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Query: UMLS:C0021051 (immunodeficiency)
 71,517 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The envelope proteins of retroviruses are derived from a polypeptide precursor protein by cleavage adjacent to a cluster of basic amino acids. Site-specific mutagenesis was used to construct a mutant of the human immunodeficiency virus type 1 (HIV-1) in which the arginine residue at the carboxy-terminus of the gp120 was changed to a threonine residue. This single substitution was sufficient to abolish all detectable cleavage of the gp160 envelope precursor polypeptide as well as virus infectivity. The gp160 was produced in normal quantities from a biologically active clone of the mutant virus after transfection into cos-1 cells. The mutant gp160 contained N-linked oligosaccharide chains with mannose-rich cores similar to those of the gp160 produced by the wild-type clone. Immunofluorescence assays showed that gp160 was transported to the surface of transfected CD4+ HeLa cells. No envelope proteins of known size could be detected in the media of cells transfected with the mutant virus, suggesting that functional virions were not formed. Binding of the mutant gp160 to the CD4 receptor molecule was unimpaired. Despite this and the presence of gp160 on the cell surface, neither growth of mutant-transfected CD4+ HeLa cells nor cocultivation of transfected cos-1 cells with H9 cells resulted in significant syncytium formation. The data indicate that the carboxy-terminal arginine residue of HIV-1 gp120 is necessary for envelope protein cleavage and suggest cleavage is important in the virus life cycle in both functional virus release and membrane fusion.
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PMID:Characterization of an HIV-1 point mutant blocked in envelope glycoprotein cleavage. 210 82

Feline immunodeficiency virus (FIV) structural proteins were identified using sera obtained from experimentally inoculated cats. Proteins analysed by both radioimmunoprecipitation and Western blotting were specific for FIV infection and failed to cross-react with either antisera to feline leukaemia virus of feline syncytium-forming virus. Western blot analysis of purified virus revealed immunoreactive proteins with apparent Mr of 65K, 50K, 40K, 32K, 24K, 15K and 10K. The major core structural proteins of the virus were isolated by reverse phase HPLC and the aminoterminal sequences of p10 and p24 were determined. Monoclonal antibodies specific for p24 suggested the presence of a precursor protein that could be detected in 35[S]methionine/cysteine-labelled, virus-infected cell extracts. This putative precursor protein possessed an apparent Mr of 50K (Pr50gag). Further analysis revealed the presence of two additional proteins of 130K and 40K. Experiments utilizing tunicamycin, endoglycosidase H and glycopeptidase F revealed that p130 and p40 exhibited properties characteristic of glycoproteins. Our studies also indicated that FIV is immunologically related to other lentiviruses.
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PMID:Biochemical and immunological characterization of the major structural proteins of feline immunodeficiency virus. 215 3

A 99-amino acid protein having the deduced sequence of the protease from human immunodeficiency virus type 2 (HIV-2) was synthesized by the solid phase method and tested for specificity. The folded peptide catalyzes specific processing of a recombinant 43-kDa GAG precursor protein (F-16) of HIV-1. Although the protease of HIV-2 shares only 48% amino acid identity with that of HIV-1, the HIV-2 enzyme exhibits the same specificity toward the HIV-1 GAG precursor. Fragments of 34, 32, 24, 10, and 9 kDa were generated from F-16 GAG incubated with the protease. N-terminal amino acid sequence analysis of proteolytic fragments indicate that cleavage sites recognized by HIV-2 protease are identical to those of HIV-1 protease. The verified cleavage sites in F-16 GAG appear to be processed independently, as indicated by the formation of the intermediate fragments P32 and P34 in nearly equal ratios. The site nearest the amino terminus is quite conserved between the two viral GAG proteins (...VSQNY-PIVQN...in HIV-1,...KGGNY-PVQHV...in HIV-2). In contrast, the putative second site (...IPFAA-AQQKG...) of HIV-2 GAG shares minimal sequence identity with site 2 of HIV-1 GAG (...SATIM-MQRGN...). These sequence variations in the substrates suggest higher order structural features that may influence recognition by the proteases. Pepstatin A inhibits HIV-2 protease, whereas 1,10-phenanthroline and phenylmethylsulfonylfluoride do not; these results are in agreement with the finding that proteases of HIV and other retroviruses are aspartyl proteases.
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PMID:Synthetic HIV-2 protease cleaves the GAG precursor of HIV-1 with the same specificity as HIV-1 protease. 217 55

