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

With the use of a sensitive sequence comparison algorithm, a homology has been suggested between the primary structures of simian immunodeficiency virus (SIV) p24 core protein and foot-and-mouth disease virus (FMD) VP2 coat protein. Since the FMD sequence is homologous to picornaviral VP2 sequences with known three-dimensional architecture and since the SIV p24 sequence can be convincingly aligned with that from human immunodeficiency virus (HIV), it was possible to predict an eight-stranded beta-barrel fold for the HIV core protein. From analogy with the known environments of the picornaviral coats, p24 sequence spans could be predicted as likely candidates for antibody attachment. These suggestions may be important for development of an AIDS vaccine.
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PMID:A possible homology between immunodeficiency virus p24 core protein and picornaviral VP2 coat protein: prediction of HIV p24 antigenic sites. 249 82

Serum specimens which originally exhibited a narrow (indeterminate) 24-kilodalton core protein (p24) or p24/p55 pattern of reactivity with human immunodeficiency virus (HIV) in the Western blot (immunoblot) test were studied to gather information on antibody specificity. A total of 12 specimens were initially reevaluated with an indirect immunofluorescence assay (IFA), three enzyme-linked immunosorbent assays (ELISAs), and Western blot analyses. Five of the specimens were IFA positive and contained anti-gp160/gp120 antibodies which were observed only when an HIV Western blot antigen rich in gp160 and gp120 was used. The remaining seven serum specimens were nonreactive by IFA and showed variable reactivity in HIV antibody ELISAs. The specimens did not cross-react with core antigens for human T-cell leukemia virus types 1 and 2 or contain detectable levels of HIV p24 antigen. The p24/p55 reactivity of six of the seven indeterminate specimens could be reduced or eliminated by preincubating the specimens with disrupted, HIV-infected H9 cells but not with uninfected H9 cells. The six specimens also exhibited discernible reactivity with recombinant HIV p24 antigen. When an additional 23 indeterminate specimens were assayed, all of the serum specimens were nonreactive by IFA while 65% (15 of 23) showed various degrees of reactivity with the recombinant p24 protein. There was no indication that any of the HIV core antibody reactivity was caused by HIV infection. Indeterminate results for five patients with specific p24 reactivity, who were retested after a period of weeks or months, remained indeterminate for HIV antibody with no significant change in ELISA or Western blot reactivity.
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PMID:Investigation of atypical western blot (immunoblot) reactivity involving core proteins of human immunodeficiency virus type. 250 54

The major core protein (p25) of the human immunodeficiency virus type 1 (HIV-1) was characterized by two-dimensional-gel isoelectric focusing. The p25 detectable in HIV-1-infected cells is composed of four species with related isoelectric points. This is due in part to the phosphorylated state of p25. The four species of p25 are expressed on the cell surfaces of infected cells, but only the two most basic species are incorporated into the HIV-1 virion. These findings emphasize the importance of p25 in understanding infection with HIV and might have implications for the development of vaccines.
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PMID:Cell surface expression of several species of human immunodeficiency virus type 1 major core protein. 250 23

It is generally believed that the gag gene product of human immunodeficiency virus type 1 (HIV-1) is processed into several core proteins by a virus-specific protease. We used deletion mutation analysis to study the role of HIV-specific protease in the processing of core proteins and its requirement for viral infectivity. Several mutant genomes with deletions in the protease gene were constructed. A mammalian cell line, COS-M6, transfected with the wild-type viral genome was shown to produce virions containing processed core proteins, while COS-M6 cells transfected with two mutated genomes could express only the core protein precursor, Pr56gag. The wild-type transfectant produced infectious virus; both transfectants expressing the mutated genomes also produced virions, and one of them still retained reverse transcriptase activity. However, the mutant viral particles were devoid of infectivity. Virions with a distinct central core and an electron-dense nucleoid budded out from the plasma membrane of COS-M6 cells transfected with the wild-type genome. In contrast, noninfectious virions that budded either into cytoplasmic vacuoles or out from the plasma membrane of COS-M6 cells transfected with mutant genomes contained ring-shaped nucleoids. These results indicate that the HIV-1 protease plays a role not only in the maturation of the core proteins but also in the assembly of the virus and thus is required for viral infectivity.
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PMID:Role of human immunodeficiency virus type 1-specific protease in core protein maturation and viral infectivity. 265 99

