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Query: UMLS:C0001175 (AIDS)
 120,706 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The HIV viral burden and RNA expression in a selected group of infected, clinically non-progressor patients were investigated. Five fast-progressor patients and 10 AIDS cases were included as controls. The HIV viral load was investigated by semiquantitative polymerase chain reaction (PCR) in adherent macrophages and in genomic and extragenomic fractions of lymphocytes. HIV DNA was not found in macrophages in the non-progressor subjects, was weakly positive in 2 of 5 fast-progressors and strongly positive in most of the AIDS patients. The number of HIV proviruses found in lymphocytes of the non-progressor subjects varied from 5 to 160 copies/microgram DNA, values ten times lower than those recorded in fast-progressors and AIDS patients. The extragenomic HIV DNA (2 LTR forms) was absent or barely detectable in the lymphocytes from non-progressors and abundant in the other groups. HIV RNA was not found in the lymphocytes of all non-progressors. This may indicate that a latent state of HIV provirus exists in the lymphocytes of these subjects. To investigate this point, cultivation and stimulation with PHA (phytohemoagglutinin) and PMA (phorbol 12-myristate 13-acetate) of lymphocytes from these subjects were attempted but after 6 days HIV RNA (RT-PCR for gag region) was still absent or barely detectable in these patients. There are no other reports of the absence of HIV provirus induction in lymphocytes from infected individuals. If confirmed in a larger number of patients, such non-inducibility might serve as a predictor marker of progression of the disease.
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PMID:Peripheral lymphocytes of clinically non-progressor patients harbor inactive and uninducible HIV proviruses. 763 97

Rhesus monkeys were inoculated with SIVDeltaB670 and sacrificed 2, 4, 8, and 24 weeks after inoculation or when moribund. Two monkeys predicted to have a rapid disease course and two predicted to have a slower disease course were sacrificed at each time point. Lymph nodes were studied by histopathology, immunohistochemistry, in situ hybridization, electron microscopy, flow cytometry for lymphocyte subsets, and mitogen responsiveness. A greater selective decrease in peripheral CD4+CD29+ (helper-inducer/memory) T cells occurred in monkeys with high antigenemia. Although the percentage of CD8+ lymphocytes was increased and the CD4+/CD8+ ratio decreased in all infected groups, there were no consistent differences between monkeys with high or low antigenemia in lymph node lymphocyte subsets. Blastogenic responses of lymph node lymphocytes to PHA, ConA, or PWM were not significantly altered in infected monkeys. A reticular pattern typical of antigen deposition within germinal center follicular dendritic cells was seen in three monkeys with atrophic lymph nodes, high serum antigenemia, and a low percentage of circulating CD4+/CD29+ cells. More individually stained cells were in monkeys with high serum antigen and in moribund animals. By in situ hybridization, most monkeys had signal in a reticular pattern of germinal centers. Animals with higher levels of serum antigenemia tended to have more infected cells and a more intense signal. Extracellular virions were found between the FDC foot processes in the germinal centers of lymph nodes. Disease course was already established 2 weeks after inoculation.
AIDS Res Hum Retroviruses 1995 Feb
PMID:Distribution of SIV in lymph nodes of serially sacrificed rhesus monkeys. 774 41

Protein Kinase C (PKC) and Ca++ are both involved in the chain of events leading to T-cell activation. An impairment of the immune response is characteristic of T cells obtained from patients with HIV infection. In this report, the involvement of PKC and Ca++ in HIV-mediated cellular hyporesponsiveness was examined. Infection of peripheral blood mononuclear cells (PBMC)s from HIV-seronegative normal donors with HIV strain HTLV IIIB, or two fresh patient isolates produced a 1.4-, 10.7-, and 11.4-fold enhancement in PKC activity at 1 hr postinfection (PI) and a 1.8-, 2.3-, and 3.8-fold enhancement at 12 hr PI, respectively. A marked decrease of PKC content, as determined by Western Blot analysis, was observed in HIV-infected cells by Day 4 and 7 PI compared with mock-infected control cells. Furthermore, PKC synthesis was also inhibited in cells from immunosuppressed AIDS patients. PKC activity of PBMCs from HIV-infected patients did not change in response to 1 microM of phorbal myristate acetate (PMA). In contrast, the same dose enhanced the activity by 50%-100% in PBMCs from normal HIV-seronegative donors. A 40%, 50%, and 125% increase in intracellular free Ca++ in response to HIV infection was observed 12 hr PI in MT4, JURKAT, and PBMCs, respectively. However, the increase in intracellular free Ca++ in HIV-infected PBMCs obtained from normal donors in response to PHA was 56% and 17% compared with an increase of 100% and 120% in mock infected cells at 12 hr and 1 week PI, respectively. Comparing the Ca++ response to PHA in PBMCs from HIV-infected patients showed that patients with < 250 absolute T4 cells/mm3 had an impaired Ca++ response. These data suggest that there is a relationship between intracellular free Ca++ and PKC and HIV-induced T-cell hyporesponsiveness.
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PMID:Protein kinase C and intracellular free Ca++: relationship to human immunodeficiency virus (HIV)-induced cellular hyporesponsiveness. 780 Jun 84