Treatment of virions of human immunodeficiency virus type 1 (HIV-1) with ionic and nonionic detergents (NP-40, octylglucoside, sodium deoxycholate) exerted an effect on the virus uncommon for enveloped viruses: instead of solubilization, both glycoproteins (gp120 and gp41) were found in subviral particles, whereas the core protein p24 was found in the supernatant fluid after the removal of subviral particles by centrifugation. The matrix protein p17 and unprocessed molecules of the precursor protein p55 were associated with subviral particles. The above data confirm the proposed model of the HIV-I structural organization according to which glycoproteins are incorporated into the isometric matrix formed by protein p17. Our data indicate that the core protein p24 is not incorporated into the matrix and not associated with nucleocapsid proteins.
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PMID:[The characteristics of the interaction of the proteins comprising the virions of the human immunodeficiency virus type 1]. 221 52

A recombinant baculovirus carrying the gag gene but lacking the protease coding sequences of human immunodeficiency virus type 2 (HIV-2) has been constructed. When this recombinant baculovirus is used to infect insect cells, a high level of gag precursor protein, gag pr41, is expressed. Electron microscopy showed that the majority of gag pr41 was budding through the plasma membrane and being released into the culture medium in spherical virus-like particles with a diameter of approximately 100 nm. Metabolic labeling demonstrates that gag pr41 is myristylated. Our results demonstrated that HIV-2 gag pr41 can be assembled into virus-like particles in the absence of other HIV proteins. Rabbits immunized with purified gag pr41 particles produced high-titer antibody and Western blot analysis showed that anti-gag pr41 rabbit sera recognize p17, p24, and p55 gag proteins of HIV-1. These results show that gag pr41 particles are highly immunogenic and that gag proteins of HIV-1 and HIV-2 have similar antigenic epitopes.
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PMID:Expression of gag precursor protein and secretion of virus-like gag particles of HIV-2 from recombinant baculovirus-infected insect cells. 223 77

Protein myristoylation was first discovered in the catalytic subunit of adenosine 3',5'-cyclic monophosphate-dependent protein kinase. Subsequently, various cellular and viral myristoylated proteins were detected. In each case, the myristoyl moiety was found in an amide linkage with the amino terminal glycine residue of the modified proteins. The biological functions of protein myristoylation of various cellular protein, oncogene product, and viral structural proteins have been studied by many biochemists. Two of the most thoroughly studies myristoylated proteins are the transforming protein of Rous sarcoma virus, pp60v-src, and the proto-oncogene product, pp60c-src. Deletion, modification of the first 14 NH2-terminal amino acid of pp60v-src, or chemical antimyristoylation of the protein with N-myristoyl glycinal diethylacetal does not affect intrinsic tyrosine src-kinase activity, but prevents myristoylation and membrane association, and abolishes the transforming activity of the protein. Protein myristoylations of some viral structural proteins were also studied by many investigators, and X-ray crystallographic studies of poliovirus suggest that myristate moiety may play a central role in capsid assembly. Recently, human immunodeficiency virus, HIV-I, process a myristoylated p17gag protein, which is proteolytically derived from the NH2-terminus of a gag precursor protein, and its myristate moiety may be important for virus assembly. In this review, we detailed recent studies of the protein myristoylation in cellular regulation and virus proliferation.
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PMID:[Function of protein myristoylation in cellular regulation and viral proliferation]. 254 55

