Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0021051 (immunodeficiency)
 71,517 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have used the technique of in vitro selection to generate variants of human immunodeficiency virus type 1 (HIV-1) that are resistant to 2',3'-dideoxyinosine (ddI) and cross-resistant to 2',3'-dideoxycytidine (ddC). The complete reverse transcriptase (RT)-coding regions, plus portions of flanking sequences, of viruses possessing a ddI-resistant phenotype were cloned and sequenced by polymerase chain reaction (PCR)-based methods. We observed that several of these viruses possessed mutations at amino acid sites 184 (Met-->Val; ATG-->GTG) and 294 (Pro-->Ser; CCA-->TCA). These mutations were introduced in the pol gene of infectious, cloned HXB2-D DNA by site-directed mutagenesis. Viral replication assays confirmed the importance of site 184 with regard to resistance to ddI. The recombinant viruses thus generated displayed more than fivefold-greater resistance to ddI than parental HXB2-D did. Moreover, more than fivefold-greater resistance to ddC was also documented; however, the recombinant viruses continued to be inhibited by zidovudine (AZT). No resistance to ddI, ddC, or AZT was introduced by inclusion of mutation site 294 in the pol gene of HXB2-D. PCR analysis performed on viral samples obtained from patients receiving long-term ddI therapy confirmed the presence of mutation site 184 in five of seven cases tested. In three of these five positive cases, the wild-type codon was also detected, indicating that mixtures of viral quasispecies were apparently present. Viruses possessing a ddI resistance phenotype were isolated from both subjects whose viruses contained only the mutated rather than wild-type codon at position 184 as well as from a third individual, whose viruses appeared to be mostly of the mutated variety.
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PMID:Novel mutation in the human immunodeficiency virus type 1 reverse transcriptase gene that encodes cross-resistance to 2',3'-dideoxyinosine and 2',3'-dideoxycytidine. 127 98

Increased levels of inflammatory cytokines, including tumor necrosis factor (TNF), interleukin-1 (IL-1), and IL-6, have been detected in specimens from human immunodeficiency virus type 1 (HIV-1)-infected individuals. Here we demonstrate that HIV-1 activates the expression of TNF but not of IL-1 and IL-6 in acutely and chronically infected T cells. The increase in TNF gene expression is due to activation of the TNF promoter by the viral gene product Tat. Transactivation of TNF gene expression requires the product of the first exon of the tat gene and is cell type independent. T cells chronically infected with pol-defective HIV-1 provirus constitutively express both Tat and TNF at levels significantly higher (fivefold) than those seen in control cells, and treatment with phorbol myristate acetate greatly enhances Tat expression and TNF production. As TNF can increase the production of IL-1 and IL-6 and these inflammatory cytokines all enhance HIV-1 gene expression and affect the immune, vascular, and central nervous systems, the activation of TNF by Tat may be part of a complex pathway in which HIV-1 uses viral products and host factors to increase its own expression and infectivity and to induce disease.
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PMID:Effects of the human immunodeficiency virus type 1 Tat protein on the expression of inflammatory cytokines. 127 99

The pol genes of retroviruses are translated as gag-pol fusion proteins by ribosomal frameshifting within the gag-pol overlap region. During the ribosomal frameshift event, the gag open reading frame is shifted -1 nt to allow in-phase reading of the pol open reading frame. A consensus frameshift signal sequence of GGGAAAC within the gag-pol overlap region of feline immunodeficiency virus (FIV) has been identified followed by a sequence that has the potential for a pseudoknot tertiary structure. Using recombinant baculoviruses in which the frameshift occurs efficiently, the consensus sequence has been shown to be the site of the frameshift event. A mutation creating a termination codon just downstream of the putative frameshift signal sequence but upstream of the potential pseudoknot structure made a shorter gag product, but did not affect the efficiency of frameshifting. A mutation creating a termination codon just upstream of the putative frameshift signal made a shorter product and essentially abrogated frameshifting. Mutations in the first stem or the second stem in the potential pseudoknot structure severely reduced the frameshifting efficiency. Mutations which altered the length between the frameshift signal and the pseudoknot structure (the so-called spacer region) also reduced the frameshift efficiency. The insertion of a palindromic sequence, which could form a hairpin structure just upstream of the frameshift signal sequence, also affected the frameshifting. These results support the view that the ribosomal frameshift event in the FIV gag-pol region involves the identified signal sequence and appears to require the precisely positioned downstream sequence and indicated pseudoknot structure for efficient frameshifting.
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PMID:Identification and analysis of the gag-pol ribosomal frameshift site of feline immunodeficiency virus. 131 Jan 75

