scholarly journals Biochemical and Genetic Definition of the Cellular Protease Required for HIV-1 gp160 Processing

1995 ◽  
Vol 270 (7) ◽  
pp. 3154-3159 ◽  
Author(s):  
Alex Franzusoff ◽  
Alison M. Volpe ◽  
Denise Josse ◽  
Sergio Pichuantes ◽  
Joseph R. Wolf
Keyword(s):  
Definition Of ◽  
Hiv 1 ◽  
Cellular Protease

scholarly journals Lattice engineering enables definition of molecular features allowing for potent small-molecule inhibition of HIV-1 entry

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Yen-Ting Lai ◽  
Tao Wang ◽  
Sijy O’Dell ◽  
Mark K. Louder ◽  
Arne Schön ◽  
...  
Keyword(s):  
Small Molecule ◽  
Molecular Features ◽  
Small Molecule Inhibition ◽  
Definition Of ◽  
Hiv 1

Clinical Features and Serum β2-Microglobulin Levels in HIV-1 Positive and Negative Tanzanian Patients with Tuberculosis

1995 ◽  
Vol 6 (4) ◽  
pp. 278-283 ◽  
Author(s):  
Nick Kennedy ◽  
Fiona M Whitelaw ◽  
Jacques Gutmann ◽  
Leslie Berger ◽  
Leonard Uiso ◽  
...  
Keyword(s):  
Pulmonary Tuberculosis ◽  
Clinical Features ◽  
Active Tuberculosis ◽  
Hiv Positive ◽  
Hiv Disease ◽  
Β2 Microglobulin ◽  
Median Serum ◽  
Definition Of ◽  
Hiv 1 ◽  
Hiv Negative

Summary: Serum β2-microglobulin (β2M) rises in the later stages of HIV disease and has therefore been used to monitor progression to AIDS. However, little work has been done on patients co-infected with HIV and tuberculosis. We studied clinical features and serum β2-M in 35 Tanzanian patients treated for pulmonary tuberculosis (9 HIV-positive, 26 HIV-negative). The provisional WHO clinical definition of AIDS for use in Africa was fulfilled by 89% of the HIV-positive and 65% of the HIV-negative patients. Median serum β2-M on admission was slightly higher in HIV-positive (3.17 mg/l) than in HIV-negative (2.85 mg/1) patients. Serum β2-M fell during treatment in 17/24 (71%) of HIV-negative and 3/7 (43%) HIV-positive patients followed up for 6 months. We conclude that serum β2-M is frequently raised in active tuberculosis, and is therefore an unreliable indicator of the stage of HIV disease in co-infected patients. The WHO clinical definition of AIDS also proved unreliable in patients with tuberculosis.

scholarly journals Excessive RNA Splicing and Inhibition of HIV-1 Replication Induced by Modified U1 Small Nuclear RNAs

2010 ◽  
Vol 84 (24) ◽  
pp. 12790-12800 ◽  
Author(s):  
Dibyakanti Mandal ◽  
Zehua Feng ◽  
C. Martin Stoltzfus
Keyword(s):  
Rna Splicing ◽  
Virus Production ◽  
Viral Rna ◽  
Splice Sites ◽  
Rna Transcripts ◽  
Cellular Factors ◽  
Novel Strategy ◽  
Definition Of ◽  
T Cell Lines ◽  
Hiv 1

ABSTRACT HIV-1 RNA undergoes a complex splicing process whereby over 40 different mRNA species are produced by alternative splicing. In addition, approximately half of the RNA transcripts remain unspliced and either are used to encode Gag and Gag-Pol proteins or are packaged into virions as genomic RNA. It has previously been shown that HIV-1 splicing is regulated by cis elements that bind to cellular factors. These factors either enhance or repress definition of exons that are flanked by the HIV-1 3′ splice sites. Here we report that expression of modified U1 snRNPs with increased affinity to HIV-1 downstream 5′ splice sites and to sequences within the first tat coding exon act to selectively increase splicing at the upstream 3′ splice sites in cotransfected 293T cells. This results in a decrease of unspliced viral RNA levels and an approximately 10-fold decrease in virus production. In addition, excessive splicing of viral RNA is concomitant with a striking reduction in the relative amounts of Gag processing intermediates and products. We also show that T cell lines expressing modified U1 snRNAs exhibit reduced HIV-1 replication. Our results suggest that induction of excessive HIV-1 RNA splicing may be a novel strategy to inhibit virus replication in human patients.

