Global dynamics of delayed CHIKV infection model with multitarget cells
JOURNAL OF APPLIED MATHEMATICS AND COMPUTING
Authors: Elaiw, Ahmed M.; Alade, Taofeek O.; Alsulami, Saud M.
We propose a latent chikungunya viral infection model with multitarget cells and saturated incidence rate. The model is an (3n+2)-dimensional system of nonlinear delay differential equations (DDEs) that describes the population dynamics of CHIKV, n categories of uninfected target cells, n categories of infected cells and antibodies. The model is incorporated by intracellular discrete or distributed time delays. The qualitative behavior of the model is studied. We investigate the global stability of the equilibria of the models by using direct Lyapunov method. The effect of the time delay on the stability of the equilibria has also been illustrated by numerical simulations.
RNA recombination at Chikungunya virus 3'UTR as an evolutionary mechanism that provides adaptability
Authors: Filomatori, Claudia, V; Bardossy, Eugenia S.; Merwaiss, Fernando; Suzuki, Yasutsugu; Henrion, Annabelle; Saleh, Maria Carla; Alvarez, Diego E.
The potential of RNA viruses to adapt to new environments relies on their ability to introduce changes in their genomes, which has resulted in the recent expansion of re-emergent viruses. Chikungunya virus is an important human pathogen transmitted by mosquitoes that, after 60 years of exclusive circulation in Asia and Africa, has rapidly spread in Europe and the Americas. Here, we examined the evolution of CHIKV in different hosts and uncovered host-specific requirements of the CHIKV 3'UTR. Sequence repeats are conserved at the CHIKV 3'UTR but vary in copy number among viral lineages. We found that these blocks of repeated sequences favor RNA recombination processes through copy-choice mechanism that acts concertedly with viral selection, determining the emergence of new viral variants. Functional analyses using a panel of mutant viruses indicated that opposite selective pressures in mosquito and mammalian cells impose a fitness cost during transmission that is alleviated by recombination guided by sequence repeats. Indeed, drastic changes in the frequency of viral variants with different numbers of repeats were detected during host switch. We propose that RNA recombination accelerates CHIKV adaptability, allowing the virus to overcome genetic bottlenecks within the mosquito host. These studies highlight the role of 3'UTR plasticity on CHIKV evolution, providing a new paradigm to explain the significance of sequence repetitions. Author summary An emergent virus is a virus that has adapted to new hosts or environments through changes in its viral genome. Using as model chikungunya virus, which had explosively spread in the Americas and Europe during the last decade, we studied viral adaptability to mosquito and mammalian hosts. Natural isolates from recent outbreaks display highly different 3'UTRs, which result in different fitness in mosquito cells. Importantly, drastic changes in viral populations occur when the virus jumps between hosts, with different viral variants being positively and negatively selected according to fitness parameters. Frequent events of RNA recombination, in which the viral polymerase switches templates during RNA synthesis, were observed at the viral 3'UTR. RNA recombination explains the high plasticity of this part of the genome and the subsequent emergence of new viral variants that allows the virus to replicate in disparate systems. Our findings support a new model where viral diversity generated by RNA recombination is a potent viral strategy to overcome the fitness barriers imposed during host switching.