Positively charged amino acid substitutions at positions 11 and 25 within the loop of the third variable region (V3) of HIV-1 subtype B envelope have been shown to be associated with the syncytium-inducing (SI) phenotype of the virus. The present study was designed to examine SI and NSI-associated V3 mutations in HIV-1 subtypes other than B. HIV-1 RNA was isolated from 53 virus stocks and 26 homologous plasma samples from 53 recently infected individuals from Brazil, Rwanda, Thailand, and Uganda. The C2-V3 region of the viral envelope was converted to cDNA, amplified, and sequenced. Of 53 primary virus stock samples 49 were biologically phenotyped through measurement of the syncytium-inducing capacity in MT-2 cells (to differentiate between SI and NSI phenotypes). In addition, after passage of primary isolates through PHA stimulated donor PBMC, the replication capacity was determined in U937-2, CEM, MT-2, and Jurkat-tat cell lines (to differentiate rapid/high and slow/low phenotypes). According to the sequence analysis 9 (17.0%) of the viruses belonged to subtype A, 15 (28.3%) to subtype B, 1 (1.9%) to subtype C, 13 (24.5%) to subtype D, and 15 (28.3%) to subtype E. Sequence analysis of virus RNA, obtained from 26 homologous plasma samples, confirmed the homogeneity of sequence populations in plasma compared to primary virus isolates. Of the 49 viruses tested 12 had the SI phenotype, 5 were confirmed to be rapid/high, and 4 appeared to be slow/low pattern 3 replicating. Of 49, 29 had the NSI phenotype, 24 were confirmed to be slow/low pattern 1 or 2, and 3 appeared to be slow/low pattern 3 replicating. Analysis of mutations at V3 loop amino acid positions 11 and 25 revealed that 10/12 (83.3%) of the SI viruses had SI-associated V3 mutations and that 28/29 (96.6%) of the NSI viruses lacked these mutations. V3 loop heterogeneity, length polymorphism, and a high number of positively charged amino acid substitutions were most frequently found among subtype D variants. These results indicate that both the phenotypic distinction between SI and NSI viruses and the association of biological phenotype with V3 mutations is present among HIV-1 subtypes other than B.
AIDS Res Hum Retroviruses 1994 Nov
PMID:Syncytium-inducing and non-syncytium-inducing capacity of human immunodeficiency virus type 1 subtypes other than B: phenotypic and genotypic characteristics. WHO Network for HIV Isolation and Characterization. 788 92

