Discovery of a Novel Human Pegivirus in Blood Associated with Hepatitis C Virus Co-Infection

PLoS Pathogens

Samia N. Naccache¹  Marilee Marcinkus¹  John Hackett Jr.¹  Kenn Forberg¹  Michael G. Berg¹  Donald M. Jensen¹  Matthew Frankel¹  Andrew Aronsohn¹  Charles Y. Chiu²  Kevin Cheng²  Deanna Lee³  George Dawson³  Kelly Coller⁴  Catherine Brennan⁴ 

[1] Abbott Laboratories, Abbott Park, Illinois, United States of America;Center for Liver Diseases, University of Chicago Medical Center, Chicago, Illinois, United States of America;Department of Laboratory Medicine, University of California, San Francisco, California, United States of America;UCSF-Abbott Viral Diagnostics and Discovery Center, San Francisco, California, United States of America

关键词: Sequence alignment;    Hepatitis C virus;    HIV;    Multiple alignment calculation;    Next-generation sequencing;    Sequence assembly tools;    Phylogenetic analysis;    Serology;   

DOI  :  10.1371/journal.ppat.1005325

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

Hepatitis C virus (HCV) and human pegivirus (HPgV), formerly GBV-C, are the only known human viruses in the Hepacivirus and Pegivirus genera, respectively, of the family Flaviviridae. We present the discovery of a second pegivirus, provisionally designated human pegivirus 2 (HPgV-2), by next-generation sequencing of plasma from an HCV-infected patient with multiple bloodborne exposures who died from sepsis of unknown etiology. HPgV-2 is highly divergent, situated on a deep phylogenetic branch in a clade that includes rodent and bat pegiviruses, with which it shares <32% amino acid identity. Molecular and serological tools were developed and validated for high-throughput screening of plasma samples, and a panel of 3 independent serological markers strongly correlated antibody responses with viral RNA positivity (99.9% negative predictive value). Discovery of 11 additional RNA-positive samples from a total of 2440 screened (0.45%) revealed 93–94% nucleotide identity between HPgV-2 strains. All 12 HPgV-2 RNA-positive cases were identified in individuals also testing positive for HCV RNA (12 of 983; 1.22%), including 2 samples co-infected with HIV, but HPgV-2 RNA was not detected in non-HCV-infected individuals (p<0.0001), including those singly infected by HIV (p = 0.0075) or HBV (p = 0.0077), nor in volunteer blood donors (p = 0.0082). Nine of the 12 (75%) HPgV-2 RNA positive samples were reactive for antibodies to viral serologic markers, whereas only 28 of 2,429 (1.15%) HPgV-2 RNA negative samples were seropositive. Longitudinal sampling in two individuals revealed that active HPgV-2 infection can persist in blood for at least 7 weeks, despite the presence of virus-specific antibodies. One individual harboring both HPgV-2 and HCV RNA was found to be seronegative for both viruses, suggesting a high likelihood of simultaneous acquisition of HCV and HPgV-2 infection from an acute co-transmission event. Taken together, our results indicate that HPgV-2 is a novel bloodborne infectious virus of humans and likely transmitted via the parenteral route.

【 授权许可】

CC BY