Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0019693 (HIV)
 170,526 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Large membrane-bound crystalline inclusions were seen on electron microscopic examination of the syncytiotrophoblast from the placenta of a HIV infected patient. The syncytium displayed abundant secretory granules (180-240 nm in diameter), with electron-dense centers (i.e., bull's eye granules or targetoid granules) which occasionally showed partial crystallization. Some crystals exhibited a periodicity of 9-10 nm. Electron-dense material was also seen in distended cisternae of the rough endoplasmic reticulum (RER). These granules correspond presumably to human placental lactogen (HPL) secretion, as seen on light microscopic immunoperoxidase stains. The morphological evidence is consistent with the idea that the crystals represent crystalline accumulation of secretory product (HPL), thus forming an analogy with crystal formation in other types of secretory cells. Ribosome-lamella complexes were seen in the many pericytes present in the capillaries of chorionic villi.
 ...
PMID:Endocrine secretory granules and crystals in the syncytiotrophoblast. 131 21

Ultrastructural studies suggest that cell surface alterations occur early during the course of HIV-1 infection of CD4+T-lymphoblastoid cells. Attachment and penetration of HIV resulted in formation of membrane discontinuities and pores and "ballooning." Distention of the endoplasmic reticulum occurred in some cells within the first hour after HIV infection, and this correlated with the numbers of virions bound at the cell surface. These results suggest that HIV virion components may directly damage the cell membrane.
 ...
PMID:Membrane alterations linked to early interactions of HIV with the cell surface. 136 Jan 83

Sulfation is a posttranslational modification of proteins which occurs on either the tyrosine residues or the carbohydrate moieties of some glycoproteins. In the case of secretory proteins, sulfation has been hypothesized to act as a signal for export from the cell. We have shown that the human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein precursor (gp160) as well as the surface (gp120) and transmembrane (gp41) subunits can be specifically labelled with 35SO42-. Sulfated HIV-1 envelope glycoproteins were identified in H9 cells infected with the IIIB isolate of HIV-1 and in the cell lysates and culture media of cells infected with vaccinia virus recombinants expressing a full-length or truncated, secreted form of the HIV-1 gp160 gene. N-glycosidase F digestion of 35SO4(2-)-labelled envelope proteins removed virtually all radiolabel from gp160, gp120, and gp41, indicating that sulfate was linked to the carbohydrate chains of the glycoprotein. The 35SO42-label was at least partially resistant to endoglycosidase H digestion, indicating that some sulfate was linked to complex carbohydrates. Brefeldin A, a compound that inhibits the endoplasmic reticulum to Golgi transport of glycoproteins, was found to inhibit the sulfation of the envelope glycoproteins. Envelope glycoproteins synthesized in cells treated with chlorate failed to incorporate 35SO42-. However, HIV glycoproteins were still secreted from cells in the presence of chlorate, indicating that sulfation is not a requirement for secretion of envelope glycoproteins. Sulfation of HIV-2 and simian immunodeficiency virus envelope glycoproteins has also been demonstrated by using vaccinia virus-based expression systems. Sulfation is a major determinant of negative charge and could play a role in biological functions and antigenic properties of HIV glycoproteins.
 ...
PMID:Sulfation of the human immunodeficiency virus envelope glycoprotein. 143

CD4 is an integral membrane glycoprotein which is known as the human immunodeficiency virus (HIV) receptor for infection of human cells. The protein is synthesized in the endoplasmic reticulum (ER) and subsequently transported to the cell surface via the Golgi complex. HIV infection of CD4+ cells leads to downmodulation of cell surface CD4, due at least in part to the formation of stable intracellular complexes between CD4 and the HIV type 1 (HIV-1) Env precursor polyprotein gp160. This process "traps" both proteins in the ER, leading to reduced surface expression of CD4 and reduced processing of gp160 to gp120 and gp41. We have recently demonstrated that the presence of the HIV-1-encoded integral membrane protein Vpu can reduce the formation of Env-CD4 complexes, resulting in increased gp160 processing and decreased CD4 stability. We have studied the effect of Vpu on CD4 stability and found that Vpu induces rapid degradation of CD4, reducing the half-life of CD4 from 6 h to 12 min. By using a CD4-binding mutant of gp160, we were able to show that this Vpu-induced degradation of CD4 requires retention of CD4 in the ER, which is normally accomplished through its binding to gp160. The involvement of gp160 in the induction of CD4 degradation is restricted to its function as a CD4 trap, since, in the absence of Env, an ER retention mutant of CD4, as well as wild-type CD4 in cultures treated with brefeldin A, a drug that blocks transport of proteins from the ER, is degraded in the presence of Vpu.
 ...
PMID:Human immunodeficiency virus type 1 Vpu protein induces rapid degradation of CD4. 143 12

The cell surface glycoprotein, CD4, is the receptor for human immunodeficiency virus (HIV) in T lymphocytes. Following HIV infection, there is reduced expression of CD4 on the cell surface, and this downregulation probably results, at least in part, from the formation of complexes containing the HIV type 1 (HIV-1) glycoprotein precursor (gp160) and CD4 that are not transported from the endoplasmic reticulum (ER). At the plasma membrane of T cells, CD4 is tightly associated with a cytoplasmic tyrosine kinase (p56lck) that is involved in T-cell activation. Using a transient expression system with HeLa cells, we show by pulse-labeling and immunoprecipitation that newly synthesized CD4 can associate with p56lck before CD4 is transported from the ER. In the presence of HIV-1 gp160, a ternary complex of gp160-CD4 and p56lck forms in the ER. Using confocal immunofluorescence microscopy, we observed complete retention of p56lck in the ER. Such mislocation of a tyrosine kinase to the cytoplasmic face of the ER could play a role in lymphocyte killing caused by HIV infection or expression of gp160 alone.
 ...
PMID:Human immunodeficiency virus type 1 glycoprotein precursor retains a CD4-p56lck complex in the endoplasmic reticulum. 154 63

