期刊
VIROLOGY
卷 448, 期 -, 页码 117-124出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.virol.2013.10.003
关键词
Viroporin; Ion channel gating; Natural virus variants; Particle acid stability; Drug resistance
类别
资金
- BBSRC CASE Ph.D. Scholarship
- Pfizer
- University of Leeds Biomedical Health Research Centre (BHRC)
- Medical Research Council New Investigator Research Grant [G0700124]
- Wellcome Trust Investigator Award
- University of Leeds BHRC
- NIH [1 R01 AI 66209-01]
- MRC [G0700124] Funding Source: UKRI
- Medical Research Council [G0700124] Funding Source: researchfish
Secreted infectious particles generated by the genotype 2a JFH-1 hepatitis C virus infectious clone are resistant to acidic pH, whereas intracellular virions remain acid-labile. Thus, JFH-1 particles are thought to undergo pH maturation as they are secreted from the cell. Here, we demonstrate that both infectious intracellular and secreted genotype 1 a (H77)/JFH-1 chimaeric particles display enhanced acid sensitivity compared with JFH-1, although pH maturation still occurs upon release. Introduction of p7 sequences from genotype la infected HCV patients into the H77/JFH-1 background yielded variable effects on infectious particle production and sensitivity to small molecule inhibitors. However, two selected patient p7 sequences increased the acid stability of secreted, but not intracellular H77/JFH-1 particles, suggesting that p7 directly influences particle pH maturation via an as yet undefined mechanism. We propose that HCV particles vary in acid stability, and that this may be dictated by variations in both canonical structural proteins and p7. (C) 2013 Elsevier Inc. All rights reserved.
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