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

In developing therapeutic reagents for the control of HIV infection, it is necessary to screen candidate products in vitro for their ability to reduce or neutralize viral infection. Although the current literature describes numerous neutralization assays, no universally accepted standards have been adopted. In this article, we briefly review the available neutralization assays and describe in detail the methods we have selected in our laboratory for the screening and characterization of reagents with potential anti-HIV properties. After evaluating many different technical protocols and experimental procedures, we have found the syncytium inhibition and syncytial focus assays to be particularly useful and have found p24 gag antigen production to be an excellent objective measure of HIV infection under a variety of conditions. These assays proved reproducible and sensitive and are suitable for use in the majority of laboratories.
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PMID:Design, development, and interpretation of HIV neutralization assays. 172 97

PBMC cocultured with HIV-infected monocytes for 12 to 48 h released high levels of IFN activity. IFN titers were directly dependent upon time after virus infection and level of HIV replication in infected cells. IFN induction in PBMC was evident with HIV-infected monocytes and PBMC and with myeloid and lymphoblastoid cell lines with at least three different HIV strains. In HIV-infected cell line pairs in which virus infection occurs in both productive and restricted forms, IFN induction in PBMC occurred only with productive infection. IFN activity was acid stable and completely neutralized by antibodies against IFN-alpha. Induction of IFN required cell-cell contact between HIV-infected cells and PBMC, but was independent of MHC compatibility. With PBMC co-cultured with autologous HIV-infected monocytes, IFN induction was highly selective: IL-1 beta, IL-6, or TNF-alpha activity and mRNA were not detected. Cell surface determinants on HIV-infected monocytes that induced IFN in PBMC remained active after fixation in 4% paraformaldehyde. Both adherent and nonadherent PBMC produced IFN after coculture with HIV-infected monocytes. Ability to produce IFN by PBMC was not affected by depletion of T cell, NK cell, B cell, or monocyte subpopulations. The IFN activity produced by PBMC cocultured with HIV-infected cells was about 20-fold less active than equal quantities of rIFN-alpha 2b for inhibition of HIV replication in monocytes and at low concentrations enhanced virus growth. Clinical studies with HIV-infected patients and parallel findings in animal lentivirus disease suggest an adverse role for IFN in disease progression. Conditions for induction of IFN in the culture system described in this report may mimic those in the HIV-infected patient. Defining the molecular basis for IFN induction, the cells that produce IFN, and the altered biologic activity of this important cytokine may provide insight into the pathogenesis of HIV disease.
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PMID:Induction of IFN-alpha in peripheral blood mononuclear cells by HIV-infected monocytes. Restricted antiviral activity of the HIV-induced IFN. 172 62

A novel photodynamic procedure employing "preactivated" merocyanine 540 (P-MC 540) was assessed for its effectiveness in inactivating human immunodeficiency virus type 1 (HIV-1) and simian immunodeficiency virus (SIV). Merocyanine 540 was preactivated by exposure to laser light at 514 nm prior to addition to viruses or infected cells. Treatment of cell-free HIV-1 and SIV with P-MC 540 significantly reduced their ability to infect and kill MT-4 cells in vitro. Preactivated MC 540 treatment of in vitro HIV-1-infected human peripheral blood mononuclear cells also decreased viral infection as assessed by a reduction in the amounts of HIV-1 p24 antigen produced and in the number of HIV-1 antigen-positive cells. Indirect immunofluorescence assays of target cell binding showed that treatment of cell-free HIV-1 and SIV with P-MC 540 interfered with their ability to bind to CD4+ target cells. Immunoprecipitation with a monoclonal anti-CD4 antibody of P-MC 540-treated and radiolabeled HIV-1 incubated with soluble recombinant CD4 (srCD4) resulted in coprecipitation of HIV-1 viral p17 and p24 core antigens with the envelope gp120/CD4 complex, suggesting cross-linking of viral components. However, no significant decrease in the binding of treated HIV-1 to srCD4 was observed. Because of the antitumor and antiviral properties of P-MC 540, this photopreactivation procedure may represent a promising therapeutic means for controlling systemic malignancies and viral infections, and for eliminating viral contaminants in biological fluids. Unlike conventional phototherapy, this procedure does not require the delivery of light energy at the target sites following binding of the photosensitizing compounds.
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PMID:Preactivated merocyanine 540 inactivates HIV-1 and SIV: potential therapeutic and blood banking applications. 173 11

Human immunodeficiency virus-associated nephropathy (HIVAN) is a recognized clinical entity of unknown pathogenesis. A role for viral infection of renal cells in the initiation of this process at present is an intriguing but untested hypothesis. Studies in primate models of acquired immunodeficiency syndrome (AIDS) suggest that injury to the mesangial cell may be central to the sclerosing glomerular lesion characteristic of HIVAN. We therefore tested the infectibility of human mesangial cells (HMC) in vitro by a variety of strains of HIV chosen to include a spectrum of tropisms for different cell types. Productive infection of mesangial cells could not be demonstrated using any of the virus strains. Nonetheless, HIV infection of intrinsic renal cells remains an attractive area of inquiry for understanding the natural history of HIVAN.
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PMID:Human mesangial cells are resistant to productive infection by multiple strains of human immunodeficiency virus types 1 and 2. 173 93