The core structure of retroviruses, including the human immunodeficiency virus (HIV), consists of proteins that are initially synthesized as polyprotein precursors and then processed by a virally encoded protease yielding the mature core polypeptides. To obtain sufficient quantities of the purified HIV core precursor p55 for detailed studies, a segment of HIV DNA encoding the full length core precursor polyprotein p55 was expressed in Saccharomyces cerevisiae using a plasmid containing a constitutive galactose promoter. The expression of this DNA produced a protein with an estimated molecular size of 55,000, as determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE); this protein was immunoreactive to anti-HIV p24 antisera. Following cell lysis, freezing, and thawing, the expressed protein was an insoluble aggregate that served as the starting material for the purification process. Solubilization of the insoluble p55 with guanidine HCl followed by phenyl-Sepharose column chromatography and high performance liquid chromatography resulted in a preparation of p55 that was greater than 95% pure by SDS-PAGE, immunoreactive to anti-HIV core protein antibodies, and completely soluble in aqueous solution. The expressed p55 appeared to be myristoylated as evidenced by the incorporation of radiolabel following incubation of recombinant yeast cells with [3H]myristic acid; in addition the amino terminus of the final purified protein was blocked. Proteolytic digestion of purified p55 with synthetic HIV protease yielded the predicted amino- and carboxyl-terminal products; these were confirmed by amino acid sequence analysis. In contrast, digestion of purified p55 by the protease derived from the avian myeloblastosis virus resulted in fragments that were different in size from those produced by the HIV protease. The availability of the purified, full length water-soluble HIV core precursor will be useful in identifying agents that inhibit its processing by the HIV protease.
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PMID:Purification and characterization of human immunodeficiency virus (HIV) core precursor (p55) expressed in Saccharomyces cerevisiae. 266 48

A new isolate of the human immunodeficiency virus (HIV) related to the HIV-2 strain was isolated from peripheral blood lymphocytes of an Ivory Coast patient with AIDS. This isolate referred to as HIV-2 EHO could be differentiated by its envelope precursor and external glycoprotein which are 20-kDa smaller than those of HIV-2 ROD isolate. Furthermore, the apparent molecular weight of the major core protein of HIV-2 EHO is 27 kDa instead of 26 kDa as in HIV-2 ROD isolate. In addition, the product of the vpx gene which is a characteristic feature of the HIV-2 strain, is 14 kDa in HIV-2 EHO compared with 16 kDa in HIV-2 ROD. In contrast to these, the envelope precursor of HIV-2 EHO forms a transient dimer its maturation as is the case for HIV-2 ROD. In both cases the transmembrane proteins are 36 kDa and exists as homodimers of 80 kDa. Endoglycosidase H digestion experiments indicated that the 20-kDa difference between the two HIV-2 isolates is not due to a difference in the number of N-linked oligosaccharide chains per polypeptide, since deglycosylated envelope precursors of HIV-2 ROD and EHO have an apparent molecular weight of 80 and 60 kDa, respectively. Partial proteolysis of the envelope precursors from the two isolates with Staphylococcus aureus V8 protease gave a distinct pattern of polypeptides. These results suggest that the differences between the external envelope proteins of the two HIV-2 isolates are due to their amino acid composition. Accordingly, polyclonal antibodies raised against HIV-2 ROD envelope do not recognize the corresponding envelope proteins of HIV-2 EHO by immunoblotting and immunoprecipitation assays. These data illustrate that analysis of viral proteins could be useful for a rapid characterization of new viral isolates and show the heterogeneity of HIV-2 isolates in West Africa.
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PMID:Characterization of an HIV-2-related virus with a smaller sized extracellular envelope glycoprotein. 268 62

Some patients with the acquired immunodeficiency syndrome (AIDS) have long-tract degeneration in the spinal cord. Spinal-cord sections showing degeneration were immunoreactive in 13 of 17 AIDS patients using rabbit antiserum to whole disrupted human immunodeficiency virus (HIV) or a mouse monoclonal antibody to HIV core protein p24. The immunostaining was in a few macrophages, multinucleated cells, gliomesenchymal-cells nodules, glial cells and vascular endothelial cells. Eleven of the positive cases had histopathologic evidence of long-tract vacuolar alterations associated with this immunoreactivity, and the two cases without vacuolar alterations had immunoreactive multinucleated cells and gliomesenchymal-cell nodules. Immunolocalization of HIV in the spinal cord correlated well with clinical signs and symptoms, although concomitant cerebral and systemic infections often obscured the significance of the spinal-cord findings in the clinical setting. HIV vasculitis could lead to myelitis and to the clinical appearance of long-tract signs and symptoms.
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PMID:Immunohistochemical localization of human immunodeficiency viral antigens in formalin-fixed spinal cords with AIDS myelopathy. 270 40

