Virus Evolution as a Tool to Study HIV-1 Biology

Mutational analysis of the viral genome is frequently used to study the role of sequence or structural elements in HIV-1 replication. Many laboratories that use this approach have occasionally come across revertant viruses that overcome an introduced defect either by restoration of the original sequence or by the introduction of additional mutations in the viral genome. Similarly, replication of a wild type virus under selective pressure, due to the presence of inhibitors or due to specific culture settings, may result in the appearance of evolved variants that replicate more efficiently under the applied conditions. We have developed in vitro HIV-1 evolution from an anecdotal event to a systematic research tool to study different aspects of the viral replication cycle. In this manuscript, we will briefly review the method of forced virus evolution to study HIV-1 biology and provide several examples that illustrate the power of this method, as it frequently yielded interesting and unexpected information about the mechanism of virus replication.