Toray Industries, Inc.

Tokyo Metropolitan Institute of Medical Science

National Institute of Infectious Diseases

Tokyo Metropolitan Organization for Medical Research

Other

The General Hospital Corporation

Chinese Academy of Sciences

Institut National De La Sante Et De La Recherche Medicale

The University of Tokyo

Nihon University

Public University Corporation Nagoya City University

Ralf Bartenschlager

Bartenschlager, Ralf

Takaji Wakita

Tomoko Date

Takanobu Kato

Saburo Sone

Jun-ichi Tanabe

Michiko Miyamoto

Jack Raymond Wands

Jun-Ichi Tanabe

Tetsuro Suzuki

Koji Ishii

Catherine Julia Pachuk

Tatsuo Miyamura

Izumu Saito

Michinori Kohara

Vincent R Zurawski, Jr

Noriko Nakamura

Hiromichi Yonekawa

Choji Taya

Leslie R Coney

Daisuke Akazawa

Ryosuke Suzuki

Hitoshi Takahashi

Yoshihiro Kitamura

Yasuhito Tanaka

Masashi Mizokami

Kazumi Nishimura

Katsutoshi Tokushige

Hiroshi Yokokawa

Mohsan Saeed

Patrick Maurel

Yuko Akazawa

Lijuan Yu

Chie Aoki

Yoko Shimizu

Asako Murayama

Claire Gondeau

Jun-Ichi c/o Basic Research Laboratories Tanabe

Takanobu Eminence-Ishikawabashi 206 Kato

Tomoko; Date

Michiko; Miyamoto

Saburo; Sone

A nucleic acid includes, in the following order, a 5' untranslated region comprising a particular nucleotide sequence of the genome of hepatitis C virus genotype 3a; a nucleotide sequence encoding a particular amino acid sequence of an NS3 protein, a nucleotide sequence encoding a particular amino acid sequence of an NS4A protein, a nucleotide sequence encoding a particular amino acid sequence of an NS4B protein, a nucleotide sequence encoding a particular amino acid sequence of an NS5A protein, a nucleotide sequence encoding a particular amino acid sequence of an NS5B protein of the hepatitis C virus genotype 3a; and a 3&#x2032; untranslated region comprising a particular nucleotide sequence of a genome of hepatitis C virus genotype 3a.

Nucleic acid construct comprising nucleic acid derived from genome of hepatitis C virus of genotype 3a

A subgenomic replicon RNA (nucleic acid) having an excellent autonomously replicating ability and a fullgenomic replicon RNA (nucleic acid) having an excellent autonomously replicating ability and infectious HCV particle-producing ability, each derived from a novel HCV of genotype 1b, are provided. Particularly, a subgenomic replicon RNA (nucleic acid) and a fullgenomic replicon RNA (nucleic acid), each derived from an HCV genome of the NC1 strain which is a novel HCV genotype 1b isolated from a patient with acute severe hepatitis C, are provided.

Nucleic acid construct comprising nucleic acid derived from genome of hepatitis C virus of genotype 1B, hepatitis C virus genome-replicating cells transfected with the same, and method for producing infectious hepatitis C virus particles

A nucleic acid includes the 5' untranslated region, a virus protein-coding region including the NS3 protein coding sequence, the NS4A protein coding sequence, the NS4B protein coding sequence, the NS5A protein coding sequence, and the NS5B protein coding sequence, and the 3&#x2032; untranslated region of the HCV J6CF genome in that order from the 5&#x2032; to 3&#x2032; direction. The NS4A protein coding sequence has a mutation for substituting alanine at position 1680 with glutamic acid, as determined on the basis of the amino acid sequence of the precursor protein of the J6CF strain.

Mutant replicon derived from genome of hepatitis C virus J6CF strain

The present invention provides modified hepatitis C virus genomic RNA, comprising nucleotide sequences of genomic RNA portions of two or more types of hepatitis C viruses, which comprises a 5' untranslated region, a core protein coding sequence, an E1 protein coding sequence, a p7 protein coding sequence, an E2 protein coding sequence, an NS2 protein coding sequence, an NS3 protein coding sequence, an NS4A protein coding sequence, an NS4B protein coding sequence, an NS5A protein coding sequence, an NS5B protein coding sequence, and a 3&#x2032; untranslated region, and which can be autonomously replicated. In particular, the present invention relates to modified hepatitis C virus genomic RNA, which can be autonomously replicated by substitution of the RNA sequence portion encoding NS3, NS4, NS5A, and NS5B proteins of hepatitis C virus genomic RNA with a partial RNA sequence encoding NS3, NS4, NS5A, and NS5B proteins of a JFH1 strain shown in SEQ ID NO: 1.

Modified human hepatitis C virus genomic RNA that can be autonomously replicated

An objective of this invention is to provide an HCV strain with a high capacity for virus production in a cell culture system. This invention provides a nucleic acid encoding a polyprotein precursor of the hepatitis C virus JFH1 strain having one or more amino acid substitutions, wherein the polyprotein precursor comprises at least substitution of glutamine at position 862 with arginine, as determined with reference to the amino acid sequence as shown in SEQ ID NO: 2 in the Sequence Listing.

Infectious hepatitis C virus&#x2014;high producing HCV variants and use thereof

The present invention provides an antibody that specifically binds to envelope protein 2 of HCV of genotype 2but does not immunologically react with envelope protein 2 of HCV of genotype 1.

