Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.1.30.2 (endonuclease)
18,621 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We describe here several African isolates of HIV, compare them to U.S.-European prototype isolates and to each other, correlate the number of isolates with serological results, and provide insights into the disease spectrum associated with HIV infection in Africa. Three of 25 healthy Zairian donors and 54 of 87 Zairian patients selected for specific pathology and hospitalized in the internal medicine department of the University Clinic of Kinshasa, Zaire, were HIV positive over a six month period in 1985 either by serum antibody (42 cases) or virus isolation (40 cases). The virus positive cases showed a decrease in number of T4 cells and interleukin-2 (IL2) production by mononuclear cells. Restriction endonuclease analysis of HIV sequences from these isolates showed that genomic diversity is also observed in the Zairian isolates but closely related viruses could also be found, similar to the spectrum of diversity among isolates obtained from the U.S. and Europe. A number of isolates (12 of 40) were obtained from serum antibody negative adults. These results are difficult to explain by viral antigenic diversity alone since hybridization with a HTLV-III-B (clone BH10) probe under stringent conditions indicated an overall high degree of relatedness. Rather, these results indicate that some African HIV infected patients fail to make detectable antibodies to HIV or the antibodies were bound in immune complexes not detectable by current techniques.
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PMID:Genomic diversity of Zairian HIV isolates: biological characteristics and clinical manifestation of HIV infection. 245 28

Single genotypic variants of HIV-I, contained in a parental cytopathic HIV-I isolate, were isolated by molecular cloning and propagated in susceptible cells. Two such HIV-I clones, designated N1T-E and N1T-A, exhibited similar restriction endonuclease maps but strikingly different biological activities. Infection of T lymphocytes or monocytes by clone N1T-E was characterized by slow kinetics and lack of significant cytopathic effects, but high reverse transcriptase activity levels in culture supernatants of chronically-infected cells. Clone N1T-A, like the parental HIV-I isolate, exhibited fast kinetics of infection in T cells and monocytes and strong cytopathicity in these cells. Full characterization of the low-cytopathic virus in comparison to the structurally similar cytopathic clone may facilitate the elucidation of the molecular basis of HIV cytopathogenicity.
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PMID:Low-cytopathic infectious clone of human immunodeficiency virus type I (HIV-I). 245 68

Elimination of the protease domain from the polymerase open reading frame (pol) of the human immunodeficiency virus type 1 (HIV-1) leads, in Escherichia coli, to synthesis and accumulation of a non-processed 98-kDa reverse transcriptase/endonuclease (RT/ENDO) polyprotein. A partially purified preparation of this reverse RT/ENDO polyprotein displays little or no RT activity. Introduction of the pol protease domain as a separate transcriptional unit on the same plasmid restores the processing program, generating correctly sized RT and ENDO polypeptides. Concomitant with restoration of processing is the reappearance of RT activity. These results suggest that for HIV-1 RT to be active, it must be matured from the pol polyprotein.
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PMID:Biosynthesis and analysis of a genetically engineered HIV-1 reverse transcriptase/endonuclease polyprotein in Escherichia coli. 246 29

Molecular evolution and phylogeny of different human immunodeficiency virus type 1 (HIV1) strains, of a type 2 (HIV2) strain, and of two simian immunodeficiency viruses (SIVAGM and SIVMAC) have been studied by comparing the nucleotide sequences of the two regions of their pol genes which encode the reverse transcriptase (RT) and endonuclease/integrase (EN). The analyses show that the different HIV 1s form one cluster (HIV1 group) and that the SIVs and HIV2 form another (HIV2 group). When the entire genomes of a HIV1, a HIV2, and the two SIVs were compared, the SIVAGM showed a unique pattern of mutation accumulations; that is, the SIVAGM has accumulated more nonsynonymous changes than synonymous changes in the RT and EN regions after its recent divergence from SIVMAC-142, and, furthermore, it has a deletion of approximately 350 bp in the region between the pol and env genes. The SIVAGM was apparently derived from cell cultures infected with a macaque isolate, SIVMAC-251. The contamination provides an opportunity to measure the maximum rate of evolution in the SIVAGM by comparing its DNA sequence to those of SIVMAC-251 and SIVMAC-142. The analysis shows that the rates are given approximately by (1.95 +/- 1.37) x 10(-3)/site/year for one SIVAGM sequence and (5.18 +/- 2.25) x 10(-3)/site/year for another.
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PMID:Molecular evolution of the human and simian immunodeficiency viruses. 246 34

A gene encoding the human immunodeficiency virus-1 (HIV-1) TAT protein was chemically synthesized and expressed in HeLa cells and in a cell-free system. To facilitate both the assembly of the synthetic gene and further mutagenesis and gene fusion studies, several unique restriction endonuclease cleavage sites were included in the coding sequence without altering the encoded protein sequence. The synthetic TAT coding sequence was fused to a translation start signal and placed under SV40 early transcriptional control. Co-transfection of the TAT-encoding synthetic gene together with a reporter gene (chloramphenical acetyl transferase or beta-galactosidase) linked to an HIV LTR confirmed that the synthetic gene product exhibits similar activity to TAT expressed from HIV genomic DNA in the transactivation of the LTR. TAT mRNA prepared by cell-free transcription of the synthetic TAT coding sequence was also shown to produce functional TAT following microinjection into HeLa-derived cells containing an integrated reporter gene with the HIV LTR linked to beta-galactosidase.
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PMID:Chemical synthesis and expression of a gene encoding HIV-1 TAT protein. 254

