Suggested mechanisms for Zika virus causing microcephaly: what do the genomes tell us?

摘要: Zika virus (ZIKV) is an emerging human pathogen. Since its arrival in the Western hemisphere, from Africa via Asia, it has become a serious threat to pregnant women, causing microcephaly and other neuropathies developing fetuses. The mechanisms behind these teratogenic effects are unknown, although epidemiological evidence suggests that not associated with original, African lineage of ZIKV. sequences 196 published ZIKV genomes were used assess whether recently proposed mechanistic explanations for supported by molecular level changes may have increased virulence since left Africa. For this we performed phylogenetic, recombination, adaptive evolution tetramer frequency analyses, compared protein presence protease cleavage sites, Pfam domains, glycosylation signal peptides, trans-membrane phosphorylation sites. Recombination events within or between Asian Brazilian lineages observed, likewise there no differences cleavage, peptides domains strains. Retinoic Acid Response Element (RARE) was Genetic adaptation also apparent signatures had undergone major past but stabilized despite subsequent geographic spread, suggesting viral population presently propagates same host species various regions. Evidence selection pressure recognized several amino acid sites lineage, mainly nonstructural proteins, especially NS4B. A number positively selected mutations resulted potential be phosphorylated linage, which their interfere neural fetal development. seems adapted limited hosts, including humans, during increased. Its NS4B, together NS4A, been shown inhibit Akt-mTOR signaling stem cells, key pathway brain We hypothesize positive novel NS4B could Akt mTOR, impairing result risk developmental neuropathies.