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

Antisense RNA can inhibit the expression of messenger RNAs (mRNAs) to which they are complementary by a variety of mechanisms and might provide the basis for antiviral therapies of high selectivity. In a previous study of six retrovirally expressed antisense RNAs targeted to HIV-1IIIB, we found that two significantly reduced HIV-1IIIB replication. Here we test the degree to which this inhibitory effect tolerates the natural variation found in the nucleotide sequence of different strains of HIV-1. We show that the longer of the two inhibitory antisense RNAs (600 bases) inhibits replication of HIV strains RF, MN and SF2 to at least as great an extent as it does the homologous strain. In contrast, the shorter (71 bases) does not inhibit replication of the heterologous strains. An examination of the predicted positions of the mismatches in the duplexes formed between the IIIB antisense RNAs and the mRNAs of heterologous strains suggests that one requirement of an inhibitory antisense RNA is that it can form a perfect duplex with its target mRNA of at least some 51-64 base-pairs. Although the observations presented here are not definitive proof of this, they are reminiscent of the structural requirements deduced for the double-stranded RNA-mediated induction of interferon and the activation of interferon-induced 2', 5'-oligo(A) synthetase and protein kinase. We tested the ability of antisense RNA to inhibit HIV replication in Jurkat, CEM, U937 and HeLa-T4 cells. The level of inhibition of HIV-1IIIB replication varied according to the cell line in which it was expressed, but in all cases was significant.
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PMID:Inhibition of heterologous strains of HIV by antisense RNA. 203 96

This review suggests that infections are potent immunomodulators by causing significant alterations in one or more mediators of homeostasis and that an effective antibiosis may be a potent immunomodulator, albeit indirectly. When large numbers of microorganisms are killed, their enzymes and toxins are rapidly released and activate the immune system. The septic syndrome and the potentially progressive states of septic shock, acute respiratory distress syndrome and multiple organ system failure illustrate the biological response modulating (BRM) activity of both infection and antibiotic. Enhancement of phagocytosis and intracellular killing would be a useful immunomodulatory activity for antibiotics. Equally useful would be the capacity of the antibiotic to bind or inactivate bacterial lipopolysaccharide (LPS) to diminish monocyte release of tumour-necrosing factor (TNF) at a rate equal to or faster than the killing effect of the antibiotic on bacteria. For other types of immune deficiencies, such as are observed in HIV-positive patients with secondary bacterial, fungal and viral infections, modulation of viral receptors including HIV-R on CD4 lymphocytes accompanied by their up-regulation, enhancement of interferon (IFN) and natural killer (NK) function and inhibition of CD8 suppressor activity would be important activities. The classic example of polymyxin as an immunomodulating, albeit toxic, antibiotic offers a rational and definitive basis for the concept. In-vitro data on cefodizime, a third generation cephalosporin that achieves good tissue levels, are presented and show the ability of the intact antibiotic, as well as its immunomodulating side-chain, to down-regulate TNF and interleukin 1 (IL-1) released from human monocytes by lectin-activated lymphocytes, LPS and IFN.
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PMID:Antibiotics as biological response modifiers. 207 50

After 15 years of unsuccessful efforts, the most frequent of hepatitis non-A non-B viruses has just been identified and called hepatitis C virus (HCV). The viral genome had been sequenced by an original and direct molecular biology method before the agent could be detected serologically or at electron microscopy. HCV is a small, encapsulated RNA virus, perhaps loosely related to flaviviruses. A non-structural protein, corresponding to the virus replication enzyme, is the specific component as target for ELISA tests to detect specific anti-HCV antibodies. This serology has enabled us to confirm that HCV is the most common of NANB viruses, being responsible for 60 to 80 p. 100 of all cases of post-transfusion hepatitis. The antibodies appear belatedly: in 40 p. 100 of patients they do so during convalescence, 2 to 12 months after the serum transaminase peak of primary infection. 60 to 80 p. 100 of patients with presumed NANB hepatitis are positive for anti-HCV antibodies. The same applies to cirrhosis and cancer which, in 40 p. 100 of the cases, complicates post-NB hepatitis cirrhosis. Since March 1, 1990, screening for anti-HCV antibodies has become compulsory for all blood donors in France. The prevalence of these antibodies is 0.68. Among groups of patients at risk, prevalences are 70 p. 100 in haemophiliacs, 50-75 p. 100 in drug addicts and more than 30 p. 100 in patients under haemodialysis. Sexual transmission seems to be weak but possible; 5 p. 100 of homosexuals carry anti-HCV antibodies, and this percentage is higher in HIV positive subjects. The discovery of the hepatitis C virus coincides with the finding that interferon is effective in the treatment of NANB hepatitis, and this exceptional opportunity in the field of public health should engender specific programmes. It may now be hoped that prevention by vaccine will be available in a not too distant future.
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PMID:[Hepatitis virus C: from discovery to applications in public health]. 211

