TABLE 3.
Comparative analysis of biochemical and virology data
| HIV-1 subtype | Integrase phenotype | Extent of INSTI susceptibility (FC relative to WT)a |
% integration activityb |
||||||
|---|---|---|---|---|---|---|---|---|---|
| DTG |
RAL |
EVG |
EE | RC | |||||
| Cell free | Cell culture | Cell free | Cell culture | Cell free | Cell culture | ||||
| CRF02_AG | WT | − | 100 | 100 | |||||
| H51Y | − | − | ++ | − | − | + | 117 | 69 | |
| G118R | ++ | +++ | +++ | +++ | ++ | ++ | 49.1 | 8 | |
| E138K | ++ | − | − | − | +++ | − | 86.5 | 91 | |
| H51Y/G118R | + | ND | − | ND | − | ND | 38.1 | ND | |
| G118R/E138K | − | +++ | ++ | +++ | ++ | ++ | 64.9 | 32 | |
| B | WT | − | − | − | − | − | − | 100 | 100 |
| H51Y | ++ | − | − | − | ++ | + | ND | 89 | |
| G118R | ++ | ++ | ++ | +++ | +++ | +++ | 54.7 | 30 | |
| E138K | + | − | ++ | − | − | − | ND | 77 | |
| H51Y/G118R | ++ | ND | ++ | ND | ++ | ND | 82.3 | ND | |
| G118R/E138K | ++ | + | +++ | − | + | 46.8 | 43 | ||
| C | WT | ND | − | ND | − | ND | 100 | ND | |
| H51Y | ++ | ND | +++ | ND | ++ | ND | 132 | ND | |
| G118R | + | ND | + | ND | + | ND | 96.4 | ND | |
| E138K | − | ND | − | ND | − | ND | 70.0 | ND | |
| H51Y/G118R | ++ | ND | + | ND | + | ND | 32.2 | ND | |
| G118R/E138K | ++ | ND | + | ND | − | ND | 93.1 | ND | |
Cell culture experiments tend to yield higher FC values than do cell-free assays (>3) (16). Susceptibility rankings of FC for cell-free experiments are as follows: −, 0 to <1.5; +, 1.5 to <2.5; ++, 2.5 to <4.0; +++, ≥4.0. In cell culture experiments, susceptibility rankings are as follows: −, 0 to <2.0; +, 2.0 to <5.0; ++, 5.0 to <10.0; +++, ≥10.0.
In the cell, 3′ processing is the rate-limiting step for integration (7); therefore, we either calculated the overall integration efficiency by multiplication of the enzyme efficiency (EE) values for 3′ processing and strand transfer (if the enzyme efficiency for 3′ processing was higher than the strand transfer efficiency) or retained the enzyme efficiency for 3′ processing (if the efficiency of 3′ processing was much lower than the strand transfer efficiency). ND, not determined; RC, replication capacity.