 91