Effects of K65R and K65R/M184V Mutations on HIV Reverse Transcriptase Function
Author Information
Author(s): Xu Hong-Tao, Martinez-Cajas Jorge L, Ntemgwa Michel L, Coutsinos Dimitrios, Frankel Fernando A, Brenner Bluma G, Wainberg Mark A
Primary Institution: McGill University AIDS Centre, Lady Davis Institute, Jewish General Hospital, Montreal, Quebec, Canada
Hypothesis
Variations in enzymatic function might be responsible for the higher propensity of K65R to occur in subtype C variants of HIV.
Conclusion
The K65R and K65R+M184V mutations reduce the susceptibility of HIV-1 subtype C to tenofovir diphosphate.
Supporting Evidence
- The K65R mutation leads to decreased susceptibility to NRTIs except zidovudine.
- K65R and K65R+M184V mutations showed impaired efficiency in ssDNA synthesis.
- Both mutations resulted in diminished rates of excision of incorporated nucleotides.
- Subtype C RTs with K65R exhibited lower activity in single-cycle processivity assays.
Takeaway
Some changes in HIV can make it harder for medicine to work. This study looked at how certain changes in the virus affect its ability to be treated.
Methodology
Recombinant subtype C HIV-1 reverse transcriptases were purified and their enzyme activities were measured in cell-free assays.
Limitations
The study did not test the effects of thymidine analog resistance mutations on subtype C RT enzymatic function.
Statistical Information
P-Value
p ≤ 0.01
Statistical Significance
p ≤ 0.01
Digital Object Identifier (DOI)
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