TABLE 5.
Summary of impacts of amino acid substitutions in protease on TPV's protease dimerization inhibition and anti-HIV activity
| Genetic background | Reduction of TPV's activity to inhibit | Amino acid substitution in PR |
|||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| L24I | L24 M | L33I | L33F | E34D | K45I | I54V | L63P | A71V | V82L | V82T | I54V/V82T | ||
| cHIVNL4-3 | Protease dimerization | − | + | + | + | + | − | − | − | − | − | − | − |
| HIV replication | Ea | E | − | − | NDb | ND | − | ND | ND | − | − | − | |
| cHIVB | Protease dimerization | ND | ND | + | ND | ND | ND | − | ND | ND | ND | − | − |
| HIV replication | ND | ND | +c | ND | ND | ND | + | ND | ND | ND | + | + | |
| cHIVC | Protease dimerization | ND | ND | ND | ND | ND | ND | ND | ND | ND | ND | ND | ND |
| HIV replication | ND | + | ND | ND | ND | ND | ND | ND | ND | ND | + | ND | |
a
E, TPV's activity to inhibit HIV replication was enhanced with certain genetic backgrounds.
b
ND, not determined.
c
When the L33I mutation exists with the genetic background of cHIVB carrying I54V or I54V/V82T, L33I reduces the antiviral activity of TPV.