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

Human immunodeficiency viruses (HIV) isolated from infected individuals show tremendous genetic and biologic diversity. To delineate the genetic determinants underlying specific biologic characteristics, such as rate of replication, cytopathic effects, and ability to infect macrophages and T4 lymphoid cells, generation of hybrid HIV using viruses which exhibit distinct biologic features is essential. To develop methods for generating hybrid HIV, we constructed truncated HIV proviral DNA plasmids. Upon digestion with restriction enzymes, these plasmid DNAs were cotransfected into human rhabdomyosarcoma cells to generate hybrid HIV. The hybrid HIVs derived by this method were infectious upon transmission to both phytohemagglutinin-stimulated peripheral blood lymphocytes and established human leukemic T-cell lines. The virus derived from molecular clone pHXB2 (HIVHTLV-III) productively infected CEMx174 cells. On the other hand, molecular clone pARV (HIVSF2)-derived virus did not show productive infection of CEMx174 cells when used as a cell-free virus. The hybrid HIV containing the 3' end of the genome from pARV and the 5' end of the genome from pHXB2 was effective in infecting CEMx174 cells, but the converse hybrid containing 5' pARV and 3' pHXB2 was not effective in infecting CEMx174 cells. These results suggest that differences in the genes outside of env and nef play a role in the ability of the virus to infect a certain cell type. The intracellular ligation method should be useful in the analysis of related and unrelated HIV-1 isolates with common restriction enzyme cleavage sites.
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PMID:Generation of hybrid human immunodeficiency virus utilizing the cotransfection method and analysis of cellular tropism. 167 38

Apparently conflicting results have been reported regarding the role of env glycoprotein glycans in human immunodeficiency virus type 1 (HIV-1) infectivity and cytopathogenicity. Whereas we have shown that enzymic removal of carbohydrates from mature envelope glycoproteins has only limited effect on the ability of HIV-1 to bind to CD4 and to infect target cells, sugar analogues that interfere with the glycosylation process of the nascent molecule markedly reduce virus infectivity. Here we have investigated the effect of a glucosidase inhibitor, 1-deoxynojirimycin (dNM), on the bioactivity and immunoreactivity of precursor gp160 produced by recombinant vaccinia virus-infected BHK-21 cells (rgp160). dNM (4 mM) did not affect the amount of rgp160 recovered nor its secretion from the cells. As described by other authors the effect of dNM was incomplete, resulting in the production of rgp160, the glycosylation of which was heterogeneous with respect to apparent Mr distribution and to sensitivity to endoglycosidase H and endoglycosidase F, all the species being susceptible to N-glycanase. A major reduction of the binding to CD4+ cells was noted with rgp 160 produced by dNM-treated cells using a quantitative indirect immunofluorescence assay and labelling with polyclonal human anti-HIV IgG. Similarly, dNM treatment altered the accessibility to murine monoclonal antibody 110-4 of the exposed V3 loop of HIV-1 gp120 by at least 10-fold, as determined by either ELISA capture assay or immunoaffinity purification. Such bioactivity and conformation modifications, which result from the abnormal folding of the nascent glycoprotein due to aberrant glycosylation, may account for the impaired HIV-1 infectivity elicited by dNM.
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PMID:Effect of a glucosidase inhibitor on the bioactivity and immunoreactivity of human immunodeficiency virus type 1 envelope glycoprotein. 167 78

We present data on the distribution of human immunodeficiency virus (HIV-1) proviral DNA in different subsets of peripheral blood mononuclear cells (PBMCs) over an observation period of eight months. Eleven patients with well documented HIV-1 infection were studied. The PBMCs were obtained at two intervals and purified by fluorescence-activated cell sorting (FACS) after staining with FITC-labelled monoclonal antibodies. Varying numbers of FACS-sorted CD4+ cells, CD8+ cells and peripheral monocytes were assayed for HIV-1 proviral DNA (env and gag region) by PCR. Samples from patients at CDC stages II or III had to contain 10(3)-10(4) cells in order to allow detection of proviral HIV-1 DNA. At CDC stage IV, however, HIV-1 DNA was detected in as few as 100 CD4+ T-lymphocytes. In contrast, in peripheral monocytes HIV-1 DNA was not regularly found. CD8+ cells did not harbor detectable amounts of proviral DNA. During an observation period of eight months, the rate of infected CD4+ T-lymphocytes increased significantly in three patients while staying constant in the remaining eight patients. This increase of the infection rate was paralleled by clinical progression in one patient and by a decrease of the absolute number of CD4+ cells in another patient. The percentage of CD4+ cells harboring the viral genome increases in the course of the disease. These results may help to explain the decrease in CD4+ T-lymphocyte counts during HIV-1 infection.
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PMID:Progression of HIV-1 infection. Monitoring of HIV-1 DNA in peripheral blood mononuclear cells by PCR. 168 31