The rapid identification of anti-HIV compounds in the laboratory following the isolation of the causative virus in 1983 and their subsequent use in the clinic was not unexpected. Three decades of previous work had established a scientific basis for the evaluation of antiviral compounds. However, no antiviral yet discovered can cause total blockade of a virus replicating in a cell. The combination of properties of HIV including latency, antigenic and biochemical variation is unusual and the virus represents a daunting challenge for chemotherapy. But at least 90 antiviral compounds have been discovered, many inhibiting the virus reverse transcriptase. Other targets for inhibition are possible including viral regulatory gene products, viral protease and endonuclease enzymes but compounds for initial study will have to be found by random searching. X-ray crystallography of HIV proteins will shortly be possible, enabling the commencement of a more molecular specific search for inhibitors. Meanwhile, advantage can be taken of comparative nucleotide sequences of the HIV-1 and -2 genomes to test short oligonucleotides as potential inhibitors of mRNA transcription. The pol gene also has a zinc finger amino acid sequence suggesting that chelation chemotherapy may have a potential role. In the absence of HIV vaccines, and associated theoretical problems in their development, antiviral chemotherapy is expected to occupy a central role in combating the AIDS epidemic.
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PMID:Potential target sites for antiviral inhibitors of human immunodeficiency virus (HIV). 265 20

The umbilical cord blood from 109 consecutive Zambian neonates (excluding those found to be anti-HIV positive) were analysed for haemoglobin (Hb) Bart's and for alpha thalassaemia by restriction endonuclease analysis. This showed that 52.3% had the genotype alpha alpha/alpha alpha, 38.5% had -alpha 3.7/alpha alpha, 7.3% had -alpha 3.7/-alpha 3.7 and 1.8% had alpha alpha alpha/alpha alpha. The alpha thalassaemia gene (-alpha) frequency was 0.27. There were no apparent differences in gene frequency between six major Zambian ethnic groups. Detection of Hb Bart's identified all alpha-thalassaemia homozygotes (-alpha/-alpha), but fewer than 10% of heterozygotes (-alpha/alpha alpha). alpha-thalassaemia was associated with slight but significant anaemia and microcytosis.
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PMID:Alpha thalassaemia in Zambian newborn. 270 99

Human immunodeficiency virus-1 (HIV-1) isolates obtained from chimpanzees that had undergone various immunosuppressive treatments were characterized by growth on various primary cells and cell lines as well as by restriction endonuclease analysis. Viruses recovered from animals inoculated with uncloned HIV showed genetic variation from the original inoculum, whereas viruses isolated from an animal infected with a molecular clone of HIV did not. In some cases, virus recovery was possible only after enrichment for CD4+ cells by panning, inoculation with a chimpanzee cytomegalovirus, or a combination of these procedures. These findings indicate a role for viral and host cofactors in the control of virus replication and suggest explanations for the absence of clinical manifestations in HIV-infected chimpanzees.
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PMID:Human immunodeficiency virus (HIV) from experimentally infected chimpanzees: isolation and characterization. 276 Sep 17

Serum samples from 247 patients with positive HIV-1 IgG serology were investigated for specific IgM antibodies. We found that 109 also reacted positively with a least one antigen in an HIV-1 IgM Western Blot and only 31 in an HIV-1 IgM enzyme-linked immunosorbent assay (ELISA). It was shown that in some of the persons, specific IgM antibodies against the gp160/120, p66, p55, gp41, p24, and p17 antigens of the virus are synthesized at some time after infection. IgM antibodies to the endonuclease-related p31 antigen were observed in one serum only. IgM antibodies against the gp160/120, p66, gp41, and p17 antigens seemed to disappear early after infection. Those against the p55 and the p24 antigens were found in 62% and 75% of investigated cases, respectively. A direct correlation between the Western Blot patterns and the IgM ELISA results was not found.
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PMID:Detection of anti-HIV-1 immunoglobulin M antibodies in patients with serologically proved HIV-1 infection. 316 78

A cytopathic human immunodeficiency virus type 1 (HIV-1) isolate containing multiple virus genotypes was molecularly cloned, and the biological activity of six randomly selected clones was assessed by transfection into human lymphoid or glial cell lines. Five infectious clones of HIV-1, termed N1T-A through -E, were isolated in this manner. Clones N1T-A, -B, -C, and -E could be distinguished by restriction endonuclease mapping whereas clones N1T-B and -D had identical maps with the enzymes used. Each clone exhibited a distinct host cell range as well as markedly different infection kinetics and cytopathogenic properties when tested in human cell lines of T-lymphocytic, monocytic, and astrocytic origin. In particular, infection with HIV-1 clone N1T-E was characterized by slow kinetics and lack of significant cytopathic effects in acutely and chronically infected cells. Clone N1T-A, similar to the parental isolate N1T, exhibited a wide host cell range, fast kinetics of infection, and high cytopathogenicity. These data indicate that HIV-infected individuals may carry multiple HIV-1 genotypes with distinct cytopathogenic potential and cell tropism. Analysis of virus isolates must take into account the contribution, or masking, of individual virus clones.
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PMID:Differences in cytopathogenicity and host cell range among infectious molecular clones of human immunodeficiency virus type 1 simultaneously isolated from an individual. 317 38


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