Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019693 (HIV)
 170,526 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Epstein-Barr virus (EBV) infection is associated with Burkitt's lymphoma (BL) in normal individuals and immunoblastic B cell lymphomas in immunosuppressed or HIV-infected individuals. SCID mice reconstituted with human peripheral blood leukocytes (hu-PBL-SCID) from EBV-seropositive donors also may develop spontaneous B cell lymphomas which histologically and phenotypically resemble post-transplant tumors, and are distinct from BL. These tumors always contain EBV DNA. We have noted three different reproducible outcomes depending upon the EBV-seropositive donor used for generation of hu-PBL-SCID mice: (i) no tumors appear; (ii) tumors appear in a fraction of hu-PBL-SCID mice with a 10-20 wk. latent period; or (iii) tumors appear in all hu-PBL-SCID mice within 6-10 wk. Southern blot analysis of late versus early tumors using a probe specific for the EBV terminal repeat sequences (BamNJ), which allows distinction between circular latent and linear replicating genomes, shows that late tumors do not involve active EBV replication but that early tumors do show replicating genomes. In addition, EBV genomes were monoclonal in late tumors but polyclonal in early tumors. These data suggest two mechanisms for EBV lymphomagenesis, slow outgrowth of rare latently-infected B cells, and more rapid transformation of uninfected bystander B cells by replicating virus. The latter process may be highly amenable to therapy in patients at risk for EBV-related lymphomas. In addition, prospective screening of EBV-seropositive transplant recipients in the hu-PBL-SCID model may predict the risk of post-transplant lymphoma development.
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PMID:EBV-induced human B cell lymphomas in hu-PBL-SCID mice. 132 70

T cells in the peripheral blood are largely in the resting state and represent a significant pool of potential targets for HIV infection. The protection of these cells from infection is an important goal of nucleoside therapy. Resting PBL may not be protected effectively by such nucleosides as azidothymidine (AZT) since anabolic phosphorylation of thymidine nucleosides is reported to be limited in these cells. In this study we used DNA amplification procedures to follow HIV proviral DNA formation in resting T cells and to determine the ability of azidodeoxythymidine (AZT), dideoxyinosine (ddI), and dideoxycytosine (ddC) to inhibit this process. Experiments confirm that resting PBL synthesize HIV proviral DNA sequences. Drug titrations showed that this synthesis could be inhibited by nucleosides. ddC was the most potent drug, inhibiting transcription at the U5 region. ddI and AZT at similar concentrations (10 microM) did not inhibit. ddI in the concentration range of 10-100 microM was able to inhibit production of transcripts containing U3 and env sequences in resting cells. Similar inhibition levels were accomplished by AZT at 10-100-fold lower drug concentrations. These results demonstrate that resting T cells can be protected from HIV infection by nucleosides and that thymidine nucleosides are effective inhibitors despite the limited potential for anabolic phosphorylation.
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PMID:Inhibition of HIV infection of resting peripheral blood lymphocytes by nucleosides. 132 18

In the current study, 35 pairs of corneas from asymptomatic carriers of HIV-1 and ten pairs from AIDS patients were analyzed for the presence of HIV-1 and HHV-6. The tissues were evaluated for viral antigens, transcripts, DNA sequences and intact and infectious virus. Three corneas from two asymptomatic carriers of HIV-1 and three corneas from two AIDS patients were culture positive for HIV-1. One of the three HIV-1 positive corneas from an asymptomatic HIV-1 carrier also was culture positive for HHV-6. Two of the tissue culture positive corneas from asymptomatic HIV-1 carriers and two from AIDS patients also tested positive for HIV-1 transcriptional activity by in situ hybridization. The label denoting the transcriptional activity was limited to stromal keratocytes. Most significantly, we were able to demonstrate the presence of HIV-1 particle(s) in sections and cultured PBMC from one of the HIV-1 culture positive corneas. PBMC from the same cornea also contained herpes virus particles. This report strengthens our earlier findings that HIV-1 and HHV-6 can invade corneal tissue, which emphasizes the importance of vigorous screening of corneal donors, specifically donors with HIV-1 exposure.
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PMID:Frequency of dual infections of corneas with HIV-1 and HHV-6. 132 27

