title: Detection of hepatitis C virus transmission by use of DNA mass spectrometry.
abstract: The molecular detection of transmission of rapidly mutating pathogens such as hepatitis C virus (HCV) is commonly achieved by assessing the genetic relatedness of strains among infected patients. We describe the development of a novel mass spectrometry (MS)-based approach to identify HCV transmission. MS was used to detect products of base-specific cleavage of RNA molecules obtained from HCV polymerase chain reaction fragments. The MS-peak profiles were found to reflect variation in the HCV genomic sequence and the intrahost composition of the HCV population. Serum specimens originating from 60 case patients from 14 epidemiologically confirmed outbreaks and 25 unrelated controls were tested. Neighbor-joining trees constructed using MS-peak profile-based Hamming distances showed 100% accuracy, and linkage networks constructed using a threshold established from the Hamming distances between epidemiologically unrelated cases showed 100% sensitivity and 99.93% specificity in transmission detection. This MS-based approach is rapid, robust, reproducible, cost-effective, and applicable to investigating transmissions of other pathogens.
authors.affiliation: Molecular Epidemiology and Bioinformatics Laboratory, Division of Viral Hepatitis, Centers for Disease Control and Prevention, Atlanta, Georgia 30329, USA. lkg7@cdc.gov
authors.forename: Lilia M
authors.initials: LM
authors.lastname: Ganova-Raeva
authors.forename: Zoya E
authors.initials: ZE
authors.lastname: Dimitrova
authors.forename: David S
authors.initials: DS
authors.lastname: Campo
authors.forename: Yulin
authors.initials: Y
authors.lastname: Lin
authors.forename: Sumathi
authors.initials: S
authors.lastname: Ramachandran
authors.forename: Guo-Liang
authors.initials: GL
authors.lastname: Xia
authors.forename: Christiane
authors.initials: C
authors.lastname: Honisch
authors.forename: Charles R
authors.initials: CR
authors.lastname: Cantor
authors.forename: Yury E
authors.initials: YE
authors.lastname: Khudyakov
mesh_terms: D000704:Analysis of Variance; D004279:DNA, Viral / Q000097:blood / Q000302:isolation & purification*; D016174:Hepacivirus / Q000235:genetics / Q000302:isolation & purification*; D006526:Hepatitis C / Q000097:blood / Q000453:epidemiology* / Q000635:transmission*; D006801:Humans; D013058:Mass Spectrometry / Q000379:methods*; D017720:Molecular Epidemiology; D010802:Phylogeny; D016133:Polymerase Chain Reaction; D012367:RNA, Viral / Q000097:blood; D012680:Sensitivity and Specificity; D014481:United States / Q000453:epidemiology
chemical_list: D004279:DNA, Viral; D012367:RNA, Viral