Case Definitions for Paediatric AIDS: The Zambian Experience

1993 ◽  
Vol 4 (2) ◽  
pp. 83-85 ◽  
Author(s):  
C Chintu ◽  
A Malek ◽  
M Nyumbu ◽  
C Luo ◽  
J Masona ◽  
...  
Keyword(s):  
Positive Predictive Value ◽  
Predictive Value ◽  
Clinical Case ◽  
Case Definition ◽  
World Health ◽  
Who Criteria ◽  
Number Of Patients ◽  
Definition Of ◽  
Hiv 1 ◽  
Clinical Case Definition

For the purpose of surveillance of the acquired immunodeficiency syndrome (AIDS) in developing countries, the World Health Organization (WHO) has recommended criteria for the clinical case definition of AIDS in adults and children. In a preliminary examination of children in Zambia a number of patients with obvious AIDS did not fit the published WHO case definition for paediatric AIDS. Based on this the Zambia National AIDS Surveillance Committee designed local criteria for the clinical case definition of paediatric AIDS. We compared the Zambian criteria with the WHO criteria for the diagnosis of paediatric AIDS by studying 134 consecutively admitted children to one of the paediatric wards at the University Teaching Hospital in Lusaka. Twenty-nine of the patients were HIV-1 seropositive and 105 were HIV-1 seronegative. Among the 29 HIV-seropositive patients, the Zambian criteria identified 23, and the WHO criteria identified 20 children as having AIDS. The 105 HIV-seronegative children were classified as having AIDS in 9 cases by the Zambian criteria and in 38 cases by the WHO criteria. These results give the Zambian criteria for the diagnosis of AIDS a sensitivity of 79.3%, a specificity of 91.4% and a positive predictive value of 86.8% compared to a sensitivity of 69%, specificity of 64% and a positive predictive value of 38% for the WHO criteria. The current WHO criteria are inadequate for the diagnosis of paediatric AIDS. The need to refine the WHO criteria for the diagnosis of paediatric AIDS is discussed.

scholarly journals Definition of the viral targets of protective HIV-1-specific T cell responses

2011 ◽  
Vol 9 (1) ◽  
pp. 208 ◽  
Author(s):  
Beatriz Mothe ◽  
Anuska Llano ◽  
Javier Ibarrondo ◽  
Marcus Daniels ◽  
Cristina Miranda ◽  
...  
Keyword(s):  
T Cell ◽  
T Cell Responses ◽  
Cell Responses ◽  
Definition Of ◽  
Hiv 1

scholarly journals Identification of a New HIV-1 BC Intersubtype Circulating Recombinant Form (CRF108_BC) in Spain

Viruses ◽  
2021 ◽  
Vol 13 (1) ◽  
pp. 93
Author(s):  
Javier E. Cañada ◽  
Elena Delgado ◽  
Horacio Gil ◽  
Mónica Sánchez ◽  
Sonia Benito ◽  
...  
Keyword(s):  
Phylogenetic Analyses ◽  
Basque Country ◽  
Recent Common Ancestor ◽  
Subtype C ◽  
Northern Spain ◽  
Most Recent Common Ancestor ◽  
Phylogenetic Cluster ◽  
Subtype B ◽  
Definition Of ◽  
Hiv 1

