|
Basic Characteristics of Mutations
|
|
Mutation Site
|
K103N |
|
Mutation Site Sentence
|
In the absence of any ARV drugs, the PBMCs accumulated drug resistance mutations. The highest levels of mutations in the proviral DNA were at K103N and G190E, conferring resistance to EFV (Fig. 3C). |
|
Mutation Level
|
Amino acid level |
|
Mutation Type
|
Nonsynonymous substitution |
|
Gene/Protein/Region
|
RT |
|
Standardized Encoding Gene
|
gag-pol:155348
|
|
Genotype/Subtype
|
HIV-1 |
|
Viral Reference
|
-
|
|
Functional Impact and Mechanisms
|
|
Disease
|
Cell line
|
|
Immune
|
- |
|
Target Gene
|
-
|
|
Clinical and Epidemiological Correlations
|
|
Clinical Information
|
- |
|
Treatment
|
NNRTIs |
|
Location
|
- |
|
Literature Information
|
|
PMID
|
31025011
|
|
Title
|
Role of co-expressed APOBEC3F and APOBEC3G in inducing HIV-1 drug resistance
|
|
Author
|
Mohammadzadeh N,Love RP,Gibson R,Arts EJ,Poon AFY,Chelico L
|
|
Journal
|
Heliyon
|
|
Journal Info
|
2019 Apr 16;5(4):e01498
|
|
Abstract
|
The APOBEC3 enzymes can induce mutagenesis of HIV-1 proviral DNA through the deamination of cytosine. HIV-1 overcomes this restriction through the viral protein Vif that induces APOBEC3 proteasomal degradation. Within this dynamic host-pathogen relationship, the APOBEC3 enzymes have been found to be beneficial, neutral, or detrimental to HIV-1 biology. Here, we assessed the ability of co-expressed APOBEC3F and APOBEC3G to induce HIV-1 resistance to antiviral drugs. We found that co-expression of APOBEC3F and APOBEC3G enabled partial resistance of APOBEC3F to Vif-mediated degradation with a corresponding increase in APOBEC3F-induced deaminations in the presence of Vif, in addition to APOBEC3G-induced deaminations. We recovered HIV-1 drug resistant variants resulting from APOBEC3-induced mutagenesis, but these variants were less able to replicate than drug resistant viruses derived from RT-induced mutations alone. The data support a model in which APOBEC3 enzymes cooperate to restrict HIV-1, promoting viral inactivation over evolution to drug resistance.
|
|
Sequence Data
|
-
|