To develop the polymerase chain reaction (PCR) for the detection of simian T-lymphotropic virus type I (STLV-I) infection, cell lines or peripheral-blood mononuclear cells (PBMC) from 2 non-human primate species [African green monkeys (AGM), Cercopithecus aethiops; baboon, Papio cynocephalus] were evaluated for their STLV-I status using oligonucleotide primer pairs and probes specific for the tax and pol gene regions of the closely related human T-lymphotropic virus type I (HTLV-I). These PCR results were compared with serologic (Western blot assay) and viral culture (p24-antigen capture assay) data. PCR products for both gene regions were detected in established baboon, Japanese macaque and rhesus macaque STLV-I-producing cell lines. STLV-I tax and pol products were also detected in PBMC from 4 of 4 infected AGM and 4 of 4 infected baboons, each of which were also Western-blot-positive and p24-antigen-capture-positive. Of the remaining AGM (n = 7) and baboon (n = 1) which were PCR-negative, each was also Western-blot-negative and p24-antigen-capture-negative. Two seronegative and virus-culture-negative AGM were classified as PCR indeterminate with weak reactivity using tax primers. These primer pairs failed to amplify DNA from uninfected human PBMC, an uninfected human lymphoid cell line, a simian immunodeficiency virus macaque (SIVmac251)-infected cell line and a simian-retrovirus-type-D(SRV-D)-infected cell line. HTLV-II-pol-specific primer pairs failed to amplify DNA from STLV-I-infected cell lines and PBMC from STLV-I-infected monkeys. Further, HTLV-I pol and tax primer pairs successfully amplified RNA from HTLV-I- and STLV-I-infected cell lines by reverse transcriptase (RT)-PCR. We have demonstrated excellent specificity in the detection of STLV-I by PCR using these HTLV-I-derived primers and probes. Additionally, our data suggest that the tax and pol gene regions are conserved between HTLV-I and STLV-I strains found among these diverse species of non-human primates.
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PMID:Detection of simian T-lymphotropic virus type I using the polymerase chain reaction. 131 66

The nonstructural/regulatory genes of human immunodeficiency virus type 1 (HIV-1) and other lentiviruses are believed to play an important role in the replication and pathogenesis of these viruses. In HIV-1 and other lentiviruses, the vif (viral infectivity factor) open reading frame (ORF) (also termed sor or Q in some lentivirus genomes) is located in the central region, overlapping the 3' end of the pol ORF, but in a different reading frame. Among the lentiviruses, only equine infectious anemia virus lacks a vif ORF. The predicted Vif protein sequences from 38 lentiviruses were analyzed for the presence of global and local sequence similarity. The Vif proteins of closely related lentiviruses are highly conserved (HIV-1HXB2:HIV-1mn = 91% identity), while those of more distantly related lentirviruses have diverged significantly (HIV-1HXB2:simian immunodeficiency virusmax = 30% identity). A search for local sequence similarity revealed that a unifying feature of predicted lentivirus Vif proteins is the presence of at least one of two short, highly conserved sequence motifs, SL(I/V)X4YX9Y and SLQXLA. SLQXLA was present in 34 of 38 lentiviruses examined, while the remaining four lentiviruses had one (three viruses) or two (one virus) substitutions in this motif (of five total substitutions, three were conservative changes). The SL(I/V)X4YX9Y motif was found only in primate lentiviruses and in bovine immunodeficiency-like virus. Based on these findings, we suggest that the locus designation vif be used to denote all lentivirus ORFs previously called vif, Q, or sor.
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PMID:Conservation of amino-acid sequence motifs in lentivirus Vif proteins. 131 56

We have molecularly cloned the complete genomic DNA of TM2 strain of feline immunodeficiency virus (FIV) isolated in Japan and compared its nucleotide and the deduced amino acid sequence with those of previously described U.S. isolates, FIV Petaluma and FIV PPR. The infectious molecular clone of FIV TM2 is different from FIV Petaluma in host cell range; the clone can not infect Crandell feline kidney cells which were permissive for FIV Petaluma. The amino acid sequence homologies, in gag, pol, and env genes between FIV TM2 and Petaluma were 90%, 87%, and 81%, respectively. On the other hand, comparative analysis of each gene between FIV Petaluma and PPR showed 96,95, and 85%, respectively. These results suggested that the genomic diversity was present among FIV strains isolated from geographically distant areas. Interestingly, tat- and rev-like short open reading frames contained inframe stop codons in the FIV Petaluma but not in the FIV TM2.
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PMID:Molecular characterization and heterogeneity of feline immunodeficiency virus isolates. 131 25

