TY - JOUR
T1 - HIV-1 evolution: frustrating therapies, but disclosing molecular mechanisms
AU - Das, Atze T.
AU - Berkhout, Ben
PY - 2010
Y1 - 2010
N2 - Replication of HIV-1 under selective pressure frequently results in the evolution of virus variants that replicate more efficiently under the applied conditions. For example, in patients on antiretroviral therapy, such evolution can result in variants that are resistant to the HIV-1 inhibitors, thus frustrating the therapy. On the other hand, virus evolution can help us to understand the molecular mechanisms that underlie HIV-1 replication. For example, evolution of a defective virus mutant can result in variants that overcome the introduced defect by restoration of the original sequence or by the introduction of additional mutations in the viral genome. Analysis of the evolution pathway can reveal the requirements of the element under study and help to understand its function. Analysis of the escape routes may generate new insight in the viral life cycle and result in the identification of unexpected biological mechanisms. We have developed in vitro HIV-1 evolution into a systematic research tool that allows the study of different aspects of the viral replication cycle. We will briefly review this method of forced virus evolution and provide several examples that illustrate the power of this approach
AB - Replication of HIV-1 under selective pressure frequently results in the evolution of virus variants that replicate more efficiently under the applied conditions. For example, in patients on antiretroviral therapy, such evolution can result in variants that are resistant to the HIV-1 inhibitors, thus frustrating the therapy. On the other hand, virus evolution can help us to understand the molecular mechanisms that underlie HIV-1 replication. For example, evolution of a defective virus mutant can result in variants that overcome the introduced defect by restoration of the original sequence or by the introduction of additional mutations in the viral genome. Analysis of the evolution pathway can reveal the requirements of the element under study and help to understand its function. Analysis of the escape routes may generate new insight in the viral life cycle and result in the identification of unexpected biological mechanisms. We have developed in vitro HIV-1 evolution into a systematic research tool that allows the study of different aspects of the viral replication cycle. We will briefly review this method of forced virus evolution and provide several examples that illustrate the power of this approach
U2 - https://doi.org/10.1098/rstb.2010.0072
DO - https://doi.org/10.1098/rstb.2010.0072
M3 - Review article
C2 - 20478891
SN - 0962-8436
VL - 365
SP - 1965
EP - 1973
JO - Philosophical transactions of the Royal Society of London. Series B, Biological sciences
JF - Philosophical transactions of the Royal Society of London. Series B, Biological sciences
IS - 1548
ER -