Evidence map›Paper›PMID 22674987›Full record

ArticleJournal of virology2012

Cell culture-adaptive mutations promote viral protein-protein interactions and morphogenesis of infectious hepatitis C virus.

Jieyun Jiang, Guangxiang Luo

Open access · bronzeAbstract read
In one paragraph

Article in Journal of virology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.

0numbers the graph read from it
0cells of the map it votes in
41citing papers in PubMed
4.0field-weighted citation impact, top 6% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

41 citing papers in PubMed, 55 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

2 authors at 2 institutions in 2 countries.

Jieyun JiangDepartment of Microbiology, Immunology and Molecular Genetics, University of Kentucky College of Medicine, Lexington, Kentucky, USA.
Guangxiang Luo
Peking University · CNUniversity of Kentucky · US

Funding

Underlying Mechanisms of ApoE in HCV Infection and AssemblyR01AI097318 · NIAID · UNIVERSITY OF KENTUCKY · PI LUO, GUANGXIANG GEORGE · 2012 to 2016
$1.8M
Viral and Cellular Determinants of HCV AssemblyR01AI091953 · NIAID · UNIVERSITY OF KENTUCKY · PI LUO, GUANGXIANG GEORGE · 2011 to 2014
$1.5M
Transgenic mouse models of HCV infection and replicationR21AI092074 · NIAID · UNIVERSITY OF KENTUCKY · PI JIANG, JIEYUN · 2011 to 2012
$408k
NIAID NIH HHS AI091953NIAID NIH HHS AI092074NIAID NIH HHS AI097318NIAID NIH HHS R01 AI091953NIAID NIH HHS R01 AI097318NIAID NIH HHS R21 AI092074
6 · The paper itself

Abstract

Recent genetic studies suggested that viral nonstructural (NS) proteins play important roles in morphogenesis of flaviviruses, particularly hepatitis C virus (HCV). Adaptive and compensatory mutations occurring in different NS proteins were demonstrated to promote HCV production in cell culture. However, the underlying molecular mechanism of NS proteins in HCV morphogenesis is poorly understood. We have isolated a cell culture-adapted HCV of genotype 2a (JFH1) which grew to an infectious titer 3 orders of magnitude higher than that of wild-type virus. Sequence analysis identified a total of 16 amino acid mutations in core (C), E1, NS2, NS3, NS5A, and NS5B, with the majority of mutations clustered in NS5A. Reverse genetic analysis of these mutations individually or in different combinations demonstrated that amino acid mutations in NS2 and NS5A markedly enhanced HCV production. Additionally, mutations in C, E1, NS3, and NS5B synergistically promoted HCV production in the background of NS2 and NS5A mutations. Adaptive mutations in NS5A domains I, II, and III independently enhanced HCV production, suggesting that all three domains of NS5A are important for HCV morphogenesis. More importantly, adaptive mutations greatly enhanced physical interactions among HCV structural and NS proteins, as determined by studies with coimmunoprecipitation and mammalian two-hybrid assays. Collectively, these findings demonstrate that adaptive mutations can enhance specific protein-protein interactions among viral structural and NS proteins and therefore promote the assembly of infectious HCV particles.

Indexed as

MutationAdaptation, PhysiologicalCell Culture TechniquesCell LineHepacivirusHepatitis CHumansProtein BindingProtein Structure, TertiaryViral Nonstructural ProteinsViral Structural ProteinsVirus CultivationViral Nonstructural ProteinsViral Structural Proteins

Identifiers

PMID22674987
PMCPMC3416171
OpenAlexW2023402045

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.