Quantitative differences between intra-host HCV populations from persons with recently established and persistent infections

Abstract

Detection of incident hepatitis C virus (HCV) infections is crucial for identification of outbreaks and development of public health interventions. However, there is no single diagnostic assay for distinguishing recent and persistent HCV infections. HCV exists in each infected host as a heterogeneous population of genomic variants, whose evolutionary dynamics remain incompletely understood. Genetic analysis of such viral populations can be applied to the detection of incident HCV infections and used to understand intra-host viral evolution. We studied intra-host HCV populations sampled using next-generation sequencing from 98 recently and 256 persistently infected individuals. Genetic structure of the populations was evaluated using 245,878 viral sequences from these individuals and a set of selected features measuring their diversity, topological structure, complexity, strength of selection, epistasis, evolutionary dynamics, and physico-chemical properties. Distributions of the viral population features differ significantly between recent and persistent infections. A general increase in viral genetic diversity from recent to persistent infections is frequently accompanied by decline in genomic complexity and increase in structuredness of the HCV population, likely reflecting a high level of intra-host adaptation at later stages of infection. Using these findings, we developed a machine learning classifier for the infection staging, which yielded a detection accuracy of 95.22 per cent, thus providing a higher accuracy than other genomic-based models. The detection of a strong association between several HCV genetic factors and stages of infection suggests that intra-host HCV population develops in a complex but regular and predictable manner in the course of infection. The proposed models may serve as a foundation of cyber-molecular assays for staging infection, which could potentially complement and/or substitute standard laboratory assays.

Intra-host evolutionary dynamics of the hepatitis C virus among people who inject drugs

“…Nevertheless, the results from this study suggest that if the goal of a particular research project is to identify recent infections then this 389 bp amplicon is a worthy candidate. A recent publication using the HVR of the HCV genome to identify recent infections (in this case < 1 year since infection) impressively reported accuracies > 95% 20 . These results suggest that using a combination of metrics, including the physical chemical features of a nucleotide sequence, may enhance both sensitivity and specificity for incidence estimations.…”

Polyvalent immunization elicits a synergistic broadly neutralizing immune response to hypervariable region 1 variants of hepatitis C virus

“…All the HVR1 nucleotide sequences covering the hypervariable region (81bp) were obtained from the Virus Pathogen Database and Analysis Resource (ViPR) ( 47 ). In addition, the following sequences were added from previous studies: 119 sequences obtained from patients with recent HCV infection, 256 sequences from chronic HCV infection, and 262 sequences from our previously published cross-reactivity experiment ( 20 , 48 ).…”

Community structure and temporal dynamics of SARS-CoV-2 epistatic network allow for early detection of emerging variants with altered phenotypes

“…Understanding the predictability of evolution and the relative impact of random and deterministic factors in evolutionary processes is a fundamental problem in life sciences. This problem gains an applied significance in the context of viruses and other pathogens, as even a modest degree of predictability of pathogen evolution can enhance our ability to forecast and, therein, control the spread of infectious diseases [1][2][3][4].…”