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Enzyme
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Target Concepts:
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Query: UMLS:C0019693 (
HIV
)
170,526
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Prevalence of markers of HBV infection was tested in two cohorts of drug addicts: in 140 addicts whose sera were drawn in the years 1985-1986 and in 100 addicts whose sera were drawn in the years 1988-1989. HBsAg was found in 10 (7%) patients in the earlier cohort and in 12 (12%) addicts in the latter, while at least one marker of HBV infection was present in 39% and 69%, respectively No correlation was found between the presence of markers of HBV infection and age, gender, or
HIV
status, however, duration of drug abuse increased the risk of HBV infection. There was no difference in mean titres of anti-CMV and anti-HSV-1 between subjects with and without HBV markers what suggests that the tested markers were specific.
Pol
Arch Med Wewn 1992 Feb
PMID:[Markers of HBV infection in drug addicts]. 152 36
The protease from simian immunodeficiency virus (SIV) was chemically synthesized by automated solid-phase technology as an NH2-terminally extended derivative, capped with biotin. Biotin-linker-(SIV protease (1-99)): the linker segment, Gly-Gly-Asp-Arg-Gly-Phe-Ala-Ala, corresponds to the amino acid sequence preceding that of the protease in the SIV gag/
pol precursor
polyprotein. Accordingly, the Ala-Pro bond joining the octapeptide linker to the protease constitutes a site naturally cleaved by the protease during viral maturation. This strategy for synthesis was designed to facilitate purification of the biotinylated protein derivative from a complex mixture of reaction products by avidin/agarose-affinity chromatography and to provide the means for autocatalytic removal of the biotin-linker segment. As anticipated, folding of the full-length construct leads to activation of the enzyme and excision of the desired 99-residue SIV protease (overall yield, approximately). The specificity of the synthetic SIV protease toward a number of well characterized protein substrates was the same as observed for the nearly identical enzyme from human immunodeficiency virus type 2 (HIV-2 protease) and distinct from that of the more disparate HIV-1 protease. The same functional ordering with respect to the human retroviral proteases was reflected in Ki values observed with a number of protease inhibitors. Thus, the folded synthetic SIV protease shows patterns of specificity and susceptibility to inhibition that are in accord with what would be expected based upon its degree of structural similarity to proteases from
HIV
-1 and
HIV
-2.
...
PMID:Chemical synthesis of a biotinylated derivative of the simian immunodeficiency virus protease. Purification by avidin affinity chromatography and autocatalytic activation. 158 12
HIV
-1 proteinase activity is thought to occur primarily post-integration by cleaving the viral Gag and Gag-
Pol
polyproteins. Its role in the pre-integration stages of viral replication, however, has not been studied in detail. Here we report that a synthetic peptide analogue, UK-88,947, which is a specific inhibitor of purified
HIV
-1 proteinase, inhibits the processing of the viral polyproteins in cultures of
HIV
-1 infected cells and prevents the formation of mature, infectious virions. Analysis of DNA from
HIV
-1 infected cells treated with UK-88,947 showed that viral DNA synthesis was inhibited when the compound was added to cultures one hour before infection. Similar results were obtained when AZT was used. Neither
HIV
-1 reverse transcriptase or the replication of FIV are inhibited by UK-88,947.
...
PMID:HIV-1 proteinase is required for synthesis of pro-viral DNA. 165 47
250 determinations of lymphocyte T subsets in 130
HIV
infected patients (79 asymptomatic carriers or with lymphadenopathy, 31 ARC- and 20 AIDS-patients) were analyzed as to the percentage, number, and ratio of T4 (helper) and T8 (cytotoxic/suppressor) lymphocytes in sequential clinical stages of
HIV infection
. Asymptomatic
HIV
carriers or patients with lymphadenopathy were found to have statistically significant higher counts of erythrocytes, platelets, total lymphocytes, percentage and number of T4 lymphocytes and T4/T8 lymphocyte ratio than the ARC-patients. Persons with ARC in comparison with AIDS-patients were found to have significantly higher values of erythrocytes, platelets, leucocytes, total lymphocytes, T4 lymphocytes, percentage and count of T8 lymphocytes and T4/T8 lymphocyte ratio. In AIDS patients a statistically significant correlation was seen between number of T4 lymphocyte and number of erythrocytes, platelets, total number of lymphocytes and value of T4/T8 lymphocyte ratio.