Although merging clinically within the spectrum of the AIDS dementia complex, vacuolar myelopathy is a pathologically distinct entity detected in up to 30% of autopsied patients succumbing to the late complications of human immunodeficiency virus type 1 (HIV-1) infection. Using immunohistochemistry and in situ hybridization to detect an HIV-1 core protein and viral mRNA, respectively, in tissue sections, and culture isolation to assess infectious virus in tissue homogenates, we found that vacuolar myelopathy was independent of productive HIV-1 infection of the spinal cord and brain. These results indicate that AIDS-associated vacuolar myelopathy is either not related directly to spinal cord HIV-1 infection or involves nonproductive infection and pathobiological processes distinct from those responsible for the multinucleated-cell inflammatory infiltrates that serve as histopathologic markers of productive CNS HIV-1 infection.
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PMID:Dissociation of AIDS-related vacuolar myelopathy and productive HIV-1 infection of the spinal cord. 273 16

Benzylated derivatives of peptides corresponding to residues 81 through 92 of the CD4 molecule [CD4-(81-92)] inhibit human immunodeficiency virus 1 (HIV-1)-induced cell fusion and infection in vitro. If such peptides are to be considered as candidates in the therapy of HIV infection, it is crucial to know if the anti-HIV efficacy of CD4-based peptides is limited to blockade of infection and virus-induced cell fusion or if other stages of the viral life cycle are affected by these compounds. Accordingly, an in vitro quantitative microassay for acute HIV infection was divided into two kinetic phases corresponding to the two general stages of the viral life cycle: (i) viral infection and (ii) transmission of virus and viral protein products through cell contact or release of free virions. CEM-SS cell cultures were treated with peptide during either the infection or the transmission phase of the assay. When peptides were present during the infection phase, inhibition of syncytium formation correlated with decreased expression of viral core protein p24 and lack of infectious cell centers when cells exposed to virus were washed and replated onto fresh uninfected indicator cells. These data are consistent with complete inhibition of viral infection when peptide is present only during initial exposure to virus. Unexpectedly, parallel inhibition of syncytium formation, decreased p24 levels, and inhibition of infectious cell center formation were also seen even when peptides were added as late as 48 hr after inoculation, during the transmission period of the assay. Since viral binding and penetration are completed well before 48 hr in this assay system, CD4-(81-92) peptide derivatives appear to exert a virostatic effect on cultures already infected with HIV-1, decreasing p24 production, cytopathicity, and cell-mediated infectivity.
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PMID:CD4 antigen-based antireceptor peptides inhibit infectivity of human immunodeficiency virus in vitro at multiple stages of the viral life cycle. 278 82

This paper describes the construction of a new heteromyeloma cell line designated CB-F7. The cell line was derived from xenogeneic somatic cell hybridization between normal human B lymphocytes and the murine HAT-sensitive P3X63Ag8/653 cell line. CB-F7 cells were characterized by rapid cell growth (doubling time about 16 h) and high cloning efficiencies in culture medium supplemented with 10% or 5% fetal calf serum, respectively. The karyotype of the cells consists of about 75-78 chromosomes as well as two chromosomal fragments. Fusions of the cells with human peripheral blood cells resulted in approximately 2-6 clones per 10(5) seeded lymphocytes. Furthermore, the cells are ouabain resistant and therefore suitable for fusions with EBV-transformed lymphoblastoid cell lines. Using CB-F7 as the parental cell line a number of specific human mAb producing hybrids were established. For the first time, we describe here the generation of hybrids secreting human monoclonal antibodies to human immunodeficiency virus (HIV). Two monoclonal antibodies of IgG type and one of IgM type reacted with the major core protein p25 and one IgG antibody reacted with the transmembrane protein gp41.
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PMID:The high efficiency, human B cell immortalizing heteromyeloma CB-F7. Production of human monoclonal antibodies to human immunodeficiency virus. 282 78


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