Predicting human immunodeficiency virus protease cleavage sites in nonlinear projection space

2010 ◽  
Vol 339 (1-2) ◽  
pp. 127-133 ◽  
Author(s):  
Xuehua Li ◽  
Hongli Hu ◽  
Lan Shu
Keyword(s):  
Human Immunodeficiency Virus ◽  
Cleavage Sites ◽  
Human Immunodeficiency Virus Protease ◽  
Protease Cleavage ◽  
Nonlinear Projection ◽  
Immunodeficiency Virus ◽  
Protease Cleavage Sites

scholarly journals Human Immunodeficiency Virus Type 1 Protease Cleavage Site Mutations Associated with Protease Inhibitor Cross-Resistance Selected by Indinavir, Ritonavir, and/or Saquinavir

2001 ◽  
Vol 75 (2) ◽  
pp. 589-594 ◽  
Author(s):  
Hélène C. F. Côté ◽  
Zabrina L. Brumme ◽  
P. Richard Harrigan
Keyword(s):  
Human Immunodeficiency Virus ◽  
Protease Inhibitor ◽  
Cleavage Site ◽  
Cross Resistance ◽  
Cleavage Sites ◽  
Protease Cleavage ◽  
Immunodeficiency Virus ◽  
Before And After ◽  
Protease Cleavage Sites

ABSTRACT We examined the prevalence of cleavage site mutations, both within and outside the gag region, in 28 protease inhibitor (PI) cross-resistant patients treated with indinavir, ritonavir, and/or saquinavir compared to control patients treated with reverse transcriptase inhibitors. Three human immunodeficiency virus protease cleavage sites within gag (p2/NC, NC/p1, and NC/TFP) showed considerable in vivo evolution before and after therapy with indinavir, ritonavir, and/or saquinavir. Another gag cleavage site (p1/p6 gag ) showed a trend compared to matched controls. The other eight recognized cleavage sites showed relatively little difference between PI-resistant cases and controls. An A→V substitution at the P2 position of the NC/p1 and NC/TFP cleavage sites was the most common (29%) change selected by the PIs used in this study.

scholarly journals Variability at Human Immunodeficiency Virus Type 1 Subtype C Protease Cleavage Sites: an Indication of Viral Fitness?

2003 ◽  
Vol 77 (17) ◽  
pp. 9422-9430 ◽  
Author(s):  
Tulio de Oliveira ◽  
Susan Engelbrecht ◽  
Estrelita Janse van Rensburg ◽  
Michelle Gordon ◽  
Karen Bishop ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Human Immunodeficiency Virus Type ◽  
Cleavage Site ◽  
Cleavage Sites ◽  
Subtype C ◽  
Protease Cleavage ◽  
Immunodeficiency Virus ◽  
Protease Cleavage Sites ◽  
Hiv 1

ABSTRACT Naturally occurring polymorphisms in the protease of human immunodeficiency virus type 1 (HIV-1) subtype C would be expected to lead to adaptive (compensatory) changes in protease cleavage sites. To test this hypothesis, we examined the prevalences and patterns of cleavage site polymorphisms in the Gag, Gag-Pol, and Nef cleavage sites of C compared to those in non-C subtypes. Codon-based maximum-likelihood methods were used to assess the natural selection and evolutionary history of individual cleavage sites. Seven cleavage sites (p17/p24, p24/p2, NC/p1, NC/TFP, PR/RT, RT/p66, and p66/IN) were well conserved over time and in all HIV-1 subtypes. One site (p1/p6 gag ) exhibited moderate variation, and four sites (p2/NC, TFP/p6 pol , p6 pol /PR, and Nef) were highly variable, both within and between subtypes. Three of the variable sites are known to be major determinants of polyprotein processing and virion production. P2/NC controls the rate and order of cleavage, p6 gag is an important phosphoprotein required for virion release, and TFP/p6 pol , a novel cleavage site in the transframe domain, influences the specificity of Gag-Pol processing and the activation of protease. Overall, 58.3% of the 12 HIV-1 cleavage sites were significantly more diverse in C than in B viruses. When analyzed as a single concatenated fragment of 360 bp, 96.0% of group M cleavage site sequences fell into subtype-specific phylogenetic clusters, suggesting that they coevolved with the virus. Natural variation at C cleavage sites may play an important role, not only in regulation of the viral cycle but also in disease progression and response to therapy.

Distorted Key Theory and its Implication for Drug Development

2020 ◽  
Vol 17 (4) ◽  
pp. 311-323 ◽  
Author(s):  
Kuo-Chen Chou
Keyword(s):  
Human Immunodeficiency Virus ◽  
Severe Acute Respiratory Syndrome ◽  
Drug Development ◽  
Cleavage Sites ◽  
Protein Cleavage ◽  
Peptide Drugs ◽  
Human Immunodeficiency Virus Protease ◽  
Immunodeficiency Virus

During the last three decades or so, many efforts have been made to study the protein cleavage sites by some disease-causing enzyme, such as HIV (Human Immunodeficiency Virus) protease and SARS (Severe Acute Respiratory Syndrome) coronavirus main proteinase. It has become increasingly clear viathis mini-review that the motivation driving the aforementioned studies is quite wise, and that the results acquired through these studies are very rewarding, particularly for developing peptide drugs.

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