Translational effects of the RNA leader and Tat protein of human immunodeficiency virus type 1 (HIV-1) were investigated in rabbit reticulocyte lysate. Hybrid RNA species with natural or mutated HIV-1 leader fused to human interferon- gamma mRNA were produced in vitro from recombinant plasmids. HIV-1 leader RNA was found to inhibit translation through two mechanisms. A 3-fold trans-inhibition of translation was demonstrated by mixing hybrid HIV-1 leader RNA with indicator interferon mRNA. By comparison, HIV-1 leader caused a 50-fold cis-inhibition in lysate in which two trans-inhibitory factors, double-stranded RNA-dependent protein kinase and (2'-5')oligoadenylate synthetase, were suppressed. In contrast, purified HIV-1 Tat protein produced in Escherichia coli enhanced by 4-fold translation from HIV-1 leader-interferon mRNA but not from interferon mRNA lacking HIV sequences or from total poly(A)+ RNA. Translation of mRNA containing either a single base substitution in the loop of the "trans-acting responsive" sequence (TAR) or an alternative stem-loop in TAR was nevertheless stimulated by Tat. The enhancement of translation by Tat was largely due to relief of cis-inhibition, since the effect was found even in lysate in which double-stranded RNA-dependent protein kinase was inhibited with 2-aminopurine. These results suggest that translation is an important level of control in the replication cycle of HIV-1.
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PMID:Direct evidence for translational regulation by leader RNA and Tat protein of human immunodeficiency virus type 1. 212 Jul 1

The concentrations of neopterin, beta-2 microglobulin, p24 antigen, anti-p24 antibody, and alpha-interferon were determined in the sera of 25 asymptomatic anti-HIV positive patients (CDC stages II and III) over a 50 month period (38 months retrospectively and 12 months prospectively). Evaluation of the data allowed the derivation of a threshold of abnormality for both neopterin and beta-2 microglobulin. Pre-AIDS (CDC groups IVa, IVc2, IVe) developed in 6 of the 26 patients within 18 months of the first abnormal value of beta-2 microglobulin, and within 12 months of the first abnormal value of neopterin. Combining the abnormal results of neopterin, beta-2 microglobulin, p24 antigen, and alpha-interferon allows prediction of progression to pre-AIDS within 18 months for most asymptomatic patients.
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PMID:Neopterin and beta-2 microglobulin levels in asymptomatic HIV infection: the predictive value of combining markers. 212 81

In the present paper, we have studied the effects of interferon (IFN) -alpha and IFN-beta on the oxidative burst (OB) responses in monocytes and monocyte-derived macrophages from patients with a relatively early phase of HIV infection. We found that in monocytes from patients with HIV infection, the defective OB response could be partially restored by pretreatment with IFN-beta when the cells were challenged with zymosan. No such stimulatory effect was seen in the control groups. In monocyte-derived macrophages, both IFN-alpha and IFN-beta stimulated the phorbol myristate acetate (PMA) induced OB response in the patient group as well as in the blood donor control group. Generation of an OB is an important part of the antimicrobial defence of mononuclear phagocytes. The positive effects of IFN on the OB responses of monocytes and macrophages from patients with HIV infection may be of importance when IFNs are considered in the treatment of HIV-related disease.
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PMID:Effects of alpha- and beta-interferon on oxidative burst responses of monocytes and monocyte-derived macrophages from patients with HIV infection. 213 79

