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Query: UMLS:C0019693 (HIV)
 170,526 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Our previous studies have shown that human immunodeficiency virus type 1 (HIV-1), with mutations in accessory genes such as vif, vpr or vpu, can generate persistent infection of MT-4 cells, whereas infection by wild-type or nef mutant HIV-1 causes extensive cell death. The possibility of generating a naturally attenuated form of HIV-1 with reduced cytopathogenicity in MT-4 cells was examined by in vitro serial passage of the wild-type and a nef mutant form of HIV-1, each derived from the infectious molecular clone pNL432. The ability to cause persistent infection was observed after four passages of wild-type HIV-1 with the frequency of persistence becoming progressively higher with serial passage. In contrast, persistent infection was not observed even after 50 passages of the nef mutant virus. Sequence analysis of the accessory gene loci in genomes recovered from the persistent infections caused by passaged virus revealed mutations in vif and vpr, but not in vpu. The processing of the Env precursor to mature forms was not modified in any of the passages of either wild-type or nef mutant HIV-1. However, when compared with acute infections caused by similarly passaged virus of both wild-type and nef mutant HIV-1, persistent infections by passaged wild-type HIV-1 showed a significant decrease in the cell surface expression and function of Env. Cell surface CD4 was only partially down-regulated on cells acutely infected with the passaged viruses, whereas on cells persistently infected with passaged wild-type HIV-1 it was completely down-regulated. These results suggest that, during serial passage of HIV-1, mutations accumulate at least in the accessory genes vif and vpr in parallel with a lesser interaction between cell surface Env and CD4 molecules, and lead to the generation of less cytopathogenic viruses capable of persistent infection. Our results also suggest an important role for the nef gene product in the generation of HIV-1 strains that are less cytopathogenic.
J Gen Virol 1994 Sep
PMID:Persistent infection of MT-4 cells by human immunodeficiency virus type 1 becomes increasingly likely with in vitro serial passage of wild-type but not nef mutant virus. 752 92

Replication of human immunodeficiency virus type 1 (HIV-1) is restricted to CD4-expressing primate cells. This tropism may be due partly to the absence from nonprimate cells of a species-specific factor which has an accessory role to CD4 during virus penetration. In this study we describe a rat B lymphocyte cell line in which there is efficient CD4-dependent entry of HIV-1. However, this cell line has a block to productive infection of HIV-1 at a stage between reverse transcription and integration. Our results demonstrate that the putative accessory factor for HIV-1 penetration is not restricted to primate cells and that there is a novel, uncharacterized cell-virus interaction at a stage between penetration and integration.
J Gen Virol 1994 Oct
PMID:A rodent cell line permissive for entry and reverse transcription of human immunodeficiency virus type 1 has a pre-integration block to productive infection. 752 78

Interleukin-10 (IL-10), a product of T lymphocytes, B cells and macrophages, participates in Th-2 immune responses and modulates macrophage functions including possible interactions with pathogens. We have found that Chinese hamster ovary cell-derived human recombinant (hr) IL-10 inhibits human immunodeficiency virus type 1 strains Ada and Ba-L (HIV-1ADA and HIV-1Ba-L) replication in primary tissue culture-derived macrophages in a dose-dependent manner. Inhibition by IL-10 treatment (> 5 U/ml) was effective 72 h before or 24 h after infection and cytokine activity blocked by anti-hrIL-10 antibody (19F1), or lost after heat inactivation of IL-10. Viral production was measured by determining p24 and reverse transcriptase levels while reverse transcription kinetics for the long terminal repeat (LTR) and gag were assessed at timed intervals after infection and quantified by 32P end-labelling. IL-10 inhibited early steps of infection without modulating cell surface CD4+ levels. The onset of LTR reverse transcription was delayed by 4 to 8 h and the number of LTR transcripts was decreased by 77% at 24 h and by 87% 48 h after infection. IL-10 effects were reversible; after cytokine washout, cells treated before infection showed lower levels of virus compared with those treated after infection. IL-10 biological activity was confirmed in three virus-independent assays. These results demonstrate IL-10 decreases HIV-1 reverse transcription upon macrophage infection and subsequently mediates viral latency in vitro. Therefore, IL-10 may be involved in the effective control of HIV-1-infected macrophages in vivo.
J Gen Virol 1994 Dec
PMID:Interleukin-10 inhibits initial reverse transcription of human immunodeficiency virus type 1 and mediates a virostatic latent state in primary blood-derived human macrophages in vitro. 752 34