Pol
Arch Med Wewn 1991 Oct
PMID:[T4 lymphocytes (helper cells) and T8 lymphocytes (cytotoxic and suppressor cells) in patients with asymptomatic and symptomatic HIV infection]. 168 8
Sequential changes of percentage and number of T4 (helper) and T8 (cytotoxic/suppressor) lymphocyte subsets and serum beta 2 microglobulin (beta 2m) level were observed in 23
HIV
infected patients for a period of 4 months to 3 years. 10 subjects were asymptomatic
HIV
carriers, 9 had already AIDS at the beginning of the study and 4 patients developed clinically overt disease during the observation period. T4 lymphocyte number remained in normal range in asymptomatic
HIV
carriers but in 4 patients its decrease preceded the development of clinical symptoms of infection. A rapid decrease of T4 lymphocyte number was generally observed in AIDS patients. Serum concentration of beta 2m remained at relatively low and constant level in asymptomatic
HIV
carriers but in 4 cases its increase preceded the appearance of clinical symptoms. In patients with clinically overt disease beta 2m levels were significantly increased and reached the highest values just before death. A correlation between clinical stage of infection and the number of T4 lymphocytes and beta 2 m level was found.
Pol
Arch Med Wewn 1991 Oct
PMID:[Prospective studies of T4 and T8 lymphocyte subpopulations and beta 2-microglobulin in patients with HIV infection]. 168 9
The influence of glucocorticosteroids (GKS) therapy on clinical status, T4 lymphocyte count in peripheral blood and T4/T8 lymphocyte ratio was investigated in five
HIV
infected patients: two were asymptomatic, while three had clinically overt disease. The reasons for GKS therapy were: thrombocytopenia in two patients, pancytopenia in two and sepsis with severe endocarditis in one. No influence of GKS on the clinical course of
HIV infection
was observed. The prospective determinations of T4 lymphocyte count and T4/T8 lymphocyte ratio were relatively constant in two cases, in one case increased and in two patients, one of whom had AIDS, a decrease in both parameters was observed. It seems that GKS therapy does not seriously influence the course of
HIV infection
in most patients and can be instituted without risk of severe worsening of the immune status.
Pol
Arch Med Wewn 1991 Dec
PMID:[Influence of therapy with glucocorticosteroids on clinical status, t4 lymphocyte count and t4/t8 lymphocyte ratio in people infected with AIDS]. 168 96
A total of 74 serum samples from 37 AIDS patients were analysed for
HIV
antigen and results were correlated with duration of the disease, predominant symptoms, T4 lymphocyte count in peripheral blood, and antiviral therapy. The prevalence of
HIV
-Ag increased with duration of AIDS and T4 lymphocyte depletion. It was also higher in patients who were not treated with antiviral therapy than in treated persons. No correlation was found between
HIV
-Ag and clinical picture of AIDS.
HIV
antigenemia indicates a poor prognosis and can be regarded as an additional parameter of monitoring of AIDS patients.
