Nucleotide Sequence and Expression of an AIDS-Associated Retrovirus (ARV-2)

Sánchez-Pescador, Ray; Power, Michael D.; Barr, Philip J.; Steimer, Kathelyn S.; Stempien, Michelle M.; Brown-Shimer, Sheryl; Gee, Wendy W.; Renard, A.; Randolph, Anne; Levy, Jay A.; Dina, Dino; Luciw, Paul A.

doi:10.1126/science.2578227

Cited by 700 publications

(305 citation statements)

References 54 publications

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“…The trend was significant in ENV (slope ¼ 20.40 and p ¼ 0.03) but not POL (slope ¼ 20.11 and p ¼ 0.19; figure 2a). This can be explained by stronger evolutionary constraints acting on POL, which plays a key role in nucleic acid replication [55].…”

Section: Results and Discussion (A) Meta-analysis Of Rate Estimates Amentioning

confidence: 99%

Analyses of evolutionary dynamics in viruses are hindered by a time-dependent bias in rate estimates

2014

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Time-scales of viral evolution and emergence have been studied widely, but are often poorly understood. Molecular analyses of viral evolutionary timescales generally rely on estimates of rates of nucleotide substitution, which vary by several orders of magnitude depending on the timeframe of measurement. We analysed data from all major groups of viruses and found a strong negative relationship between estimates of nucleotide substitution rate and evolutionary timescale. Strikingly, this relationship was upheld both within and among diverse groups of viruses. A detailed case study of primate lentiviruses revealed that the combined effects of sequence saturation and purifying selection can explain this time-dependent pattern of rate variation. Therefore, our analyses show that studies of evolutionary time-scales in viruses require a reconsideration of substitution rates as a dynamic, rather than as a static, feature of molecular evolution. Improved modelling of viral evolutionary rates has the potential to change our understanding of virus origins.

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Section: Results and Discussion (A) Meta-analysis Of Rate Estimates Amentioning

confidence: 99%

Analyses of evolutionary dynamics in viruses are hindered by a time-dependent bias in rate estimates

2014

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“…The target monomer sequence, 99 residues in length (SF2 strain) (Sanchez-Pescador et al, 1985), contained L-W amino-n-butyric acid (Aba) as an isosteric replacement for cysteine . BTD (bicyclic turn dipeptide: (3S,6S,9R)-2-oxo-3-t-butyloxycarboxylamino-7-thia-l-aza-bicyclo[4.3.0]nonane-9-carboxylic acid) (Fig.…”

Section: Protein Synthesismentioning

confidence: 99%

Structural engineering of the HIV‐1 protease molecule with a β‐turn mimic of fixed geometry

1993

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An important goal in the de novo design of enzymes is the control of molecular geometry. To this end, an analog of the protease from human immunodeficiency virus 1 (HIV-1 protease) was prepared by total chemical synthesis, containing a constrained, nonpeptidic type 11' 0-turn mimic of predetermined three-dimensional structure.The mimic &turn replaced residues GlyI6,l7 in each subunit of the homodimeric molecule. These residues constitute the central amino acids of two symmetry-related type I' 0-turns in the native, unliganded enzyme. The 0-turn mimic-containing enzyme analog was fully active, possessed the same substrate specificity as the GlyI67l7-containing enzyme, and showed enhanced resistance to thermal inactivation. These results indicate that the precise geometry of the @turn at residues 15-18 in each subunit is not critical for activity, and that replacement of the native sequence with a rigid 0-turn mimic can lead to enhanced protein stability. Finally, the successful incorporation of a fixed element of secondary structure illustrates the potential of a "molecular kit set" approach to protein design and synthesis.

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“…The human immunodeficiency virus type 1 (HIV-1) is a complex retrovirus that contains several auxiliary (nef, vif, vpr, and vpu) [1,2] and two regulatory (tat and rev) genes in addition to the structural genes common to all retroviruses (gag, pol, and env) [3][4][5][6][7][8]. Nef is encoded by an open reading frame located at the 3' end of the viral genome, partially overlapping the 3' long terminal repeat (LTR).…”

Section: Introductionmentioning

confidence: 99%

Human immunodeficiency virus type 1 Nef protein on the cell surface is cytocidal for human CD4+ T cells

et al. 1996

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Nucleotide Sequence and Expression of an AIDS-Associated Retrovirus (ARV-2)

Cited by 700 publications

References 54 publications

Analyses of evolutionary dynamics in viruses are hindered by a time-dependent bias in rate estimates

Analyses of evolutionary dynamics in viruses are hindered by a time-dependent bias in rate estimates

Structural engineering of the HIV‐1 protease molecule with a β‐turn mimic of fixed geometry

Human immunodeficiency virus type 1 Nef protein on the cell surface is cytocidal for human CD4+ T cells

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