The env gene sequences of ten tissue-culture-adapted human immunodeficiency virus type 2 (HIV-2) isolates from West African patients were determined. Alignment and comparison of the gene sequences and putative translation products with database sequences revealed 11-29% diversity at the nucleotide level and 15-31% variation at the protein level. From analysis of glycoproteins of HIV-2 strains sensitive and resistant to neutralization by HIV-1 antisera, five regions were identified as putative targets for cross-neutralizing antibody. The HIV-2 equivalent of the HIV-1 V3 loop was not included in this number. However, three of the HIV-2 peptides aligned with regions identified as targets for broad neutralization of HIV-1 strains. These were the V2 and CD4-binding domains of gp120 and the Kennedy domain in gp41. Phylogenetic analysis of the env gene sequences, together with HIV-2 env gene sequences published in the Los Alamos database, support the identification of two distinct HIV-2 subtypes, HIV-2a and HIV-2b. The new sequences are located within the HIV-2a subtype and allow prediction of at least three genotypes, designated I-III. Some correlation of genotype with geographical origin of isolates was noted. Genotype I viruses originate from Guinea Bissau and group II viruses mainly originate from The Gambia. One isolate from Guinea Bissau, HIV-2CAM4, appears phylogenetically older than other viruses in the HIV-2a subtype. The possible implications of this in the light of epidemiological findings in Guinea Bissau are discussed.
J Gen Virol 1995 Feb
PMID:Human immunodeficiency virus type 2 (HIV-2) env gene analysis: prediction of glycoprotein epitopes important for heterotypic neutralization and evidence for three genotype clusters within the HIV-2a subtype. 753 Dec 16

High-level expression vector pAZ was constructed for in vivo delivery of bioactive recombinant proteins, antigenic determinants, among other things. This vector meets the requirements to construction of recombinant bacteria as live oral carriers. It has a strong constitutive promoter, high stability in E.coli and vaccine strain Salmonella cells, and, moreover, encodes in addition for the marker protein (beta-galactosidase) which will later help follow up the fate of bacterial carriers and their interactions in the microorganism. Several recombinant plasmids encoding for beta-galactosidase variants with insertions of short fragments of HIV-1 gp41 and gp120 proteins, which were previously shown to be antigenic determinants, have been constructed on the basis of pAZ. E.coli and vaccine strain Salmonella cells were transformed by recombinant plasmids. To a considerable extent the level of hybrid protein synthesis depends on the structure of the antigenic determinant inserted. The maximal level of synthesis in E.coli is 16%. This hybrid protein could be isolated and purified (up to 90%) with the yield of 4 to 6 mg/g of wet cells. Almost all the hybrid proteins were immunologically reactive, as shown by ELISA with nonfractionated lysates and purified hybrids. In both strains in vitro stability of the vector and recombinant plasmids was at least 90% after 10 passages (about 140 generations) under random conditions. This paper sums up the first stage of construction of recombinant bacteria as live oral carriers.
Mol Gen Mikrobiol Virusol
PMID:[Design of an expression vector for delivery of in vivo recombinant biologically active proteins. 1. Synthesis of the antigenic determinant of HIV-1 gp120 and gp41 proteins in enterobacteria]. 753 56

Although the human immunodeficiency virus type 1 (HIV-1) nef gene still has no precisely defined function, in vivo studies have demonstrated that Nef is an important pathogenic determinant of HIV. In order to identify cellular proteins capable of binding to Nef, the HIV-1LAI nef gene product was expressed in the bacterial vector pGEX-2T as a glutathione S-transferase (GST)-Nef fusion protein. Deletion mutants corresponding to 86 and 35 N-terminal residues of the Nef protein were prepared. The GST-Nef constructs were used to identify cellular kinases capable of interacting with Nef. After incubation with a Jurkat cell lysate, the GST-Nef constructs immobilized on glutathione-agarose beads bound to cellular kinase(s) and were phosphorylated at three sites in vitro: one on threonine at position 15, one on serine between residues 1 and 35, and one on threonine between residues 36 and 86. The Nef-phosphorylating activity was inhibited by protein kinase C (PKC)-selective inhibitors. Cell fractionation showed that this Nef-binding kinase was mainly in the membrane-associated fraction. These results suggest that kinase(s) of the PKC family are specifically bound to and phosphorylate Nef in vitro. The interaction of Nef with cellular kinases and its phosphorylation may be important in mediating the effects of Nef in HIV-1 pathogenesis.
J Gen Virol 1995 Jun
PMID:In vitro binding and phosphorylation of human immunodeficiency virus type 1 Nef protein by serine/threonine protein kinase. 754 Jan 94