The extraordinary genetic variability of human immunodeficiency virus type 1 (HIV-1) group M has led to the identification of 10 subtypes, 102 circulating recombinant forms (CRFs) and numerous unique recombinant forms. Among CRFs, 11 derived from subtypes B and C have been identified in China, Brazil, and Italy. Here we identify a new HIV-1 CRF_BC in Northern Spain. Originally, a phylogenetic cluster of 15 viruses of subtype C in protease-reverse transcriptase was identified in an HIV-1 molecular surveillance study in Spain, most of them from individuals from the Basque Country and heterosexually transmitted. Analyses of near full-length genome sequences from six viruses from three cities revealed that they were BC recombinant with coincident mosaic structures different from known CRFs. This allowed the definition of a new HIV-1 CRF designated CRF108_BC, whose genome is predominantly of subtype C, with four short subtype B fragments. Phylogenetic analyses with database sequences supported a Brazilian ancestry of the parental subtype C strain. Coalescent Bayesian analyses estimated the most recent common ancestor of CRF108_BC in the city of Vitoria, Basque Country, around 2000. CRF108_BC is the first CRF_BC identified in Spain and the second in Europe, after CRF60_BC, both phylogenetically related to Brazilian subtype C strains.

Definition of an 18-mer Synthetic Peptide Derived from the GB virus C E1 Protein as a New HIV-1 Entry Inhibitor

2016 ◽  
Vol 1860 (6) ◽  
pp. 1139-1148 ◽  
Author(s):  
M.J. Gómara ◽  
V. Sánchez-Merino ◽  
A. Paús ◽  
A. Merino-Mansilla ◽  
J.M. Gatell ◽  
...  
Keyword(s):  
Synthetic Peptide ◽  
Entry Inhibitor ◽  
Gb Virus C ◽  
E1 Protein ◽  
Definition Of ◽  
Virus C ◽  
Hiv 1

scholarly journals Structure-Activity Analysis of Vinylogous Urea Inhibitors of Human Immunodeficiency Virus-Encoded Ribonuclease H

2010 ◽  
Vol 54 (9) ◽  
pp. 3913-3921 ◽  
Author(s):  
Suhman Chung ◽  
Michaela Wendeler ◽  
Jason W. Rausch ◽  
Greg Beilhartz ◽  
Matthias Gotte ◽  
...  
Keyword(s):  
Reverse Transcriptase ◽  
Single Molecule ◽  
Thiophene Ring ◽  
Rnase H ◽  
Single Molecule Spectroscopy ◽  
Inhibitor Binding ◽  
Structure Activity ◽  
Immunodeficiency Virus ◽  
Definition Of ◽  
Hiv 1

ABSTRACT Vinylogous ureas 2-amino-5,6,7,8-tetrahydro-4H-cyclohepta[b]thiophene-3-carboxamide and N-[3-(aminocarbonyl)-4,5-dimethyl-2-thienyl]-2-furancarboxamide (compounds 1 and 2, respectively) were recently identified to be modestly potent inhibitors of the RNase H activity of HIV-1 and HIV-2 reverse transcriptase (RT). Both compounds shared a 3-CONH2-substituted thiophene ring but were otherwise structurally unrelated, which prevented a precise definition of the pharmacophore. We have therefore examined a larger series of vinylogous ureas carrying amide, amine, and cycloalkane modifications of the thiophene ring of compound 1. While cycloheptane- and cyclohexane-substituted derivatives retained potency, cyclopentane and cyclooctane substitutions eliminated activity. In the presence of a cycloheptane ring, modifying the 2-NH2 or 3-CONH2 functions decreased the potency. With respect to compound 2, vinylogous ureas whose dimethylthiophene ring contained modifications of the 2-NH2 and 3-CONH2 functions were investigated. 2-NH2-modified analogs displayed potency equivalent to or enhanced over that of compound 2, the most active of which, compound 16, reflected intramolecular cyclization of the 2-NH2 and 3-CONH2 groups. Molecular modeling was used to define an inhibitor binding site in the p51 thumb subdomain, suggesting that an interaction with the catalytically conserved His539 of the p66 RNase H domain could underlie inhibition of RNase H activity. Collectively, our data indicate that multiple functional groups of vinylogous ureas contribute to their potencies as RNase H inhibitors. Finally, single-molecule spectroscopy indicates that vinylogous ureas have the property of altering the reverse transcriptase orientation on a model RNA-DNA hybrid mimicking initiation plus-strand DNA synthesis.

Sign in / Sign up

Export Citation Format

Share Document