Recent evidence suggests that T cell apoptosis could be involved in the pathogenesis of HIV-1 infection. As the progression of HIV-2 associated disease appears to be slower than that of HIV-1, we investigated whether there were differences in the degree of T cell death and apoptosis in peripheral blood mononuclear cell (PBMC) cultures from patients with HIV-1 or HIV-2 infection. PBMC from healthy controls (n = 28) and patients infected with HIV-1 (n = 26: asymptomatic (ASY)/persistent generalized lymphadenopathy (PGL), n = 16; and AIDS-related complex (ARC)/AIDS n = 10) or HIV-2 (n = 30: ASY/PGL, n = 16; ARC/AIDS, n = 14) were cultured in the absence or presence of mitogens (PHA, PWM) or superantigen (SEB). After 48 h, cell death (CD) was assessed by trypan blue exclusion and in some patients programmed cell death (PCD) was quantified in flow cytometry by measuring the percentage of hypodiploid nuclei corresponding to fragmented DNA, after treating the cells with a propidium iodide hypotonic solution. HIV-1 and HIV-2 ARC/AIDS patients and ASY/PGL HIV-1+ patients had significant increases in cell death percentages compared with controls, both in unstimulated and stimulated lymphocyte cultures. However, HIV-2+ ASY/PGL patients did not exhibit significant increases of cell death in unstimulated cultures. In addition, the comparison between HIV-1 and HIV-2 infected subjects in similar stages of disease, showed no significant differences in CD in the ARC/AIDS patients, although ASY/PGL HIV-2 infected subjects had lower levels of CD than the HIV-1+ ASY/PGL (3.4% +/- 0.6 s.e.m. versus 6.8% +/- 1.1 s.e.m., P < 0.01). PCD was significantly increased both in ASY/PGL (14.3% +/- 2.2 s.e.m., n = 8, P < 0.005) and in ARC/AIDS (25.3% +/- 4.5 s.e.m., n = 9, P < 0.001) HIV-1+ patients compared with healthy controls (5.8% +/- 1.7 s.e.m., n = 11). This contrasts with HIV-2 infected subjects where the ASY/PGL patients (10.0% +/- 2.8 s.e.m., n = 6) did not differ significantly from healthy controls, although ARC/AIDS patients (27.2% +/- 4.2 s.e.m., n = 9, P < 0.001) had significantly increased levels of PCD. In conclusion, this is the first report describing the occurrence of spontaneous and activation-induced lymphocyte death by apoptosis in HIV-1 infected subjects.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Analysis of lymphocyte cell death and apoptosis in HIV-2-infected patients. 795 20

Interspecies human x mouse cell hybrids were used to investigate the genetic basis of human permissivity to HTLV-IIIB infection. T cell hybrids between the mouse BW 51.47 T lymphoma line and normal, PHA-IL-2 activated, human peripheral mononuclear cells (PBMCs) were generated. These hybrids preferentially segregated human chromosomes, as assessed by phenotype and karyotype analysis. Viral integration occurred only in those hybrids expressing CD4+ at the cell surface. However, infectious progeny production was demonstrated only in two of the three CD4+ hybrids tested. By segregation analysis, we could correlate the absence of human chromosomes 1, 3, and 9 with the lack of infectious viral progeny.
AIDS Res Hum Retroviruses 1993 Dec
PMID:Susceptibility of human-mouse T cell hybrids to HIV-productive infection. 814 44

The expression of human immunodeficiency virus type 1 (HIV-1) is enhanced after cell activation because of the interaction of cell-encoded nuclear factors that interact with binding sites in the long terminal repeats (LTRs). Here we studied the contribution of cell type-specific activation signals to differences in cytotropism of HIV-1 variants. Four closely related molecular HIV-1 clones with distinct biological phenotypes and different capacities to replicate in primary monocyte-derived macrophages (MDMs) or T cell lines were used. Sequence analysis of these LTRs revealed variation in functionally important regions. Adaptation of virus variants to particular host cells by differences in LTR responsiveness was analyzed. LTR-CAT constructs were transiently transfected in T cells that were stimulated with T cell-specific activation signals such as combinations of anti-CD3 or anti-CD28 MoAB or in primary monocytes that were stimulated with IL-3, IL-4, or GM-CSF. No differences in responsiveness to cell type-specific signals were demonstrated. To further elucidate the level of restriction in cell tropism, transfection of four full-length infectious molecular HIV-1 clones into 5-day cultured MDMs was performed. From all clones, competent virus could be rescued from MDMs by coculture with PHA-stimulated PBLs. However, following cell-free inoculation, proviral DNA could be detected by PCR analysis only in monocytes exposed to HIV-1 clones that previously were shown to establish productive infection.(ABSTRACT TRUNCATED AT 250 WORDS)
AIDS Res Hum Retroviruses 1993 Jul
PMID:Early replication steps but not cell type-specific signalling of the viral long terminal repeat determine HIV-1 monocytotropism. 836 71

