Genetic variability: The key problem in the prevention and therapy of RNA‐based virus infections

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Abstract
Despite extraordinary progress that has recently been made in biomedical sciences, viral infectious diseases still remain one of the most serious world health problems. Among the different types of viruses, those using RNA as their genetic material (RNA viruses and retroviruses) are especially dangerous. At present there is no medicine allowing an effective treatment of RNA‐based virus infections. Many RNA viruses and retroviruses need only a few weeks to escape immune response or to produce drug‐resistant mutants. This seems to be the obvious consequence of the unusual genetic variability of RNA‐based viruses. An individual virus does not form a homogenous population but rather a set of similar but not identical variants. In consequence, RNA‐based viruses can easily adapt to environmental changes, also those resulting from immune system response or therapy. The modifications identified within viral genes can be divided into two groups: point mutations and complex genome rearrangements. The former arises mainly during error‐prone replication, whereas RNA recombination and generic reassortment are responsible for the latter. This article shortly describes major strategies used to control virus infections. Then, it presents the various mechanisms generating the genetic diversity of RNA‐based viruses, which are most probably the main cause of clinical problems. © 2003 Wiley Periodicals, Inc. Med Res Rev, 23, No. 4, 488–518, 2003