Phylogenesys and homology modeling in Zika virus epidemic: food for thought

<p>Zika virus (ZIKV) is an emerging Flavivirus that have recently caused an outbreak in Brazil and rapid spread in several countries. In this study, the consequences of ZIKV evolution on protein recognition by the host immune system have been analyzed. Evolutionary analysis was combined with homology modeling and T-B cells epitope predictions. Two separate clades, the African one with the Uganda sequence, as the most probable ancestor, and the second one containing all the most recent sequences from the equatorial belt were identified. Brazilian strains clustered all together and closely related to the French Polynesia isolates. A strong presence of a negatively selected site in the envelope gene (<i>Env</i>) protein was evidenced, suggesting a probable purging of deleterious polymorphisms in functionally important genes. Our results show relative conservancy of ZIKV sequences when envelope and other non-structural proteins (NS3 and NS5) are analyzed by homology modeling. However, some regions within the consensus sequence of NS5 protein and to a lesser extent in the envelope protein, show localized high mutation frequency corresponding to a considerable alteration in protein stability. In terms of viral immune escape, envelope protein is under a higher selective pressure than NS5 and NS3 proteins for HLA class I and II molecules. Moreover, envelope mutations that are not strictly related to T-cell immune responses are mostly located on the surface of the protein in putative B-cell epitopes, suggesting an important contribution of B cells in the immune response as well.</p

Additional file 1 of MISSEL: a method to identify a large number of small species-specific genomic subsequences and its application to viruses classification

The user guide for MISSEL software, which is a pdf file with all the instructions for the user to run the software. (PDF 891 KB

The maximum clade credibility (MCC) tree of CCHFV S gene sequences.

<p>The branches are coloured on the basis of the most probable location of the descendent nodes (A=Africa, AL=Albania, ASC=Central Asia, BU=Bulgaria, CH=China, G=Greece, KO=Kosovo, MO=Middle East, PA=Pakistan, T=Turkey). The numbers on the internal nodes indicate significant posterior probabilities (pp>0.8), and the scale at the bottom of the tree represents the number of years before the last sampling time (2010). The main geographical clades (genotypes) have been highlighted.</p

Phylogeographical mapping of CCHF S gene sequences .

<p>The bubblegrams show the frequency of gene flows (migrations) to/from ten European countries (same code as that used in Figure 1) . The surface of each circle is proportional to the percentage of observed migrations in the ML genealogy. The migrations were inferred using a modified version of the Slatkin and Maddison algorithm.</p

Significant non-zero CCHFV migration rates worldwide.

<p>Rates supported by a BF of >3 are highlighted: the relative strength of the support is indicated by the colour of the lines (from dark red = weak to light red = strong). Dotted lines indicate non-significant linkages. The map was reconstructed using SPREAD (see Methods). The numbers indicate the mean estimated year in which the virus entered the area. </p

Significant non-zero HBV-D migration rates worldwide.

<p>Only the rates supported by a BF of >6 are shown. The relative strength of the support is indicated by the colour of the lines (from dark red = weak to light red = strong). The map was reconstructed using SPREAD (see <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0037198#s2" target="_blank">Methods</a>).</p

The maximum clade credibility (MCC) tree of HBV-D P gene sequences.

<p>The branches are coloured on the basis of the most probable location state of the descendent nodes (see colour codes in upper left inset). The numbers on the internal nodes represent posterior probabilities, and the scale at the bottom of the tree represents the years before the last sampling time (2007). The clades corresponding to the main HBV-D subgenotypes (D1, D2, D3, D5, D7) are highlighted.</p

tMRCAs and locations of the main clades.

1<p>tMRCA: Time of the most recent common ancestor.</p>2<p>95%HPD U 95%: Highest Posterior Density Upper.</p>3<p>95%HPD U 95%: Highest Posterior Density Lower.</p>4<p>pp: posterior probability.</p><p>Time of the most recent common ancestor (tMRCA) estimates with credibility intervals (95%HPD) with corresponding years and most probable locations with state posterior probabilities (pp) of the main clades observed in the MCC tree of <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0037198#pone-0037198-g002" target="_blank">Figure 2</a>.</p

Amino acid sites under positive selection in gp120 V3, C3 and C4 regions of HIV-1 clade C variants from patients at different disease stages.

<p><b>ES  =  Early disease Stage; CS  =  Chronic disease Stage; LS  =  Late disease Stage.</b></p

V3–V5 phylogenetic tree of HIV-1 strains from 72 HIV-1-infected patients in South Africa and Swaziland.

<p>Tree was rooted by using the midpoint rooting method. Scale bar at the bottom indicates 7% nucleotide substitutions per site. The asterisk along a branch represents the bootstrap value (significant statistical support) >70% and p<0.001 in the zero-branch-length test. Years of collection of samples are color-highlighted: 2005 in blue, 2006 in red and 2007 in green. Country where sample collection was performed: SW  =  Swaziland; SA  =  South Africa.</p