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HCV genetic diversity can be used to infer infection recency and time since Iifection


Abstract

HIV-1 genetic diversity can be used to infer time since infection (TSI) and infection recency. We adapted this approach for HCV and identified genomic regions with informative diversity. We included 72 HCV/HIV-1 coinfected participants of the Swiss HIV Cohort Study, for whom reliable estimates of infection date and viral sequences were available. Average pairwise diversity (APD) was calculated over each codon position for the entire open reading frame of HCV. Utilizing cross validation, we evaluated the correlation of APD with TSI, and its ability to infer TSI via a linear model. We additionally studied the ability of diversity to classify infections as recent (infected for <1 year) or chronic, using receiver-operator-characteristic area under the curve (ROC-AUC) in 50 patients whose infection could be unambiguously classified as either recent or chronic. Measuring HCV diversity over third or all codon positions gave similar performances, and notable improvement over first or second codon positions. APD calculated over the entire genome enabled classification of infection recency (ROC-AUC = 0.76). Additionally, APD correlated with TSI (R$^{2}$ = 0.33) and could predict TSI (mean absolute error = 1.67 years). Restricting the region over which APD was calculated to E2-NS2 further improved accuracy (ROC-AUC = 0.85, R$^{2}$ = 0.54, mean absolute error = 1.38 years). Genetic diversity in HCV correlates with TSI and is a proxy for infection recency and TSI, even several years post-infection.

Abstract

HIV-1 genetic diversity can be used to infer time since infection (TSI) and infection recency. We adapted this approach for HCV and identified genomic regions with informative diversity. We included 72 HCV/HIV-1 coinfected participants of the Swiss HIV Cohort Study, for whom reliable estimates of infection date and viral sequences were available. Average pairwise diversity (APD) was calculated over each codon position for the entire open reading frame of HCV. Utilizing cross validation, we evaluated the correlation of APD with TSI, and its ability to infer TSI via a linear model. We additionally studied the ability of diversity to classify infections as recent (infected for <1 year) or chronic, using receiver-operator-characteristic area under the curve (ROC-AUC) in 50 patients whose infection could be unambiguously classified as either recent or chronic. Measuring HCV diversity over third or all codon positions gave similar performances, and notable improvement over first or second codon positions. APD calculated over the entire genome enabled classification of infection recency (ROC-AUC = 0.76). Additionally, APD correlated with TSI (R$^{2}$ = 0.33) and could predict TSI (mean absolute error = 1.67 years). Restricting the region over which APD was calculated to E2-NS2 further improved accuracy (ROC-AUC = 0.85, R$^{2}$ = 0.54, mean absolute error = 1.38 years). Genetic diversity in HCV correlates with TSI and is a proxy for infection recency and TSI, even several years post-infection.

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Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > Institute of Medical Virology
04 Faculty of Medicine > Epidemiology, Biostatistics and Prevention Institute (EBPI)
04 Faculty of Medicine > University Hospital Zurich > Clinic for Infectious Diseases
Dewey Decimal Classification:610 Medicine & health
Scopus Subject Areas:Health Sciences > Infectious Diseases
Life Sciences > Virology
Language:English
Date:31 October 2020
Deposited On:09 Dec 2020 15:25
Last Modified:01 Jan 2021 21:03
Publisher:MDPI Publishing
ISSN:1999-4915
OA Status:Gold
Free access at:PubMed ID. An embargo period may apply.
Publisher DOI:https://doi.org/10.3390/v12111241
PubMed ID:33142675

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