Islands of linkage in an ocean of pervasive recombination reveals two-speed evolution of human cytomegalovirus genomes

Human cytomegalovirus (HCMV) infects most of the population worldwide, persisting throughout the host's life in a latent state with periodic episodes of reactivation. While typically asymptomatic, HCMV can cause fatal disease among congenitally infected infants and immunocompromised patients. These clinical issues are compounded by the emergence of antiviral resistance and the absence of an effective vaccine, the development of which is likely complicated by the numerous immune evasins encoded by HCMV to counter the host's adaptive immune responses, a feature that facilitates frequent super-infections. Understanding the evolutionary dynamics of HCMV is essential for the development of effective new drugs and vaccines. By comparing viral genomes from uncultivated or low-passaged clinical samples of diverse origins, we observe evidence of frequent homologous recombination events, both recent and ancient, and no structure of HCMV genetic diversity at the whole-genome scale. Analysis of individual gene-scale loci reveals a striking dichotomy: while most of the genome is highly conserved, recombines essentially freely and has evolved under purifying selection, 21 genes display extreme diversity, structured into distinct genotypes that do not recombine with each other. Most of these hyper-variable genes encode glycoproteins involved in cell entry or escape of host immunity. Evidence that half of them have diverged through episodes of intense positive selection suggests that rapid evolution of hyper-variable loci is likely driven by interactions with host immunity. It appears that this process is enabled by recombination unlinking hyper-variable loci from strongly constrained neighboring sites. It is conceivable that viral mechanisms facilitating super-infection have evolved to promote recombination between diverged genotypes, allowing the virus to continuously diversify at key loci to escape immune detection, while maintaining a genome optimally adapted to its asymptomatic infectious lifecycle

Impact of mating behaviour on the success of malaria control through a single inundative release of transgenic mosquitoes

Transgenic mosquitoes are a potential tool for the control or eradication of insect-vectored diseases. For malaria, one possible strategy relies on the introduction of malaria-refractory transgenes into wild Anopheles mosquito populations that would limit their capacity to transmit the disease. The success of such an approach obviously depends on a variety of factors. By developing a model that integrates both population genetics and epidemiology, we explore how mosquito mating preferences and the cost and efficacy ofrefractoriness affects the long-term prevalence of malaria in humans subsequent to a single generation inundative release of male transgenic mosquitoes. As may be intuitively expected, mating discrimination by wild-type individuals against transgenic ones generally reduces the probability that transgenes be comestably established at a high frequency in mosquito populations. We also show that in circumstances where transgenic individuals exhibit some degree of discrimination against wild-type individuals, this can favour the spread of refractory alleles and lead to a significant reduction in malaria prevalence in the human population (if the efficacy of a dominant refractory mechanism exceeds at least 75%). The existence of such a non-intuitive outcome highlights the practical value of increasing the understanding of Anopheles mating preferences in the wild as a means to harness them in the implementation of population replacement approaches. Potential strategies by which previously described mating preferences of Anopheles gambiae populations could be exploited to manipulate the matechoice of transgenic release stocks are discussed

Consumption of hypoallergenic flour prevents gluten-induced airway inflammation in Brown Norway rats.

Brown Norway rats were immunized with gluten, and then fed a diet containing hypoallergenic fluor or an amino acid mixture. The rats were then made to inhale a solubilized gluten to induce gluten-specific bronchial asthma. The antibody levels in the serum of rats were measured by ELISA, and cell counts were done on cytospin preparations of bronchoalveolar lavage fluid. Body weight was decreased after allergen challenge in rats fed the amino acid mixture but not in rats fed the hypoallergenic flour. Antibody levels in the serum were significantly lower in rats fed hypoallergenic flour than in those fed the amino acid mixture. Differential cell counts in the bronchoalveolar lavage fluid showed that the numbers of eosinophils, lymphocytes, and neutrophils were significantly lower in rats fed the hypoallergenic flour than in those fed the amino acid mixture. These results suggest that hypoallergenic flour actively suppresses the allergic reactions, probably by inducing oral tolerance