Interferon lambda 4 impacts the genetic diversity of hepatitis C virus.

Hepatitis C virus (HCV) is a highly variable pathogen that frequently establishes chronic infection. This genetic variability is affected by the adaptive immune response but the contribution of other host factors is unclear. Here, we examined the role played by interferon lambda-4 (IFN-λ4) on HCV diversity; IFN-λ4 plays a crucial role in spontaneous clearance or establishment of chronicity following acute infection. We performed viral genome-wide association studies using human and viral data from 485 patients of white ancestry infected with HCV genotype 3a. We demonstrate that combinations of host genetic variants, which determine IFN-λ4 protein production and activity, influence amino acid variation across the viral polyprotein - not restricted to specific viral proteins or HLA restricted epitopes - and modulate viral load. We also observed an association with viral di-nucleotide proportions. These results support a direct role for IFN-λ4 in exerting selective pressure across the viral genome, possibly by a novel mechanism.

Are prorocentroid dinoflagellates monophyletic? A study of 25 species based on nuclear and mitochondrial genes.

The dinoflagellate sub-class Prorocentrophycidae has a distinct morphology, lacking the typical dinoflagellate cell structure of a clear cingulum and sulcus. It includes species that produce the toxin okadaic acid. Despite its uniqueness, the group has been found polyphyletic in some previous molecular phylogenetic studies. We have re-investigated the phylogeny of this sub-class by culturing and sequencing new strains, comparing sequences from three genes, the mitochondrial cytochrome c oxidase subunit 1 (cox 1) and the nuclear large and small subunit rRNA (LSU and SSU) encoding genes. We analyzed sequences from twenty-five named and two still undescribed species of Prorocentrophycidae. We used newly recognized features of the secondary structure to align regions of the LSU rRNA. The phylogeny based on cox 1 provided the most well-supported tree and showed strong support for the monophyly of prorocentroid dinoflagellates, while the LSU phylogeny was inconclusive. As in previous studies, phylogeny based on SSU shows the group to appear paraphyletic, however, support values were low. Two strongly supported sub-clades were consistently identified. Benthic and planktonic modes appear to have evolved on multiple occasions within both clades of Prorocentriphycidae. The capability to synthesize toxins appears to have arisen early in prorocentroid evolution and, in particular, okadaic acid synthesis is present in some, but not all, members of Clade 2. The D2a region of the LSU rRNA appears to have developed a deletion in three definable steps during prorocentroid evolution. While the phylogenies inferred from the three genes were not congruent, our results give reserved support to the monophyly of the group.