The CD4 molecule serves as the principal cell surface receptor common to both the human and simian immunodeficiency viruses (HIV-1, HIV-2 and SIV). Since binding to CD4 is not sufficient to permit virus entry, HIV 'co-receptors' have been implicated in mediating the fusion of viral and cellular membranes necessary for completing the entry process. In order to identify candidate co-receptor molecules, a panel of monoclonal antibodies (MAbs) directed against adhesion molecules was tested for the ability of the MAbs to inhibit HIV-1-induced cell fusion (syncytium formation) and HIV-1 entry. Certain antibodies directed against CD18, CD11b and CD11c inhibited HIV-1-induced syncytium formation but not entry, in agreement with previous reports. Interestingly, certain antibodies to ICAM-3 (intercellular adhesion molecule 3) (CD50) significantly inhibited HIV-1-specific entry but not syncytium formation using human SupT1 cells. Only one antibody directed against ICAM-3 significantly inhibited HIV-1-induced syncytium formation, entry and infectivity. Our results suggest that certain epitopes of ICAM-3 may be involved in mediating HIV-1-specific entry into lymphoid and monocytoid cells.
J Gen Virol 1995 Jun
PMID:Intercellular adhesion molecule 3, a candidate human immunodeficiency virus type 1 co-receptor on lymphoid and monocytoid cells. 754 Jan 95

We constructed a series of human immunodeficiency virus 1 (HIV-1)/simian immunodeficiency virus strain mac (SIVmac) chimeric viruses having vpr and/or nef genes of either HIV-1 or SIVmac based on a chimeric virus with LTRs, gag, pol, vif and vpx derived from SIVmac and tar, rev, vpu and env from HIV-1. All of the chimeric viruses replicated in human and macaque peripheral blood mononuclear cells (PBMCs) and in several CD4+ human cell lines, though their growth potentials were slightly different depending on whether vpr and nef were from HIV-1 or SIVmac, or were defective. The presence of nef accelerated replication in all the cells used and the replication of each chimera appeared to reflect that of the parental virus from which nef was derived. The presence of vpr had no clear effect in human and monkey PBMCs, but the replication of each chimera was influenced by the origin of vpr in H9 and A3.01 cells. NM-3rN, which carries HIV-1 vpr and SIVmac nef, was inoculated intravenously into three rhesus monkeys, three cynomolgus monkeys and two pig-tailed monkeys. From 2 to 14 weeks after inoculation, viruses were consistently re-isolated from all the monkeys and virus loads were as high as that of SIVmac reported previously. The results indicate that infection with NM-3rN is more efficient than any of our previous chimeric viruses and suggest that NM-3rN, having HIV-1 Env, will be a useful challenge virus for evaluating AIDS vaccines based on HIV-1 Env in macaque monkeys instead of chimpanzees.
J Gen Virol 1995 Sep
PMID:Construction of human immunodeficiency virus 1/simian immunodeficiency virus strain mac chimeric viruses having vpr and/or nef of different parental origins and their in vitro and in vivo replication. 756 55

We have investigated the in vivo state of feline immunodeficiency virus (FIV) transcription in peripheral blood mononuclear cells (PBMC) of chronically FIV-infected, asymptomatic cats. FIV was detected in a high percentage of PBMC but not in the plasma of these cats. By quantitative reverse transcription-PCR (RT-PCR) analysis. FIV transcriptional status in the PBMC was characterized by extremely low or undetectable levels of unspliced or singly spliced mRNAs and predominantly multiply spliced mRNAs. Upon stimulation in vitro, however, the larger mRNA species and infectious virus production were rapidly induced in the PBMC. Furthermore, we demonstrated that viral production was induced in association with differential increases in the levels of each multiply spliced mRNA coding for FIV regulatory proteins. From these results, we suggest that replication of FIV is blocked at an early stage of gene expression in vivo, as described in asymptomatic human immunodeficiency virus (HIV) -infected patients, and that FIV infection in cats may be a useful model for clinical latency of HIV infection in man. Moreover, we propose that the replication of FIV in vivo may be controlled by the differential expression of each multiply spliced mRNA.
J Gen Virol 1995 Sep
PMID:Temporal patterns of feline immunodeficiency virus transcripts in peripheral blood cells during the latent stage of infection. 756 56

The scope and importance of biliary infections from both a clinical and scientific perspective is rapidly changing. During this past year, considerable attention in the literature has focused on infections that are increasing in frequency in the United States and throughout the world, as a result of evolving demographics and continued spread of the acquired immunodeficiency syndrome epidemic. Pyogenic cholangitis remains a challenge for us to treat and significant controversy remains regarding optimal management. The myriad hepatobiliary manifestations of human immunodeficiency virus infection have led to a resurgence in the interest in parasitic and viral infections. Our understanding of infections and their pathogenesis and sequelae has progressed, although there are still many important questions that remain unanswered.
Curr Opin Gen Surg 1993
PMID:Biliary infections. 758 87


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