Pol
Arch Med Wewn 1991 Dec
PMID:[Occurrence of HIV antigens in patients with acquired immunodeficiency syndrome]. 168 97
Retroviruses encode proteinases necessary for the proteolytic processing of the viral gag and gag-
pol precursor
proteins. These enzymes have been shown to be structurally and functionally related to aspartyl proteinases such as pepsin and renin. Cerulenin is a naturally occurring antibiotic, commonly used as an inhibitor of fatty acid synthesis. Cerulenin has been observed to inhibit production of Rous sarcoma virus and murine leukaemia virus by infected cells, possibly by interfering with proteolytic processing of viral precursor proteins. We show here that cerulenin inhibits the action of the
HIV
-1 proteinase in vitro, using 3 substrates: a synthetic heptapeptide (SQNYPIV) which corresponds to the sequence at the
HIV
-1 gag p17/p24 junction, a bacterially expressed gag precursor, and purified 66 kDa reverse transcriptase. Inhibition of cleavage by
HIV
-1 proteinase required preincubation with cerulenin. Cerulenin also inactivates endothiapepsin, a well-characterised fungal aspartyl proteinase, suggesting that the action of cerulenin is a function of the common active site structure of the retroviral and aspartic proteinases. Molecular modelling suggests that cerulenin possesses several of the necessary structural features of an inhibitor of aspartyl proteinases and retroviral proteinases. Although cerulenin itself is cytotoxic and inappropriate for clinical use, it may provide leads for the rational design of inhibitors of the HIV proteinase which could have application in the chemotherapy of AIDS.
...
PMID:In vitro inhibition of HIV-1 proteinase by cerulenin. 169 Jan 52
The genome of human immunodeficiency virus type 1 (HIV-1) encodes at least six proteins involved in regulation as well as the structural proteins Gag,
Pol
, and Env. The interplay of the various regulators generates early and late transcriptional phases in the
HIV
-1 life cycle; the earliest RNA is enriched in subgenomic species, and the genomic transcript appears at the later stage of infection. We investigated the nature of the mRNAs expressed in the early stages of infection when the 2 kilobase subgenomic species predominate. RNA was analyzed in the early phase of a one-step growth cycle of
HIV
-1 infection in T-lymphoid and monocytic cell lines by using PCR amplification of in vitro-synthesized viral cDNAs. In both cell lines, expression of Tat-, Rev-, and Nef-specific messages appeared simultaneously and could be detected within 8-12 hr of infection but in different amounts with a predominance of Nef-specific message. The Env-specific message could be detected as early as the Rev-specific message, indicating that expression of at least small amounts of the singly spliced message could occur before the accumulation of Rev.
...
PMID:Kinetics of expression of multiply spliced RNA in early human immunodeficiency virus type 1 infection of lymphocytes and monocytes. 173
The expression of Gag,
Pol
, Vif, Vpr, Vpu, and Env proteins from unspliced and partially spliced human immunodeficiency virus type 1 (HIV-1) mRNAs depends on the viral protein Rev, while the production of Tat, Rev, and Nef from multiply spliced mRNAs does not require Rev. To investigate the difference between gag and tat mRNAs, we generated plasmids expressing tat-gag hybrid mRNAs. Insertion of the gag gene downstream of the tat open reading frame in the tat cDNA resulted in the inhibition of Tat production. This inhibition was caused, at least in part, by a decrease in the stability of the produced mRNA. Deletions in gag defined a 218-nucleotide inhibitory sequence named INS-1 and located at the 5' end of the gag gene. Further experiments indicated the presence of more than one inhibitory sequence in the gag-protease gene region of the viral genome. The inhibitory effect of INS-1 was counteracted by the positive effect mediated by the Rev-Rev-responsive element interaction, indicating that this sequence is important for Rev-regulated gag expression. The INS-1 sequence did not contain any known
HIV
-1 splice sites and acted independently of splicing. It was found to have an unusually high AU content (61.5% AU), a common feature among cellular mRNAs with short half-lives. These results suggest that
HIV
-1 and possibly other lentiviruses have evolved to express unstable mRNAs which require additional regulatory factors for their expression. This strategy may offer the virus several advantages, including the ability to enter a state of low or latent expression in the host.
...
PMID:Distinct RNA sequences in the gag region of human immunodeficiency virus type 1 decrease RNA stability and inhibit expression in the absence of Rev protein. 172 77
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