Viral phenotype and fitness.
ABSTRACT The fitness is a parameter defining the replicative adaptation of an organism to its environment. Recently, the HIV research field has shown renewed interest in the replicative capacity of human immunodeficiency virus type 1 (HIV-1) due to the potential impact of ex vivo viral fitness on population size, drug resistance, and disease progression. In the absence of antiretroviral therapy, strains containing drug-resistance mutations have a reduced fitness compared to the wild-type (wt) quasispecies within the population. Therefore, selective pressure of drug therapy leads to dramatic shifts in the quasispecies distribution and fitness of those mutants with decreased sensitivity to the respective antiretrovirals. Even if the presence of drug resistance mutations can decrease the viral fitness and explain a sustained CD4+T cell count in presence of high viral load, the current treatment guidelines advocate a switch in antiretroviral treatment regimens following the emergence of primary drug resistant mutations and possibly prior to selection of compensatory changes.
01/2012; , ISBN: 978-953-307-871-7
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ABSTRACT: Over the last fifteen years there have been five pandemics of norovirus (NoV) associated gastroenteritis, and the period of stasis between each pandemic has been progressively shortening. NoV is classified into five genogroups, which can be further classified into 25 or more different human NoV genotypes; however, only one, genogroup II genotype 4 (GII.4), is associated with pandemics. Hence, GII.4 viruses have both a higher frequency in the host population and greater epidemiological fitness. The aim of this study was to investigate if the accuracy and rate of replication are contributing to the increased epidemiological fitness of the GII.4 strains. The replication and mutation rates were determined using in vitro RNA dependent RNA polymerase (RdRp) assays, and rates of evolution were determined by bioinformatics. GII.4 strains were compared to the second most reported genotype, recombinant GII.b/GII.3, the rarely detected GII.3 and GII.7 and as a control, hepatitis C virus (HCV). The predominant GII.4 strains had a higher mutation rate and rate of evolution compared to the less frequently detected GII.b, GII.3 and GII.7 strains. Furthermore, the GII.4 lineage had on average a 1.7-fold higher rate of evolution within the capsid sequence and a greater number of non-synonymous changes compared to other NoVs, supporting the theory that it is undergoing antigenic drift at a faster rate. Interestingly, the non-synonymous mutations for all three NoV genotypes were localised to common structural residues in the capsid, indicating that these sites are likely to be under immune selection. This study supports the hypothesis that the ability of the virus to generate genetic diversity is vital for viral fitness.PLoS Pathogens 01/2010; 6(3):e1000831. · 9.13 Impact Factor