Sources of genetic variation in arenaviridae - theoretical models and evidence in nature

GHIRINGHELLI, P.D.; GOÑI, S.E.; LOZANO, M.E.; POSIK, D.M.; ROMANOWSKI, V.

Paris

Congreso; XIIth International Congress of Virology, International Union of Microbiological Societies; 2002

International Union of Microbiological Societies

Arenaviruses have a bipartite ssRNA genome with an ambisense coding strategy. The virions are enveloped and package non-equimolar amounts of each genomic RNA species (L and S RNAs).  Genetic reassortment in dually infected cells has been recognized as a major source for genetic variation; more recently, evidence has emerged that suggests the possibility of RNA recombination. Some arenaviruses have been recognized as etiological agents for serious human diseases. The common feature of these diseases is their restricted geographical distribution and the emerging character of the first outbreaks.  The main causes for the emergence of new viral diseases include changes in the ecology, human activity and viral genome variation.  Here we present alternative models for molecular recombination based upon the analysis of previously reported and recently obtained arenavirus RNA sequences. The molecular mechanisms that lead to the formation of recombinant RNA species may include template-switching, primer-alignment-and-extension and transesterification.  Whitewater Arroyo (isolated in the US) and Rio Carcarañá Virus (recently isolated in Argentina) provide evidence for RNA recombination between New World Arenaviruses of different lineages in nature. This and other genetic variation mechanisms, as well as the use of sensitive detection and analysis methods, indicate that the number of members of the Arenaviridae will probably continue to grow. Finally, it is possible to speculate that emergence or re-emergence of human infections could be minimized with the help of careful molecular-epidemiological surveillance programs.