Visna virus is the prototype lentivirus, with a genome structure similar to that of the human immunodeficiency viruses HIV-1 and HIV-2. We have analysed in vitro the transcription pattern of this virus in lytic infections of choroid plexus cells. Northern blot analysis shows the presence of spliced subgenomic mRNA species of 4.9, 4.3, 4.0, 1.7 and 1.4 kb. Use of appropriate subgenomic probes shows that the first three of these species encode envelope protein (but also potentially the small open reading frames Q and S). The 1.7 kb RNA could contain S. In order to elucidate the translational coding potential of the smallest RNA, and to characterize further all the transcripts, S1 mapping was performed across those parts of the genome which were close to exon/intron boundaries. This allowed the definition of acceptor splice sites following both introns 1 and 2 as well as donor sites preceding intron 2. The data suggest that the 1.4 kb RNA encodes a protein derived from the F reading frame that may form part of a precursor protein and also contains sequences with some degree of homology to the rev (trs/art) protein of HIV, as well as a typical protease cleavage site between these sequences and the F protein.
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PMID:A transcriptional map of visna virus: definition of the second intron structure suggests a rev-like gene product. 254 79

Retroviral capsid proteins and replication enzymes are synthesized as polyproteins that are proteolytically processed to the mature products by a virus-encoded proteinase. We have purified the proteinase of human immunodeficiency virus (HIV), expressed in Escherichia coli, to approximately 90% purity. The purified enzyme at a concentration of approximately 20 nM gave rapid, efficient, and specific cleavage of an in vitro synthesized gag precursor protein. Purified HIV proteinase also induced specific cleavage of five decapeptide substrates whose amino acid sequences corresponded to cleavage sites in the HIV polyprotein but not of a peptide corresponding to a cleavage site in another retrovirus. Competition experiments with different peptides allowed a ranking of cleavage sites. Inhibition studies indicated that the HIV proteinase was inhibited by pepstatin A with an IC50 of 0.7 microM.
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PMID:Activity of purified biosynthetic proteinase of human immunodeficiency virus on natural substrates and synthetic peptides. 264 44

CD4 is an integral membrane glycoprotein that acts as the cellular receptor for human immunodeficiency virus (HIV). A cDNA encoding full-length CD4 was inserted into the genome of Autographa californica nuclear polyhedrosis virus under transcriptional regulation of the viral polyhedrin gene promoter. The recombinant virus was used to infect insect cells, which resulted in the abundant expression of CD4 as evaluated by flow cytometry and immunoblot analysis. Recombinant CD4 expressed on the surface of infected insect cells was immunologically indistinguishable from human CD4 when using 11 different anti-CD4 monoclonal antibodies. The extraction of infected cells by phase-transition separation with Triton X-114 followed by immunoaffinity chromatography yielded a single protein detected by NaDodSO4/PAGE using silver staining. N-terminal sequence analysis of the purified recombinant protein showed that CD4 produced in Sf9 cells is efficiently cleaved from the precursor protein. Immunoblot analysis under nondenaturing conditions showed that the purified protein reacted with the anti-CD4 monoclonal antibody Leu-3a. The potential use of the recombinant membrane-associated CD4 in anti-HIV therapy is discussed.
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PMID:Cell-surface expression and purification of human CD4 produced in baculovirus-infected insect cells. 268 21

To examine the potential role of the GAG precursor polyprotein in morphogenesis and assembly of the simian immunodeficiency virus (SIV), we have expressed the gag gene of SIVMac using a baculovirus expression vector. Infection of insect cells with recombinant virus containing the entire gag gene results in high expression of the GAG precursor protein, Pr57gag. The recombinant protein is myristylated and is released in the culture supernatant in an insoluble particulate form. A point mutation in the N-terminal glycine codon (Gly----Ala) inhibits myristylation. This mutated product is highly expressed but is not found in the culture supernatant. Electron microscopy and immunogold labelling of infected cells show that the native Pr57gag protein assembles into 100-120 nm virus-like particles that bud from the cell plasma membrane and are released in the culture supernatant. The unmyristylated protein also assembles into particulate structures which only accumulate inside the cells. These results demonstrate that the unprocessed GAG precursor of SIV can spontaneously assemble into particles in the absence of other viral proteins. Myristylation of the Pr57gag precursor is necessary for its association with the cell plasma membrane, for budding and for extracellular release.
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PMID:The GAG precursor of simian immunodeficiency virus assembles into virus-like particles. 268 54


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