The processing and secretion of the envelope glycoproteins of human immunodeficiency virus type 1 (HIV-1) were studied in chronically infected T cells and in primary macrophages treated with an antiviral antibiotic brefeldin A (BFA). BFA blocks the egress of proteins from the endoplasmic reticulum and has a profound effect on the structure of cis/medial Golgi. In MOLT-3 cells infected with the IIIB strain of HIV-1 (MOLT-3/IIIB), BFA inhibited the intracellular processing of gp160. The secretion of envelope proteins from these cells was significantly inhibited in the presence of BFA. The gag proteins, on the other hand, were processed and secreted normally. BFA also inhibited the proteolytic processing of gp160 in primary macrophages infected with HIV-1. The infectivity of virus pelleted from the medium of MOLT-3/IIIB cells treated with BFA was markedly lower than that obtained from untreated cells. These results demonstrate that the proteolytic processing of gp160 in HIV-1-infected cells takes place after the glycoprotein exists the endoplasmic reticulum and that the transport of glycoprotein to the cell surface is required for assembly of complete HIV-1 particles.
 ...
PMID:Brefeldin A inhibits the processing and secretion of envelope glycoproteins of human immunodeficiency virus type 1. 171 46

Intracellular transport and processing of the human immunodeficiency virus type 1 (HIV-1) envelope precursor glycoprotein, gp160, proceeds via the endoplasmic reticulum and Golgi complex and involves proteolytic processing of gp160 into the mature virion components, gp120 and gp41. We found that coexpression of gp160 and human CD4 in HeLa cells severely impaired gp120 production due to the formation of intracellular gp160-CD4 complexes. This CD4-mediated inhibition of gp160 processing was alleviated by coexpression of the HIV-1-encoded Vpu protein. The coexpression of Vpu and CD4 in the presence of gp160 resulted in increased degradation of CD4. Although the precise mechanism(s) responsible for the Vpu effect is presently unclear, our findings suggest that Vpu may destabilize intracellular gp160-CD4 complexes.
 ...
PMID:Human immunodeficiency virus type 1 Vpu protein regulates the formation of intracellular gp160-CD4 complexes. 172 86

Intracellular transport and processing of the human immunodeficiency virus type 1 (HIV-1) envelope precursor polyprotein, gp160, proceeds via the endoplasmic reticulum (ER) and Golgi complex. We examined gp160 processing during the production of HIV-1 virions in transfected HeLa cells using wild-type and env mutant proviral molecular clones. Results from pulse-chase analyses indicated that a single amino acid substitution within a highly conserved domain of the env gene impaired gp160 export from the ER, leading to an increase in oligomeric forms of gp160 and a decrease in gp120 production. In contrast, gp160 which contained a mutated cleavage site was able to traverse the ER/Golgi complex, even in the absence of proteolytic processing, and become incorporated into budding virions. These findings indicate that export from the ER is a point in the intracellular trafficking of gp160 that is crucial to the production of the mature envelope components.
 ...
PMID:Mutations within the human immunodeficiency virus type 1 gp160 envelope glycoprotein alter its intracellular transport and processing. 187 74

Human CD4+ T cell clones and cell lines were shown to lyse recombinant vaccinia virus-infected cells that synthesize the HIV-1 envelope glycoprotein gp160. The processing of endogenously synthesized gp160 for recognition by CD4+ T cells required that the protein, after synthesis on the rough endoplasmic reticulum and during subsequent cellular transport, remain attached to the luminal/extracellular membrane face by a hydrophobic anchor sequence.
 ...
PMID:Anchor sequence-dependent endogenous processing of human immunodeficiency virus 1 envelope glycoprotein gp160 for CD4+ T cell recognition. 196 6

Human immunodeficiency virus type 2 (HIV-2) is similar in genetic organization to HIV-1 but contains a unique gene (vpx) that encodes a 16-kDa protein. A replication-competent molecular clone of HIV-2 (HIV-2sbl/isy) that infects human primary cells in vitro and rhesus monkeys was used to generate three mutations in the vpx gene. In the first mutant, the vpx open reading frame was truncated at amino acid 20; the second mutant was tailored to eliminate the proline-rich carboxyl terminus of the protein; and the third mutant was obtained by addition of four amino acids (KDEL) to the carboxyl terminus of the protein to provide a retention signal in the endoplasmic reticulum. The viral infection kinetics of the three mutant viruses and isogeneic HIV-2sbl/isy in the SupT1 cell line were similar. Slight impairment in the early phases of viral replication was observed during infection of primary human peripheral blood mononuclear cells with the vpx mutant viruses. All of the vpx mutant viruses readily infected macrophages, indicating that vpx expression is dispensable for HIV-2 infection and replication in human macrophages.
 ...
PMID:Dispensable role of the human immunodeficiency virus type 2 Vpx protein in viral replication. 204 Nov 3


1 2 3 4 5 6 7 8 9 10 Next >>