Antibody binding to envelope protein 2 of hepatitis C virus and method for identifying genotype of hepatitis C virus using the same

The present invention provides a nucleic acid comprises a 5' untranslated region, an NS3 protein coding region, an NS4A protein coding region, an NS4B protein coding region, an NS5A protein coding region, an NS5B protein coding region, and a 3&#x2032; untranslated region of a hepatitis C virus genome, wherein the nucleic acid has nucleotide substitutions causing one or more amino acid substitutions selected from the group consisting of M(1205)K, F(1548)L, C(1615)W, T(1652)N, A(2196)T, A(2218)S, H(2223)Q, Q(2281)R, K(2520)N, and G(2374)S, as defined using the amino acid sequence shown in SEQ ID NO: 6 in the Sequence Listing as a reference sequence, in the NS3 protein coding region, the NS5A protein coding region, or the NS5B protein coding region.

Nucleic acid derived from hepatitis C virus and expression vector, transformed cell, and hepatitis C virus particles each prepared by using the same

The present invention relates to a replicon RNA comprising a nucleotide sequence at least containing the 5' untranslated region, the nucleotide sequence encoding NS3 protein, NS4A protein, NS4B protein, NS5A protein and NS5B protein, and the 3&#x2032; untranslated region on the genomic RNA of hepatitis C virus of genotype 2a.

Nucleic acid construct containing a nucleic acid derived from the genome of hepatitis C virus (HCV) of genotype 2a, and a cell having such nucleic acid construct introduced therein

This invention provides infectious chimeric HCV particles that can be used for vaccines. This invention further provides a nucleic acid comprising a chimeric gene derived from the hepatitis C virus comprising regions each encoding Core protein, E1 protein, E2 protein and p7 protein derived from a hepatitis C virus strain other than JFH-1 strain; NS2 protein derived from JFH-1 strain or a hepatitis C virus strain other than JFH-1 strain, or a chimeric NS2 protein of NS2 protein derived from JFH-1 strain and NS2 protein derived from a hepatitis C virus strain other than JFH-1 strain; and NS3 protein, NS4A protein, NS4B protein, NS5A protein, and NS5B protein derived from JFH-1 strain in that order in 5' to 3&#x2032; direction, wherein the 328th proline residue from the amino acid residue at N-terminus of the Core protein is substituted with an amino acid residue other than proline. This invention further provides chimeric HCV particles comprising such nucleic acid, and use of such HCV particles for vaccines.

Nucleic acid comprising chimeric gene derived from hepatitis C virus

An object of the present invention is to provide an antibody inhibiting infection with hepatitis C virus (HCV). The present invention provides an anti-hepatitis C virus antibody that recognizes a whole or a part of the conformation of a hepatitis C virus particle as an epitope and binds thereto, so as to be able to inhibit the binding of hepatitis C virus to the surface of a host cell and to inhibit HCV infection, a humanized antibody thereof, and an inhibitory agent for infection with hepatitis C virus.

Antibody having activity of inhibiting hepatitis C virus (HCV) infection and use thereof

The present invention provides a method for replicating efficiently an RNA containing fulllength HCV genomic sequence and a method for producing HCV virus particles containing fulllength HCV replicon RNA or fulllength HCV genomic RNA by using a cell culture system. Further, the present invention relates to a method for producing hepatitis C virus particles which comprises culturing a cell, into which a replicon RNA comprising a nucleotide sequence comprising a fulllength genomic RNA sequence of hepatitis C virus of the genotype 2a, at least one selectable marker gene and/or at least one reporter gene and at least one IRES sequence or the fulllength genomic RNA of hepatitis C virus of the genotype 2a is introduced, and generating virus particles in the culture medium. Still further the present invention relates also to a hepatitis C vaccine and an antibody against hepatitis C virus particles.

Nucleic acid construct containing full length genome of human hepatitis C virus, recombinant full length virus genome-replicating cells having the nucleic acid construct transferred thereinto and method of producing hepatitis C virus particle

The present invention relates to a method for producing a recombinant hepatitis C virus-like particle comprising the steps of introducing into (i) a cell in which an RNA replicon comprising a nucleotide sequence comprising the 5' untranslated region, the nucleotide sequence coding for the NS3, NS4A, NS4B, NS5A, and NS5B proteins, and the 3&#x2032; untranslated region of a genome RNA derived from a hepatitis C virus strain autonomously replicates, (ii) a vector expressing the Core, E1, E2, and p7 proteins derived from a hepatitis C virus strain that is the same as or different from that as defined in the above (i), culturing the cell, and recovering the produced virus-like particle, and a recombinant hepatitis C virus particle produced by this method.

Recombinant human hepatitis C virus-like particle and method for producing the same

The present invention relates to a method for producing infectious hepatitis C virus (HCV) particles, comprising a step of introducing an expression vector into a cell that allows HCV proliferation, such expression vector comprising: DNA sequences encoding the 5' untranslated region, structural proteins, and, if necessary, non-structural proteins of HCV and DNA sequences encoding non-structural proteins and the 3&#x2032; untranslated region derived from the HCV JFH1 strain, which are located downstream of a polymerase I promoter; and a DNA fragment containing an RNA polymerase I terminator, which is located further downstream thereof.

High production system for infectious hepatitis C virus particle

Growing community of inventors

Tokyo, Japan

Takaji Wakita