Title |
Turning up the volume on mutational pressure: Is more of a good thing always better? (A case study of HIV-1 Vif and APOBEC3)
|
---|---|
Published in |
Retrovirology, March 2008
|
DOI | 10.1186/1742-4690-5-26 |
Pubmed ID | |
Authors |
Satish K Pillai, Joseph K Wong, Jason D Barbour |
Abstract |
APOBEC3G and APOBEC3F are human cytidine deaminases that serve as innate antiviral defense mechanisms primarily by introducing C-to-U changes in the minus strand DNA of retroviruses during replication (resulting in G-to-A mutations in the genomic sense strand sequence). The HIV-1 Vif protein counteracts this defense by promoting the proteolytic degradation of APOBEC3G and APOBEC3F in the host cell. In the absence of Vif expression, APOBEC3 is incorporated into HIV-1 virions and the viral genome undergoes extensive G-to-A mutation, or "hypermutation", typically rendering it non-viable within a single replicative cycle. Consequently, Vif is emerging as an attractive target for pharmacological intervention and therapeutic vaccination. Although a highly effective Vif inhibitor may result in mutational meltdown of the viral quasispecies, a partially effective Vif inhibitor may accelerate the evolution of drug resistance and immune escape due to the codon structure and recombinogenic nature of HIV-1. This hypothesis rests on two principal assumptions which are supported by experimental evidence: a) there is a dose response between intracellular APOBEC concentration and degree of viral hypermutation, and, b) HIV-1 can tolerate an elevated mutation rate, and a true error or extinction threshold is as yet undetermined. Rigorous testing of this hypothesis will have timely and critical implications for the therapeutic management of HIV/AIDS, and delve into the complexities underlying the induction of lethal mutagenesis in a viral pathogen. |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
Brazil | 3 | 4% |
United States | 3 | 4% |
France | 2 | 3% |
United Kingdom | 1 | 1% |
South Africa | 1 | 1% |
Japan | 1 | 1% |
Spain | 1 | 1% |
Unknown | 56 | 82% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Researcher | 20 | 29% |
Student > Ph. D. Student | 11 | 16% |
Student > Bachelor | 10 | 15% |
Student > Doctoral Student | 6 | 9% |
Professor | 4 | 6% |
Other | 11 | 16% |
Unknown | 6 | 9% |
Readers by discipline | Count | As % |
---|---|---|
Agricultural and Biological Sciences | 32 | 47% |
Biochemistry, Genetics and Molecular Biology | 11 | 16% |
Medicine and Dentistry | 9 | 13% |
Chemical Engineering | 2 | 3% |
Immunology and Microbiology | 2 | 3% |
Other | 7 | 10% |
Unknown | 5 | 7% |