This study determined the frequency of multiple viral (HIV-1, HHV-6, and CMV) infections in 26 retinas from 16 AIDS patients. Of the 12 retinas of 26 that tested positive for HIV-1 DNA sequences, seven also were positive for HHV-6 DNA sequences. Four of these seven retinas were culture positive for HIV-1 and two of the four contained CMV DNA sequences and antigens. Using RNA probes, HIV-1 and HHV-6 transcriptional activity was demonstrated in two of the four HIV-1 culture positive retinas. These retinas also contained CMV DNA sequences and antigens. The results demonstrate that more than 35% of AIDS patients suffer from at least two simultaneous viral infections and 15% suffer from three viral infections. The presence of transcriptional activity of HIV-1 and HHV-6 suggests an active infection.
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PMID:Transcriptional activity of HIV-1 and HHV-6 in retinal lesions from AIDS patients. 132 93

Recently, the capability for determining the high-resolution, sequence-dependent structure of oligonucleotides in solution via careful analysis of multidimensional NMR spectra and structure refinement procedures has been developed. Consequently, the rationale for selection of a genome sequence as a target for drug design based on the detailed three-dimensional structure of the target is presented. The concept is illustrated by the successful search for a highly conserved region of the HIV-1 genome's long terminal repeat which could serve as a molecular target. A compound which could selectively bind the target sequence could inhibit both RNA transcription from the integrated provirus and the reverse transcription process. Of 148 unique HIV-1 sequences examined, 147 exhibit a 21-base conserved sequence (nucleotides 70-90 in HIVHXB2R) in the R region of the long terminal repeat. The only exception, a minor constituent for one individual, has a change in the penultimate base. A 13 base pair duplex sequence, [d(AGCTTGCCTTGAG).d(CTCAAGGCAAGCT)], from this conserved region was selected and synthesized for NMR structure studies. Phase-sensitive proton two-dimensional nuclear Overhauser enhancement (2D NOE) and double-quantum-filtered correlation (2QF-COSY) spectra were obtained at 500 MHz for the DNA duplex. Exchangeable and nonexchangeable proton resonances were assigned. Quantitative assessments of the 2D NOE cross-peak intensities for different mixing times were carried out using conventional Fourier transform NMR and the maximum likelihood method (MLM). Distance constraints, along with upper and lower bounds, were obtained from the 2D NOE intensities using the iterative complete relaxation matrix algorithm MARDIGRAS. Distances entailing both exchangeable and nonexchangeable protons were determined: 7-11 experimental distance constraints per residue including interresidue and interstrand distances. Simulations of the scalar coupling effects manifest in 2QF-COSY cross-peaks by means of the program SPHINX/LINSHA were compared with experimental data to yield torsion angle constraints for the sugar rings. A single conformer was inadequate to describe any of the sugar puckers, but a rapid two-state equilibrium with one conformer strongly dominant (75-95%) provided a good fit of the 2QF-COSY cross-peaks. The sugar pucker of the major conformer exhibited significant variability for the various nucleotides but was roughly 2'-endo. Though derived independently and subject to different time-averaging effects, the 2QF-COSY and 2D NOE results are in accord.
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PMID:A potential gene target in HIV-1: rationale, selection of a conserved sequence, and determination of NMR distance and torsion angle constraints. 132 12

To investigate the association between human immunodeficiency virus (HIV) and Epstein-Barr virus (EBV), simultaneous determinations of HIV antigen (HIV Ag) p24 and EBV DNA were performed in lymphocyte culture supernatants from 63 individuals at risk of HIV infection. In vitro data, together with HIV immune status results, were subjected to a statistical analysis. HIV infection was identified in 49 patients (78%); of these, in vitro EBV DNA was found in 44 individuals (90%), while in only 3 of the 14 non-infected ones (21%). Statistical analysis demonstrated a close relationship between evidence of HIV infection and in vitro detection of EBV DNA (87.3% concordant with 95% confidence interval: 76.5%-94.5%). Furthermore, a strong dependence was revealed between the presence of EBV DNA and HIV Ag in culture (p less than 0.00001). These results indicate the existence of in vitro viral interactions, with likely in vivo implications in the pathogenesis and evolution of HIV infection.
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PMID:Evidence of an in vitro association between human immunodeficiency virus antigen P24 and Epstein-Barr virus DNA. 132 86