Natural killer (NK) cells may be of significance in host defense against viral infections. In the present study, NK cell function was examined in relation to different phases of human immunodeficiency virus (HIV) infection. Peripheral blood mononuclear cells were tested for NK cell activity using K562 cell targets in a 51Cr-release assay. NK cell responses of 26 HIV-seronegative homosexual men were not significantly different from those of 30 heterosexual controls. NK activity was significantly lower in cells from 32 homosexual men with documented, early-phase HIV infection (average of 14 months; range of 3-27 months) as compared with that of seronegative men. The NK cell response decreased with time, since men within the first year of infection (n = 15; average of 7.8 months; range of 3-12 months) had greater NK cell activity than did those with longer duration of infection (n = 17; average of 18.3 months; range of 13-27 months). The decrease in NK cell activity did not correlate with altered numbers of cells bearing CD16 (NK) markers in these subjects. NK cell-mediated lysis and cell numbers were most severely depressed in a separate group of HIV-seropositive men who had acquired immune deficiency syndrome (AIDS). In vitro treatment with alpha-interferon (alpha-IFN) significantly enhanced NK activity of effector cells obtained from men within the first year of HIV infection but not in those with longer-term infection. Our results indicate that NK cell function decreases over time within the first 2 years of HIV infection in homosexual men, and is lowest in HIV-seropositive men with overt AIDS.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Natural killer cell responses in homosexual men with early HIV infection. 214 Oct 73

We report that 11 human immunodeficiency virus 1 (HIV-1)-seropositive patients, including three AIDS patients, were able to generate a cellular immune response to the intradermal injection of low doses (2-10 micrograms) of recombinant interleukin 2 (rIL-2). A dose-dependent zone of induration appeared at the site of injection, peaked at 24 hr, and was accompanied by the local accumulation of T cells, monocytes, and Langerhans cells. Despite the reductions in the CD4+ T-cell counts in the peripheral blood of most patients, CD4+ T-cells could still be mobilized with rIL-2 injections into the skin. The total number of immigrant cells was equivalent to those in HIV-1-seronegative patients, although the CD4+/CD8+ ratio of the dermal population was reduced. In response to rIL-2, major histocompatibility complex (MHC) class II antigen was expressed on the surface of keratinocytes, Langerhans cells, lymphocytes, and macrophages. In addition, the gamma interferon (IFN-gamma)-induced protein IP-10 rapidly appeared in dermal inflammatory cells and keratinocytes. A majority of HIV-1-seropositive patients demonstrated low or absent responses to common skin-test antigens. Those with positive zones of induration were often defective in the cellular expression of the IFN-gamma-induced MHC class II antigen. The simultaneous administration of rIL-2 and soluble antigen at widely separated cutaneous sites led to an enhancement of skin-test antigen reactivity in seropositive patients. The results suggest that local administration of rIL-2 to seropositive patients may act systemically, stimulating cellular immunity to recall antigens, and thus may be of potential benefit in the defense against opportunistic pathogens encountered in HIV-1 infection.
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PMID:Cutaneous response to recombinant interleukin 2 in human immunodeficiency virus 1-seropositive individuals. 214 21

After much frustration in the last decade, HIV therapeutics is an emerging discipline. Over the past few years a number of new agents have been evaluated, including such antiviral drugs as zidovudine, dideoxycytidine and dideoxyinosine, and immunomodulators such as alpha interferon and interleukin-2. The author discusses these and other agents and the prospects for combination therapy.
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PMID:Current and future treatment of HIV infection. 215 Mar 23

Macrophages, unlike CD4+ T cells, can be productively infected by human immunodeficiency virus (HIV) without prior cellular activation. Cytopathic infection ensues without the induction of tumor necrosis factor alpha (TNF alpha), interleukin 1 beta (IL-1 beta), interleukin 6 (IL-6), or tissue factor genes. In detailed studies on TNF alpha, HIV infection did not affect the regulation of TNF alpha in response to bacterial lipopolysaccharide. In an effort to examine the interferon responsiveness of HIV-infected macrophages, the cells were challenged with vesicular stomatitis virus (VSV) with or without interferon pretreatment. Surprisingly, HIV-infected macrophages were completely resistant to VSV-induced lysis even in the absence of interferon; however, no interferon was detected in the supernatants of these infected cells. The resistance of HIV-infected macrophages to superinfection with VSV indicates a previously undescribed effect of HIV upon macrophage cellular metabolism.
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PMID:Characterization of a macrophage-tropic HIV strain that does not alter macrophage cytokine production yet protects macrophages from superinfection by vesicular stomatitis virus. 217 98


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