19 research outputs found
Bayesian Skyline plot depicting GBV-C effective population size in each HIV-infected individual.
<p>Recombinant sequences were excluded from the analysis. (A) Viruses in these nine individuals showed three phase growth: stationary phase, followed by sudden increase and stable population size thereafter. (B) Viral population in QC_5 was relatively stable with a sign of recent increase. The substitution rate 3.9×10<sup>−4</sup>sub/site/year that had been previously reported for E gene of GBV-C (Nakao et al., 1997) was used for TMRCA estimation.</p
Likelihood ratio tests (LRTs) for positive selection.
<p>LRTs revealed none of the amino acid sites of E2 in each patient was under positive selection at p<0.05.</p><p>2<i>Δl</i>: Differences between the likelihood scores of null (M7) and alternative model (M8).</p><p>The p-values were calculated with degrees of freedom = 2.</p><p>Null model (M7) that assumes neutral evolution was compared with the model (M8) that assumes positive selection.</p
Evidence for Within-Host Genetic Recombination among the Human Pegiviral Strains in HIV Infected Subjects
<div><p>The non-pathogenic Human Pegivirus (HPgV, formerly GBV-C/HGV), the most prevalent RNA virus worldwide, is known to be associated with reduced morbidity and mortality in HIV-infected individuals. Although previous studies documented its ubiquity and important role in HIV-infected individuals, little is known about the underlying genetic mechanisms that maintain high genetic diversity of HPgV within the HIV-infected individuals. To assess the within-host genetic diversity of HPgV and forces that maintain such diversity within the co-infected hosts, we performed phylogenetic analyses taking into account 229 HPgV partial E1-E2 clonal sequences representing 15 male and 8 female co-infected HIV patients from Hubei province of central China. Our results revealed the presence of eleven strongly supported clades. While nine clades belonged to genotype 3, two clades belonged to genotype 2. Additionally, four clades that belonged to genotype 3 exhibited inter-clade recombination events. The presence of clonal sequences representing multiple clades within the HIV-infected individual provided the evidence of co-circulation of HPgV strains across the region. Of the 23 patients, six patients (i.e., five males and one female) were detected to have HPgV recombinant sequences. Our results also revealed that while male patients shared the viral strains with other patients, viral strains from the female patients had restricted dispersal. Taken together, the present study revealed that multiple infections with divergent HPgV viral strains may have caused within-host genetic recombination, predominantly in male patients, and therefore, could be the major driver in shaping genetic diversity of HPgV.</p></div
Phylogenetic networks of HPgV E1-E2 segments.
<p>(<b>A</b>) A split network, including all sequences, was first constructed. The sequences clustered in eleven clades designated 1 to 11. The outliers are classified as putative intra-subtype recombinants (in red) or a novel clade (in black). (<b>B</b>) Sequences inferring conflicting phylogenetic signals were excluded (recombinant candidates) were removed, and a new split network was constructed.</p
Detection of recombination in complete E2 sequences by six different methods.
a<p>Breakpoint Positions Relative to U36380.</p><p>NS: Not significant at p = 0.0005.</p
Geographic origin of samples in Hubei Province, China.
<p>Geographic origin of samples in Hubei Province, China.</p
Primers used for GBV-C detection and genotyping.
a<p>Mixed base code Y was used for the mixture of C and T; W for A and T; R for A and G; H for A, T and C; V for G, A and C; D for G, A and T.</p>b<p>Nucleotide positions are numbered as for AF121950.</p
Nucleotide diversity of each patient.
<p>The bar plots for each individual (<b>A</b>) and patient-specific group (<b>B</b>) show a relatively higher intra-host nucleotide diversity in patients detected with recombination sequences (black) or/and infected with multiple variants (grey) than other patients (white). Nucleotide diversity was evaluated regardless of recombination.</p
Infection route, therapy, number of clonal sequences, nucleotide diversity, mean nucleotide pairwise differences, mismatch distribution p-value, neutrality test (Tajimas'D and Fu's F), the nonsynonymous to synonymous substitutions, and the estimated time when each patient might have infected with GBV-C were mentioned.
<p>n: Number of sequences.</p><p>π: Nucleotide diversity.</p><p>d: Mean Paidwise difference.</p><p>P: P-value.</p><p>HPD: Highest Posterior Density.</p><p>ω: Rate of Nonsynonymous (dN) to the Rate of Synonymous (dS) substitutions.</p
Distribution of the pairwise nucleotide sequence differences within each patient.
<p>(A) Eight patients showed unimodal distribution indicating sudden population expansion of GBV-C in respective individuals. (B) Patient JZ_26 virus showed an L-shape distribution. The L-shape distribution in JZ_26 was sign of post bottleneck population expansion, (C) Patient QC_5 showed multiple peaks. The hypothesis of sudden population expansion for each patient could not be rejected (p>0.05, <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0048417#pone-0048417-t003" target="_blank">Table 3</a>). The observed and simulated pairwise differences are shown in dotted and solid lines, respectively. Recombinant sequences were excluded from the analysis.</p