One hundred hemophilia A and 30 hemophilia B patients who had been treated with non-heated and heated factor VIII or prothrombin complex concentrates were examined by immunological tests including Clq-bearing immune complexes assay. Antibodies to human immunodeficiency virus type 1 (HIV-1), hepatitis B virus (HBV), hepatitis C virus (HCV) and human parvovirus B19 (B19) were analyzed by Western blotting, enzyme immunoassay, passive hemagglutination or radio-immunoassay. Clq-bearing immune complexes were assayed by a monoclonal anti-Clq ELISA system (Immunomedics). Seropositivity to HIV-1, HBV, HCV, and B19 was 56.9%, 87.7%, 79.2% and 100% respectively. Clq-bearing immune complexes were positive in 109 of the 130 patients (83.8%). The positivity and the levels were extremely higher than those in normal individuals. Clq-bearing immune complex levels in patient positive for HIV-1, HCV, or HBV were higher than those in the negative group (HIV: P less than 0.001, HCV: P less than 0.005, HBV: P less than 0.05). When the patients were divided into four groups according to seropositivity to HIV-1 and/or HCV, Clq-bearing immune complex levels were the highest in the group positive for both antibodies, and the lowest in the group negative for both antibodies. These results suggested that each viral infection influences the formation of immune complexes and repeated viral infection increased the level of Clq-bearing immune complexes in these patients.
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PMID:[Elevated Clq-bearing immune complexes in hemophiliacs with viral infections]. 177 53

We have presented data supporting the view that HIV infection of T cells and monocytes proceeds via receptor-mediated endocytosis. Biochemical analysis of the pathway for internalization of 32P-labeled HIV revealed the presence of intact, intercellular virions and provided evidence for subsequent uncoating of these particles and release of viral RNA to the cytoplasm. Electron microscopy demonstrated virions within vesicles and documented fusion between viral and endosomal membranes. Others have provided evidence supporting the notion that endocytosis is not required for HIV infection. In consequence of this apparent paradox, it has been suggested that both mechanisms, i.e. direct fusion to the plasma membrane and endocytosis, are functional pathways for HIV entry. I do not favor this position. Examination of the biology of CD4, its role in lymphocyte activation, and its function as the receptor for HIV imply a more active role for this molecule in virus infection than simply as a transient anchor for fusion events. The principal experiment of concern is the report by Maddon, et al., that human CD4- expressing murine cell lines remain resistant to infection by VSV pseudotypes bearing the HIV envelope glycoprotein. This paper and a subsequent review of HIV entry by Marsh and Dalgleish comment on the possibility that endocytosis of human CD4 may not occur in murine cells hence, the block to infectious entry of these pseudotype virions. Resolution of the mechanism for HIV infection is more than rationalization or semantics. The pathway of endocytosis presents an unique feature of cell biology. Should HIV infection be proven to occur via this mechanism, then appropriate assays for novel classes of antiviral agents could be developed. Other features of the endosomal vesicle, such as the unique composition of its membrane or the possible presence of specific proteolytic activities might play important roles in HIV infection and thus, present new targets for the development of antiviral agents. Indeed, the synthetic liposome AL721 is an effective inhibitor of HIV infection in vitro. This antiviral agent probably acts by decreasing the cholesterol content of the virion envelope. It was shown previously that the envelope is specifically enriched in cholesterol, a property not associated with the plasma membrane but clearly involved in Semliki Forest virus fusion within the endosome.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:The endocytic pathway for human immunodeficiency virus infection. 178 41

In the first part of this article some structural and biological aspects of the HIV viruses are presented, in our opinion among the most interesting ones, connected with the AIDS viruses. Viral infection and its evolution, particularly related with infection by HIV-2, will be presented later, in the light of our experience, obtained over several years work with African people infected by the virus. The AIDS viruses are complex retroviruses, with their own identity, but also with marked structural and biological resemblances to other retroviruses, equally pathogenical for animals. The lentivirinae subfamily to which the AIDS viruses belong includes other agents, usually classified according to the host they infect. In this way, the lentiviruses of the primates contain in the same group, besides those of HIV-1 and HIV-2, viruses that infect monkeys such as SIVMAC, SIVAGM, SIVSMM, etc. The comparative study of molecular genetics and biology of human and animal retroviruses in recent years has permitted significant progress in the understanding of the possible mechanisms that lead to the Immunodepressive Acquired Syndrome that characterizes AIDS. The presence of a gene that deactivates the activated lymphocytes only present in the lentiviruses of the primates, as well as the known tropism of those viruses to CD4 lymphocytes, and not found in the other groups, are biological aspects that are pointed out. We also refer to other characteristics of HIVs such as the cytolytic and sincicial capacity of these viruses in lymphocyte culture. Finally we present an analysis of what we were able to observe in individuals infected by HIV-2 in their own and African habitat.
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PMID:[Immunodeficiency viruses]. 180 35