A specific and sensitive polymerase chain reaction (PCR) procedure for the detection of feline immunodeficiency virus (FIV) in peripheral blood mononuclear cells (PBMC) was developed. PBMC from both blood samples and cultures were digested by proteinase K in a lysis buffer, and after heat inactivation of the proteinase, the resultant material was used in a two step amplification protocol using nested sets of primers. Two independent amplifications, from the gag and pol genes respectively, were performed in each tube. The PCR was positive for six of 14 samples from FIV seropositive adult cats, while all 36 samples from seronegative cats were negative. In comparison with an antigen-capturing ELISA procedure, the PCR detected FIV infection in PBMC cultures on average two days earlier.
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PMID:Detection of feline immunodeficiency virus by a nested polymerase chain reaction. 131 23

To investigate whether human immunodeficiency virus type 1 pol gene mutations are selected during prolonged 2',3'-dideoxycytidine (ddC) therapy, we used the polymerase chain reaction to amplify a portion of the reverse transcriptase segment of the pol gene from the peripheral blood mononuclear cell DNA of a patient with AIDS before and after an 80-week course of ddC therapy. The consensus sequence from the second sample contained a unique double mutation (ACT to GAT) in the codon for reverse transcriptase amino acid 69, causing substitution of aspartic acid (Asp) for the wild-type threonine (Thr). A mutation (ACA to ATA) also occurred in the codon for position 165, causing substitution of isoleucine (Ile) for Thr. The GAT (Asp) codon was introduced into the pol gene of a molecular clone of human immunodeficiency virus via site-directed mutagenesis. Following transfection, mutant and wild-type viruses were tested for susceptibility to ddC by a plaque reduction assay. The mutant virus was fivefold less susceptible to ddC than the wild type; cross-resistance to 3'-azido-3'-deoxythymidine or 2'3'-dideoxyinosine was not found. The Ile-165 mutation did not confer additional ddC resistance. The Asp-69 substitution may have contributed to the generation of resistant virus in this patient.
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PMID:Human immunodeficiency virus type 1 pol gene mutations which cause decreased susceptibility to 2',3'-dideoxycytidine. 131 43

The human immunodeficiency virus type 1 (HIV-1) Gag-Pol fusion polyprotein is produced via ribosomal frameshifting. Previous studies in vitro and in Saccharomyces cerevisiae have argued against a significant role for RNA secondary structure 3' of the shift site, in contrast with other systems, in which such structure has been shown to be required. Here we show, by expressing the HIV-1 gag-pol domain in cultured vertebrate cells, that a stem-loop structure 3' of the HIV-1 shift site is indeed important for wild-type levels of frameshifting in vivo.
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PMID:Human immunodeficiency virus type 1 gag-pol frameshifting is dependent on downstream mRNA secondary structure: demonstration by expression in vivo. 132 Dec 94

The Food and Drug Administration (FDA) has recommended that all donated blood be screened for antibodies to human immunodeficiency virus type 2 (HIV-2) beginning no later than June 1, 1992. This article provides CDC recommendations for the diagnosis of HIV-1 and HIV-2 infections in persons being tested in settings other than blood centers and CDC/FDA guidelines for serologic testing with combination HIV-1/HIV-2 screening enzyme immunoassays (EIAs). Epidemiologic data indicate that the prevalence of HIV-2 infections in persons in the United States is extremely low. Therefore, CDC does not recommend routine testing for HIV-2 in settings other than blood centers. However, when HIV testing is indicated, tests for antibodies to both HIV-1 and HIV-2 should be obtained if epidemiologic risk factors for HIV-2 infection are present, if clinical evidence exists for HIV disease in the absence of a positive test for antibodies to HIV-1, or if HIV-1 Western blot results exhibit the unusual indeterminate pattern of gag plus pol bands in the absence of env bands. The following procedures are recommended if testing for both HIV-1 and HIV-2 is performed by means of a combination HIV-1/HIV-2 EIA. A repeatedly reactive specimen by HIV-1/HIV-2 EIA should be tested by HIV-1 Western blot (or another licensed HIV-1 supplemental test). A positive result by HIV-1 Western blot confirms the presence of antibodies to HIV, and testing for HIV-2 is recommended only if HIV-2 risk factors are present. If the HIV-1 Western blot result is negative or indeterminate, an HIV-2 EIA should be performed. If the HIV-2 EIA is positive, an HIV-2 supplemental test should be performed.
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PMID:Testing for antibodies to human immunodeficiency virus type 2 in the United States. 132 95


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