Characterization of pseudotype VSV possessing HCV envelope proteins

被引:130
作者
Matsuura, Y
Tani, H
Suzuki, K
Kimura-Someya, T
Suzuki, R
Aizaki, H
Ishii, K
Moriishi, K
Robison, CS
Whitt, MA
Miyamura, T
机构
[1] Osaka Univ, Res Inst Microbial Dis, Res Ctr Emerging Infect Dis, Suita, Osaka 5650871, Japan
[2] Natl Inst Infect Dis, Dept Virol 2, Tokyo, Japan
[3] Japan Tobacco Inc, Pharmaceut Frontier Res Labs, Yokohama, Kanagawa 227, Japan
[4] Univ Tennessee, Dept Microbiol & Immunol, Memphis, TN USA
关键词
hepatitis C virus; envelope proteins; pseudotype virus; infection;
D O I
10.1006/viro.2001.0971
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
The genome of hepatitis C virus (HCV) encodes two envelope glycoproteins (E1 and E2), which are thought to be responsible for receptor binding and membrane fusion resulting in virus penetration. To investigate cell surface determinants important for HCV infection, we used a recombinant vesicular stomatitis virus (VSV) in which the glycoprotein gene was replaced with a reporter gene encoding green fluorescent protein (GFP) and produced HCV-VSV pseudotypes possessing chimeric HCV E1 or E2 glycoproteins, either individually or together. The infectivity of the pseudotypes was determined by quantifying the number of cells expressing the GFP reporter gene. Pseudotypes that contained both of the chimeric E1 and E2 proteins exhibited 10-20 times higher infectivity on HepG2 cells than the viruses possessing either of the glycoproteins individually. These results indicated that both E1 and E2 envelope proteins are required for maximal infection by HCV. The infectivity of the pseudotype virus was not neutralized by anti-VSV polyclonal antibodies, Bovine lactoferrin specifically inhibited the infection of the pseudotype virus. Treatment of HepG2 cells with Pronase, heparinase, and heparitinase but not with phospholipase C and sodium periodate reduced the infectivity. Therefore, cell surface proteins and some glycosaminoglycans play an important role in binding or entry of HCV into susceptible cells, The pseudotype VSV possessing the chimeric HCV glycoproteins might offer an efficient tool for future research on cellular receptors for HCV and for the development of prophylactics and therapeutics for hepatitis C. (C) 2001 Academic Press.
引用
收藏
页码:263 / 275
页数:13
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