Serum proteomics of hepatitis C virus infection reveals retinol-binding protein 4 as a novel regulator.
Persistent infection of hepatitis C virus (HCV) can lead to liver cirrhosis and hepatocellular carcinoma, which are currently diagnosed by invasive liver biopsy. Approximately 15-20 % of cases of chronic liver diseases in India are caused by HCV infection. In North India, genotype 3 is predominant, whereas genotype 1 is predominant in southern parts of India. The aim of this study was to identify differentially regulated serum proteins in HCV-infected Indian patients (genotypes 1 and 3) using a two-dimensional electrophoresis approach. We identified eight differentially expressed proteins by MS. Expression levels of one of the highly upregulated proteins, retinol-binding protein 4 (RBP4), was validated by ELISA and Western blotting in two independent cohorts. We also confirmed our observation in the JFH1 infectious cell culture system. Interestingly, the HCV core protein enhanced RBP4 levels and partial knockdown of RBP4 had a positive impact on HCV replication, suggesting a possible role for this cellular protein in regulating HCV infection. Analysis of RBP4-interacting partners using a bioinformatic approach revealed novel insights into the possible involvement of RBP4 in HCV-induced pathogenesis. Taken together, this study provided information on the proteome profile of the HCV-infected Indian population, and revealed a link between HCV infection, RBP4 and insulin resistance.
Department of Microbiology and Cell Biology, Indian Institute of Science, Bangalore 560 012, India.
K
K
Gouthamchandra
Department of Microbiology and Cell Biology, Indian Institute of Science, Bangalore 560 012, India.
Anuj
A
Kumar
Department of Microbiology and Cell Biology, Indian Institute of Science, Bangalore 560 012, India.
Shivaprasad
S
Shwetha
ICMR Virus Unit, Kolkata, ID & BG Hospital Campus, GB-4 (East Wing) 1st Floor, 57, Dr Suresh Chandra Banerjee Road, Beliaghata, Kolkata 700010, India.
Anirban
A
Mukherjee
Bioviz Technologies Pvt Ltd, Sagar Society, Road No. 2, Banjara Hills, Hyderabad 500 034, India.
Madhavi
M
Chandra
Yashoda Hospital, Secunderabad 500 044, India.
B
B
Ravishankar
Bioviz Technologies Pvt Ltd, Sagar Society, Road No. 2, Banjara Hills, Hyderabad 500 034, India.
M N
MN
Khaja
ICMR Virus Unit, Kolkata, ID & BG Hospital Campus, GB-4 (East Wing) 1st Floor, 57, Dr Suresh Chandra Banerjee Road, Beliaghata, Kolkata 700010, India.
Provash Chandra
PC
Sadhukhan
Department of Microbiology and Cell Biology, Indian Institute of Science, Bangalore 560 012, India.
Saumitra
S
Das
D000328:Adult; D000368:Aged; D015153:Blotting, Western; D015180:Electrophoresis, Gel, Two-Dimensional; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D019698:Hepatitis C, Chronic / Q000276:immunology*; D006801:Humans; D007194:India; D008297:Male; D013058:Mass Spectrometry; D008875:Middle Aged; D020543:Proteome / Q000032:analysis*; D054839:Retinol-Binding Proteins, Plasma / Q000032:analysis*; D044967:Serum / Q000737:chemistry*
D020543:Proteome; C101326:RBP4 protein, human; D054839:Retinol-Binding Proteins, Plasma