Cutaneous papillomavirus infection is common in patients who are immunosuppressed. We describe swollen keratinocytes in the granular layer in lesions from four patients who had human immunodeficiency virus infection. These cells were similar to those described in skin lesions of epidermodysplasia verruciformis. Amplification of DNA from the lesions revealed an amplimer for human papillomavirus using a consensus primer for a highly conserved region of the L1 open reading frame; however, specific binding was not noted when radiolabelled probes for human papillomavirus types 6, 11, 16, 18, and 33 were used. We conclude that the presence of these distinctive swollen cells strongly suggests immunosuppression and quite possibly infection by a less common papillomavirus type.
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PMID:Swollen keratinocytes: a histologic marker of unusual human papillomavirus-type infection and immunosuppression. 132 33

In HIV-infected men, human papillomavirus (HPV) infection is strongly linked with the development of anogenital lesions but is not a sufficient factor to explain the neoplastic transformation of such lesions. We investigated the association between HPV and herpesvirus infections in penile and anal lesions from 54 HIV-seronegative and 54 HIV-seropositive men by means of colposcopy, histopathology and in situ hybridization. Our patients showed condyloma acuminata (39%), papular warts (35%) and macular warts (26%). High-grade lesions were predominant in the HIV+ men, whereas low-grade lesions were more frequent in the HIV- men. In the HIV+ group, potential oncogenic HPV were the most frequently detected (83.4%) whereas the "low-risk" HPV were found chiefly in HIV- men (62.1%). The CD4 number was lower in patients showing "high-risk" HPV than in men showing lesions without HPV or with non-oncogenic HPV. HPV types 6/11 were found mainly associated with koilocytosis or with AIN(PIN)I. Oncogenic HPV were more often detected in AIN(PIN)II-III. The herpesviruses DNA detection revealed a higher prevalence of HSVI and -2 than CMV and EBV in the studied biopsies. The frequency of HSV and CMV detection was higher in the HIV+ than in the HIV- men. A link was found between the "high-risk" HPV and the CMV detection whatever the population considered. The detection in HPV lesions of other sexually transmitted viral agents could therefore represent an important means of preventing progression of the anogenital disease, especially in immunosuppressed patients.
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PMID:Viral co-infections in human papillomavirus-associated anogenital lesions according to the serostatus for the human immunodeficiency virus. 133 Sep 31

Human papillomavirus (HPV) DNA was found in cervicovaginal lavage fluids from 9 of 11 human immunodeficiency virus type 1 (HIV-1)-seropositive female prostitutes with cervical intraepithelial neoplasia (CIN) in Kinshasa, Zaire. Since 7 yielded complex nucleic acid hybridization results consistent with mixed HPV infections, limited sequencing of HPV DNA was used to identify the HPVs present. Three of HPV 16 and 1 each of HPV 18, 31, 33, and 56 and ME180-HPV were identified by sequencing in 8 samples. Each of these genotypes has been found in specimens from HIV-1-seronegative women with CIN. Some DNAs had nucleic acid and amino acid sequence variations relative to the reference HPVs, but the variants were closely related to variants that have been found in HIV-1-seronegative women. Variant amino acids were found predominantly at three positions in one 40-amino-acid segment of the L1 open reading frame sequenced. The predominant HPV 16 variant observed has been found rarely in other countries.
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PMID:Genotypes and sequence variants of human papillomavirus DNAs from human immunodeficiency virus type 1-infected women with cervical intraepithelial neoplasia. 133 Dec 47

Microinjection of wild-type adeno-associated virus type 2 (AAV-2) DNA and infectious human immunodeficiency virus type 1 (HIV-1) proviral DNA into the nuclei of human epithelioid SW480 cells leads to specific inhibition of HIV-1 replication. Mutational analysis of the AAV genome showed that this negative interference can be assigned to a functional AAV-2 rep gene. Moreover, the p78rep/p68rep proteins are sufficient for the anti-HIV-1 effects. The rep gene also inhibits the expression of a chloramphenicol acetyl-transferase (CAT) gene driven by the U3/R portion of the HIV-1 long terminal repeat (LTR) in the absence of tat expression. This suggests that the U3/R portion of HIV-1 contains elements responsible for the AAV-2 rep-mediated inhibition of HIV-1 LTR-driven CAT gene expression and, probably, also of HIV-1 replication. The results add support for the general significance of AAV-2 and specifically the rep gene as tools for down-regulating heterologous gene expression.
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PMID:Adeno-associated virus type 2-mediated inhibition of human immunodeficiency virus type 1 (HIV-1) replication: involvement of p78rep/p68rep and the HIV-1 long terminal repeat. 133 Dec 99


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