We investigated sequence variation in the human immunodeficiency virus type 1 (HIV-1) env gene region that encodes the fourth disulfide-bonded domain of the external membrane glycoprotein, gp120, among three HIV-1 isolates from patients with AIDS-related neurologic disease. The sequences of HIV-1 isolated directly from brain tissue, blood cells, and in vitro cell cultures were compared. The results suggest that there may be many closely related HIV-1 genomes of several distinct subtypes in an HIV-1-infected individual. Differences were observed in the frequency distribution of sequence variants obtained from brain versus blood of the same individuals. Overall, the proportion of silent mutations is much lower than expected by random occurrence. Taken together, these results favor the possibility that selective forces may play a role in the tissue distribution of certain HIV-1 strains.
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PMID:HIV-1 env sequence variation in brain tissue of patients with AIDS-related neurologic disease. 168 85

Profiles of CD8+CD11+ T suppressor cells, human immunodeficiency virus (HIV)-env-specific cytotoxic T-lymphocyte (CTL) activities, and natural killer (NK) cell activity were studied in 12 asymptomatic untreated HIV-infected patients. These patients were followed for 4-7 months. NK activity, HIV-env-specific CTL activities mediated by CD4+, CD8+ T cells and CD8+CD11+ T-suppressor cell number remained stable in seven patients during the study period. Alternatively, NK and HIV-specific CTL activities decreased and CD8+CD11+ cell number increased in five patients whose CD4+ T-cell number fell, and in four of these five patients serum p24 antigen level increased, and they developed minor clinical signs of disease progression during the study period. CD8+CD11+ cells are present in higher percentage (10-45% of peripheral blood mononuclear cells) in these HIV-infected patients as compared to those in normal individuals (3-5%). Our results suggest that CD8+CD11+ cells, NK, and HIV-specific cytotoxic activities may be helpful in monitoring prognosis of HIV infection. These observations also suggest that CD8+CD11+ cells may play an important role in the failure of host immune defences against HIV.
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PMID:Inverse relationship of CD8+CD11+ suppressor T cells with human immunodeficiency virus (HIV)-specific cellular cytotoxicity and natural killer cell activity in HIV infection. 168 22

Based on the published sequences of human immunodeficiency virus (HIV-1) isolates highly conserved regions of the gag and env genes containing immunodominant epitopes were selected and expressed in E. coli. The expression vectors pKK24 and pEX41 produced viral proteins recognized by sera obtained from HIV-1 seropositive individuals. A testing system was designed to determine the practical value of bacterially synthesized proteins of HIV-1 gag and env genes for serodiagnosis of HIV-1 infection.
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PMID:Recombinant proteins derived from immunodominant regions of the gag and env genes of HIV-1 and their potential for use in serologic diagnosis. 168 63

Three cell clones producing large numbers of infectious or noninfectious particles of human immunodeficiency virus type 1 (HIV-1), designated M 10/LAV-2, M 16/LAV-3, and MT/LAV-17, were isolated from persistently HIV-1-infected MT-4 cells. In M 10/LAV-2, the HIV-1 proteins were defective in the cleavage of gag precursor protein, and the particles were doughnut-shaped with a double-ring structure. These particles were produced by budding at the cell surface from crescentic structures followed by the formation of double-ring structures. The viral proteins in M 16/LAV-3 were defective in the cleavage of env precursor protein. The morphology of the virus particles was intact, and an electron dense bar-shaped core was seen inside a single-ring enveloped structure. The intact particles were released from the cell surface by a budding process in which crescent shape structures first appeared at the cell membrane, then subsequently just before release matured to a complete structure with an electron dense core. In MT/LAV-17, the synthesis of HIV-1 proteins was normal, and the particles were teardrop-shaped with an intact core structure. These particles were produced by budding with an electron dense core at the cell surface. Thus, it was suggested that the morphological maturation of HIV-1 particles was completed just before release from the cell surface in several cell clones producing HIV-1 particles of different morphology.
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PMID:The budding of defective human immunodeficiency virus type 1 (HIV-1) particles from cell clones persistently infected with HIV-1. 169 24