In view of its unique ability to stimulate human B cells, we have considered using Brucella abortus (BA) as a carrier for human vaccines. Recently we showed that HIV-1 coupled to BA, but not unconjugated HIV-1, was able to stimulate murine responses even in the relative absence of CD4+ T cells. This result suggested that HIV-BA may be useful in boosting the immunity of individuals infected with HIV-1 and who have impaired CD4+ T cell function. In order to refine this carrier we purified lipopolysaccharide (LPS) from BA and examined its effects on immune responses. Similar to LPS from E. coli (LPS-EC), LPS-BA was capable of stimulating mouse B cells to proliferate. In addition, LPS-BA could activate mouse spleen cells to secrete antibodies in vitro. Isotype analysis revealed that IgM and all the IgG subclasses were elicited. When comparing these responses to those of LPS-EC, LPS-BA induced a greater percentage of IgG2a and LPS-EC evoked more IgG3. IgG2a is probably important in protection against murine viral infection. LPS-BA was haptenated with trinitrophenol TNP-LPS (BA) and tested for carrier effect. Similar to TNP-BA and TNP-LPS (EC), TNP-LPS (BA) triggered anti-TNP antibody of the IgM and all IgG subclasses. In contrast, TNP-ficoll induced mainly IgM and only small amounts of IgG3. These results suggest that LPS-BA, like intact BA, behaves as a T-independent type 1 carrier, and as such may be advantageous as a carrier for human vaccines development.
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PMID:Immunogenicity of lipopolysaccharide derived from Brucella abortus: potential as a carrier in development of vaccines for AIDS. 180 68

A number of oligonucleotide analogues containing internucleoside phosphorothioate linkages and a covalently attached cholesteryl residue was synthesized and tested for activity against HIV-1 in cultures of Molt3 cells. Structural features important for high antiviral activity are the presence of a cholesteryl moiety, a run of terminal phosphorothioate groups, and the presence of nucleoside residues. An increase in length of the tether between cholesteryl and phosphorus from six to 14 atoms has no significant effect on antiviral activity, and up to one-half of the internucleoside links in a cholesteryl-conjugated phosphorothioate oligomer and one-third of the internucleoside links in a nonconjugated phosphorothioate can be replaced with phosphodiester links without much change in antiviral activity. However, replacement of nucleoside units in the oligomers by a simple analogue (-OCH2CH2CH2O-) yields inactive or very weakly active compounds, even in the presence of a cholesteryl group. Dose-response patterns for assays in which cholesteryl-conjugated oligomers are added to test cells either simultaneously or subsequently to viral infection are similar for homooligomer derivatives and for oligomers containing "antisense" sequences, suggesting a similarity in mode of action for the two classes of oligomers in this system.
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PMID:Effect of structural variations in cholesteryl-conjugated oligonucleotides on inhibitory activity toward HIV-1. 180 39

The intermediate filament (IF) subunit protein vimentin is efficiently cleaved in vitro by purified human immunodeficiency virus type 1 (HIV-1) protease. Immunological data confirm that identical sites are cleaved when vimentin is polymerized into filaments or occurs as protofilaments. Preformed filaments require 10 times more protease to achieve the same extent of cleavage seen with protofilaments, suggesting that the cleavage sites are partially masked in IFs. The primary cleavage gives rise to molecule lacking most of the tail domain and which not only remains in preformed filaments, but also is capable of polymerizing into essentially normal 10 nm filaments. However, these filaments of the vimentin primary cleavage product show a propensity to form large lateral aggregates. The three secondary cleavage products of vimentin additionally lack portions of the head domain, are almost quantitatively released from preformed filaments and are not capable of forming filaments de novo. These results confirm and extend previous data obtained with desmin and provide a limit for that portion of the tail domain of type III IF subunit proteins that play a role in IF formation and stability. Microinjection of HIV-1 protease into cultured human skin fibroblasts resulted in a large increase in the percentage of cells with an altered and abnormal distribution of vimentin IFs. Most commonly, the IFs were observed to have collapsed into a clump with a juxtanuclear localization. The efficient cleavage of vimentin observed in vitro and the ability of microinjected HIV-1 protease to alter IF distribution in vivo suggest that IF proteins may serve as substrates within HIV-1 infected cells and may play a role in viral infection.
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PMID:Effect of human immunodeficiency virus type 1 protease on the intermediate filament subunit protein vimentin: cleavage, in vitro assembly and altered distribution of filaments in vivo following microinjection of protease. 181 Dec 47


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