Recently, as a new type of anti-AIDS drug, an HIV-1 protease inhibitor, KNI-174, has been synthesized; it shows a potent and selective HIV-1 protease inhibitory activity in vitro. In this study, we developed an HPLC assay system for KNI-174 in rat plasma and examined the pharmacokinetics of KNI-174 in rats using this assay method after both intravenous (i.v.) and intraduodenal (i.d.) administrations to obtain the disposition characteristics and bioavailability of this new anti-AIDS drug. This HPLC assay method is specific to KNI-174 and the standard curve was linear from 0.02 to 30 micrograms ml-1 plasma. After i.v. administration, 10.0 mg kg-1, KNI-174 disappeared from the rats' plasma in a three-exponential decay. The mean terminal elimination half-life, t1/2 lambda z, was 3.97 +/- 0.19 (S.E.) h, the total body clearance, CLtot, was 9.53 +/- 1.08 ml min-1 and the distribution volume at steady state, Vd,ss, was 7070 +/- 960 ml kg-1. In the case of the i.d. administration, 10.0 mg kg-1, the mean peak plasma concentration, Cmax, and the peak time, tmax, were 0.196 +/- 0.076 micrograms ml-1 and 0.444 +/- 0.193 h, respectively. The bioavailability of KNI-174 till infinity, BA(0-infinity), was 5.37 per cent. Because the IC50 of KNI-174 against HIV-1 in PHA-PBM was 138 ng ml-1, the time needed for maintaining the concentrations above IC50 after a single i.d. administration of KNI-174 is estimated to be 0.350 +/- 0.184 h.
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PMID:Pharmacokinetic study of a tripeptide HIV-1 protease inhibitor, KNI-174, in rats after intravenous and intraduodenal administrations. 849 Jan 8

The development of effective therapies for the treatment of AIDS would be facilitated by a better understanding of HIV pathogenesis in vivo. While some aspects of pathogenesis may be assessed by standard tissue culture assays, in vivo animal models may provide clues to other aspects of HIV-mediated progression toward AIDS. Current animal models include primate models for the study of simian immunodeficiency virus (SIV) and HIV, SCID-hu and hu-PBL SCID mouse models for the study of HIV, and feline models for the study of feline immunodeficiency virus (FIV). In general these models are costly and labor intensive. We have developed a simple human fetal thymic organ culture (TOC) system that is permissive for HIV infection and that exhibits pathology similar to that observed in vivo. A key feature of this system is the time-dependent destruction of thymocytes typified by the preferential loss of CD4-expressing cells. HIV-mediated thymocyte destruction occurs by a process involving programmed cell death. We have infected TOC with a panel of HIV isolates and found that the resulting viral replicative and pathogenic profiles are similar to those seen in the SCID-hu Thy/Liv mouse, yet different from profiles observed in standard PHA-blast tissue culture assays. In addition, we find that TOC may be used to assess efficacy of antiviral agents such as AZT (3'-azido-3'-deoxythymidine) and ddI (2',3'-dideoxyinosine) in blocking both viral replication and virus-induced pathology. These results indicate that this model is amenable to the systematic manipulation, analysis, and characterization of a variety of HIV virus isolates and antiviral therapies.
AIDS Res Hum Retroviruses 1995 Sep
PMID:Development of a human thymic organ culture model for the study of HIV pathogenesis. 855 4

We have evaluated immunologic markers of disease progression in 79 children perinatally infected with HIV. Laboratory testing included T lymphocyte subsets and lymphoproliferative responses (LPR) to mitogens (PHA, Con A, and PWM), antigens (Candida, Tetanus), and alloantigens (MLC). Patients were graded into grades I, II, and III based on results of CD4 counts, and into grades A, B, and C based on results of LPR, with grades I and grades A being normal, III and C being the lowest, and II and B falling in-between. CD4 counts, CD4/CD8 ratio, and lymphoproliferative responses were markedly decreased in a majority of children. Grade III CD4 counts were almost always associated with decreased LPR. A majority of the children with grade I CD4 numbers, however, also had abnormal lymphoproliferative responses. Results of laboratory testing were analyzed in relation to clinical disease progression and survival. The first AIDS defining illnesses (ADI), especially opportunistic infections (OI), was usually associated with Grade III/C results in immunologic assays. Survival was significantly decreased in children with grade III CD4 cell counts, and grade C LPR, and was poorest if these abnormalities developed within the first year of life. In this latter age group, if the CD4 counts fell to grade III, the risk for dying was at least five times greater than those children with higher CD4 counts (grades II and I); if the proliferative responses to PHA and MLC were in Grade C, the survival was 22 months. Severe immune defects in the first year of life in children with HIV infection, as assessed by CD4 counts and a battery of functional tests, predicted rapid disease progression.
AIDS Res Hum Retroviruses 1995 Oct
PMID:Immunological characteristics of HIV-infected children: relationship to age, CD4 counts, disease progression, and survival. 857 77


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