Adult C57BL/10 mice (H-2b Fv-1b) inoculated with LP-BM5 murine leukemia virus develop a disease which has many features in common with human acquired immunodeficiency syndrome (AIDS), in particular abnormal lymphoproliferation and severe immunodeficiency. In the present study, we examined the possibility that this murine AIDS (MAIDS) model would be useful for evaluating antiretrovirus drugs in vivo through the use of a well-defined antiretrovirus drug, the reverse transcriptase (RT) inhibitor (H. Mitsuya, K.J. Weinhold, P.A. Furman, M.H. St. Claire, S. Nusinoff-Lehrman, R.C. Gallo, D. Bolognesi, D.W. Barry, and S. Broder, Proc. Natl. Acad. Sci. USA 82:7096-7100, 1985) 3'-azido-3'-deoxythymidine (AZT). We evaluated the effect of AZT treatment on de novo virus infection as well as on the induction of immunodeficiency by various parameters, including RT activity in serum, splenomegaly, proliferative responses against alloantigens and mitogens, soluble-antigen-presenting cell activity, and immunoglobulin G levels in serum. Our results demonstrated that AZT treatment of C57BL/10 mice infected with LP-BM5 murine leukemia virus efficiently prevented the induction of immunodeficiency if started at the time of virus inoculation. Starting AZT treatment 1 week later provided only a partial protective effect. Starting AZT treatment 2 weeks later was associated with suppression of RT activity in serum but no prevention of immunosuppression. This MAIDS model may allow rapid and cost-effective screening for antiretrovirus drugs targeted against retroviral functions shared between human AIDS and MAIDS, such as those encoded by gag, pol, or env.
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PMID:3'-Azido-3'-deoxythymidine prevents induction of murine acquired immunodeficiency syndrome in C57BL/10 mice infected with LP-BM5 murine leukemia viruses, a possible animal model for antiretroviral drug screening. 169 56

Direct infection of glia by human immunodeficiency virus type 1 (HIV-1) has been suggested as one of several mechanisms responsible for the severe neurologic complications observed in both neonates and adults with the acquired immunodeficiency syndrome. We have demonstrated by protein immunoblotting analysis that HIV-1 infection of human fetal glial cells isolated from the dorsal root ganglia (DRG) of the developing human peripheral nervous system results in viral gag antigen expression with little, if any, detectable env gene products. No cytopathogenicity was evident in the infected cell population. Blot hybridization analyses indicate transient expression of the HIV-1 genome with maximum levels of virus-specific RNA being observed between 2 and 3 days postinfection and decreasing below the limits of detection by 16 days postinfection. To determine whether infection of the human fetal DRG glial cell population culminates in the production and release of infectious HIV-1, cocultivation and reverse transcriptase assays were performed. Direct assay of HIV-1-infected neural cell supernatants as well as exposure of permissive SupT1 cells to these HIV-1-infected neural cell supernatants resulted in no demonstrable reverse transcriptase activity in either the HIV-1-infected DRG glial cell supernatants or the SupT1 cell supernatants. Although transmission electron microscopy analyses have suggested the absence of intracellular viral particles, highly electron-dense inclusions in the cytoplasm of HIV-1-infected DRG glial cells were observed. The nature of the intracellular cytoplasmic inclusions is under current investigation. Cumulatively, these data suggest that the interaction of HIV-1 with human fetal DRG neural cells results in transient expression of the HIV genome culminating in a nonproductive infection.
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PMID:Analysis of nonproductive human immunodeficiency virus type 1 infection of human fetal dorsal root ganglia glial cells. 169 19

Previous studies revealed that antisense oligodeoxynucleotides to specific regions of the human immunodeficiency virus-1 (HIV-1) are potent inhibitors of replication of HIV-1 in vitro (Zamecnik, P. C., Goodchild, J., Taguchi, Y., and Sarin, P. S. (1986) Proc. Natl. Acad. Sci. U. S. A. 83, 4143-4146). We now report that antisense RNA, synthesized in vitro using T7 and SP6 RNA polymerase, displayed an anti-HIV-1 effect in the HTLV-IIIB/H9 system in vitro. Treatment of HIV-1-infected H9 cells with viral env region antisense RNA encapsulated in liposomes targeted by antibodies specific for the T cell receptor molecule CD3 almost completely inhibited HIV-1 production. The viral env segment covered a part of exon II of HIV-1 tat gene. No anti-HIV activity could be detected with similarly targeted liposome-encapsulated sense env RNA or with pol RNA synthesized in either the sense or antisense orientations, or with env region antisense RNA free in solution, or encapsulated in liposomes in the absence of the targeting antibody. A semiquantitative evaluation revealed that 4000-7000 RNA molecules became cell-bound in targeted liposomes; the half-life of the intracellularly present hybridizable antisense env RNA was approximately 12 h. Western blots showed that antisense env RNA suppressed tat gene expression by approximately 90% and gp160 production by 100%. These data were confirmed by immunoprecipitation studies. Northern blots (using an env probe) demonstrated the existence of all major HIV RNA species (9.3-, 4.3-, and 2.0-kb mRNA) in HIV-infected cells treated with antisense env RNA although at a reduced level. We conclude that the antisense env RNA inhibited viral protein production at the translational level.
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PMID:Inhibition of expression of human immunodeficiency virus-1 in vitro by antibody-targeted liposomes containing antisense RNA to the env region. 169 56


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