Discovery of a Novel Human Pegivirus in Blood Associated with Hepatitis C Virus Co-Infection.
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-generat...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2015-12-01
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| Series: | PLoS Pathogens |
| Online Access: | http://europepmc.org/articles/PMC4676677?pdf=render |
| _version_ | 1818022750936104960 |
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| author | Michael G Berg Deanna Lee Kelly Coller Matthew Frankel Andrew Aronsohn Kevin Cheng Kenn Forberg Marilee Marcinkus Samia N Naccache George Dawson Catherine Brennan Donald M Jensen John Hackett Charles Y Chiu |
| author_facet | Michael G Berg Deanna Lee Kelly Coller Matthew Frankel Andrew Aronsohn Kevin Cheng Kenn Forberg Marilee Marcinkus Samia N Naccache George Dawson Catherine Brennan Donald M Jensen John Hackett Charles Y Chiu |
| author_sort | Michael G Berg |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-10T03:33:24Z |
| format | Article |
| id | doaj.art-0dacb4cffa374967a379dcb0c931de57 |
| institution | Directory Open Access Journal |
| issn | 1553-7366 1553-7374 |
| language | English |
| last_indexed | 2024-12-10T03:33:24Z |
| publishDate | 2015-12-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Pathogens |
| spelling | doaj.art-0dacb4cffa374967a379dcb0c931de572022-12-22T02:03:45ZengPublic Library of Science (PLoS)PLoS Pathogens1553-73661553-73742015-12-011112e100532510.1371/journal.ppat.1005325Discovery of a Novel Human Pegivirus in Blood Associated with Hepatitis C Virus Co-Infection.Michael G BergDeanna LeeKelly CollerMatthew FrankelAndrew AronsohnKevin ChengKenn ForbergMarilee MarcinkusSamia N NaccacheGeorge DawsonCatherine BrennanDonald M JensenJohn HackettCharles Y ChiuHepatitis 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.http://europepmc.org/articles/PMC4676677?pdf=render |
| spellingShingle | Michael G Berg Deanna Lee Kelly Coller Matthew Frankel Andrew Aronsohn Kevin Cheng Kenn Forberg Marilee Marcinkus Samia N Naccache George Dawson Catherine Brennan Donald M Jensen John Hackett Charles Y Chiu Discovery of a Novel Human Pegivirus in Blood Associated with Hepatitis C Virus Co-Infection. PLoS Pathogens |
| title | Discovery of a Novel Human Pegivirus in Blood Associated with Hepatitis C Virus Co-Infection. |
| title_full | Discovery of a Novel Human Pegivirus in Blood Associated with Hepatitis C Virus Co-Infection. |
| title_fullStr | Discovery of a Novel Human Pegivirus in Blood Associated with Hepatitis C Virus Co-Infection. |
| title_full_unstemmed | Discovery of a Novel Human Pegivirus in Blood Associated with Hepatitis C Virus Co-Infection. |
| title_short | Discovery of a Novel Human Pegivirus in Blood Associated with Hepatitis C Virus Co-Infection. |
| title_sort | discovery of a novel human pegivirus in blood associated with hepatitis c virus co infection |
| url | http://europepmc.org/articles/PMC4676677?pdf=render |
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