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A laboratory-adapted HCV JFH-1 strain is sensitive to neutralization and can gradually escape under the selection pressure of neutralizing human plasma.

Publication ,  Journal Article
Song, H; Ren, F; Li, J; Shi, S; Yan, L; Gao, F; Li, K; Zhuang, H
Published in: Virus Res
October 2012

Viral replication and neutralization of hepatitis C viruses (HCV) have been studied using the infectious molecular clone JFH-1. By passaging JFH-1 in hepatoma cells in the absence or presence of HCV neutralizing antibodies (nAbs), we investigated the molecular mechanisms of cell-culture adaptation and sensitivity to nAbs. The cell culture-adapted JFH-1 virus (JFH-1-CA) became more sensitive to nAbs than its parental virus. Sequence analysis revealed that the predominant viruses in the JFH-1-CA population carried two mutations in their envelopes (I414T and V293A). Plasma that could neutralize JFH-1-CA was found in 2 of 7 HCV-infected individuals who have cleared the virus in blood. Plasma 226233 with a higher 50% neutralization titer was used for in vitro selection of neutralization resistant viruses. Under the increasing selection pressure of plasma 226233, the neutralizing sensitivity of JFH-1-CA decreased gradually. Two mutations (T414I and P500S) in envelope were found in all but one sequenced clones in the viral population after eight rounds of selection. Interestingly, the cell-culture adapted mutation I414T reverted back to the wild-type residue (I414) under the selection pressure. By introducing mutations at positions 414 and 500 into the JFH-1 clone, we confirmed that the T414I mutation alone can confer neutralization resistance. The results of this current study suggest that nAbs are present in a subset of HCV-infected individuals who have cleared the virus in blood. Our data also provide the first evidence that, the E2 residue P500, located within a previously identified highly conserved polyclonal epitope, may be a target for neutralizing antibodies present in individual who have spontaneously resolved the HCV infection.

Duke Scholars

Published In

Virus Res

DOI

EISSN

1872-7492

Publication Date

October 2012

Volume

169

Issue

1

Start / End Page

154 / 161

Location

Netherlands

Related Subject Headings

  • Young Adult
  • Virus Cultivation
  • Virology
  • Viral Envelope Proteins
  • Mutation, Missense
  • Male
  • Immune Evasion
  • Humans
  • Hepatocytes
  • Hepatitis C Antibodies
 

Citation

APA
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ICMJE
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Song, H., Ren, F., Li, J., Shi, S., Yan, L., Gao, F., … Zhuang, H. (2012). A laboratory-adapted HCV JFH-1 strain is sensitive to neutralization and can gradually escape under the selection pressure of neutralizing human plasma. Virus Res, 169(1), 154–161. https://doi.org/10.1016/j.virusres.2012.07.022
Song, Hongshuo, Furong Ren, Jin Li, Shuang Shi, Ling Yan, Feng Gao, Kui Li, and Hui Zhuang. “A laboratory-adapted HCV JFH-1 strain is sensitive to neutralization and can gradually escape under the selection pressure of neutralizing human plasma.Virus Res 169, no. 1 (October 2012): 154–61. https://doi.org/10.1016/j.virusres.2012.07.022.
Song, Hongshuo, et al. “A laboratory-adapted HCV JFH-1 strain is sensitive to neutralization and can gradually escape under the selection pressure of neutralizing human plasma.Virus Res, vol. 169, no. 1, Oct. 2012, pp. 154–61. Pubmed, doi:10.1016/j.virusres.2012.07.022.
Journal cover image

Published In

Virus Res

DOI

EISSN

1872-7492

Publication Date

October 2012

Volume

169

Issue

1

Start / End Page

154 / 161

Location

Netherlands

Related Subject Headings

  • Young Adult
  • Virus Cultivation
  • Virology
  • Viral Envelope Proteins
  • Mutation, Missense
  • Male
  • Immune Evasion
  • Humans
  • Hepatocytes
  • Hepatitis C Antibodies