5 New Hepatitis C Abstracts

[Guest guest]

J Infect Dis. 2011 Oct;204(8):1186-90.

Vaccine-induced cross-genotype reactive neutralizing antibodies against

hepatitis C virus.

Meunier JC, Gottwein JM, Houghton M, RS, Emerson SU, Bukh J, Purcell RH.

Source

Laboratory of Infectious Diseases, National Institute of Allergy and Infectious

Diseases, National Institutes of Health, Bethesda, land.

Abstract

We detected cross-reactive neutralizing antibodies (NtAb) against hepatitis C

virus (HCV) in chimpanzees vaccinated with HCV-1 (genotype 1a) recombinant E1/E2

envelope glycoproteins. Five vaccinated chimpanzees, protected following HCV-1

challenge, were initially studied using the heterologous H77 (genotype 1a) HCVpp

assay. All animals had developed NtAb after the second vaccination; 4 animals

had reciprocal titers of ≥200 at the time of challenge. Using genotypes 1a-6a

HCV pseudoparticles (HCVpp) and cell culture-derived HCV (HCVcc) assays,

cross-reactive NtAb were detected against 1a, 4a, 5a, and 6a, with limited

reactivity against 2a and 3a. Our study provides encouragement for the

development of a recombinant envelope-based vaccine against hepatitis C.

PMID: 21917891 [PubMed - in process]

Related citations

------------------------------------------

J Infect Dis. 2011 Oct;204(8):1181-5.

Altered Expression of SHIP, a Toll-like Receptor Pathway Inhibitor, Is

Associated With the Severity of Liver Fibrosis in Chronic Hepatitis C Virus

Infection.

Katsounas A, Trippler M, Kottilil S, Lempicki RA, Gerken G, Schlaak JF.

Source

Department of Gastroenterology and Hepatology, University Hospital of Essen,

Essen 45147, Germany.

Abstract

Hepatitis C-related fibrogenesis has been shown to involve complex interactions

between peripheral and hepatic immune responses. Peripheral whole blood (PB)

samples from patients with chronic hepatitis C (n = 36) were subjected to

microarray analysis in order to identify gene expression patterns associated

with immune pathways in PB and hepatic fibrosis. Distinct regulation of gene

expression of inositol polyphosphate-5-phosphatase/145kDa (INPP5D or SHIP), a

TLR2/TLR4-inhibitor, and heat shock protein 8/22kDa (HSPB8), an endogenous

TLR4-ligand, during fibrogenesis was identified and could be confirmed by

quantitative reverse-transcription polymerase chain reaction. These results

suggest a potential link between peripheral activity of the TLR4-pathway,

peripheral SHIP-dependent immune regulation, and liver fibrosis.

PMID: 21917890 [PubMed - in process]

Related citations

---------------------------------------------

J Infect Dis. 2011 Oct;204(8):1172-80.

Monoclonal Antibody 2-152a Suppresses Hepatitis C Virus Infection Through

Betaine/GABA Transporter-1.

Satoh M, Saito M, Takano T, Kasama Y, Nishimura T, Nishito Y, Hirata Y, Arai M,

Sudoh M, Kai C, Kohara M, Tsukiyama-Kohara K.

Source

Department of Experimental Phylaxiology, Faculty of Life Sciences, Kumamoto

University, Honjo Kumamoto City.

Abstract

Background. We recently established a monoclonal antibody (2-152a MAb) that

binds to 3β-hydroxysterol-Δ24-reductase (DHCR24) by immunizing mice with cells

(RzM6-LC) persistently expressing hepatitis C virus (HCV). Here, we aimed to

analyze the activity of 2-152a MAb against HCV replication and explore the

molecular mechanism underlying the antiviral activity. Methods. We

characterized the effects of 2-152a MAb on HCV replication and performed a

microarray analysis of antibody-treated HCV replicon cells. The molecules

showing a significant change after the antibody treatment were screened to

examine their relationship with HCV replication. Results. The antibody had

antiviral activity both in vitro and in vivo (chimeric mice). In the microarray

analysis, 2-152a MAb significantly suppressed the expression of betaine/GABA

transporter-1 (BGT-1) in 2 HCV replicon cell lines but not in HCV-cured cells.

Silencing of BGT-1 expression by small interfering RNA (siRNA) revealed

significant suppression of HCV replication and infection without cytotoxicity.

Further, BGT-1 expression was significantly increased in the presence of HCV (P

< .05). Conclusions. Our results suggest that 2-152a MAb suppresses HCV

replication and infection through BGT-1. These findings highlight important

roles of BGT-1 in HCV replication and reveal a possible target for anti-HCV

therapy.

PMID: 21917889 [PubMed - in process]

Related citations

----------------------------------------------------------

J Med Virol. 2011 Nov;83(11):1930-7. doi: 10.1002/jmv.22168.

Clinical evaluation of the signal-to-cutoff ratios of hepatitis C virus antibody

screening tests used in China.

Wu S, Liu Y, Cheng L, Yin B, Peng J, Sun Z.

Source

Department of Clinical Laboratory, Tongji Hospital of Tongji Medical College,

Huazhong University of Science and Technology, Wuhan, Hubei, China.

Abstract

The clinical diagnosis of hepatitis C virus (HCV) infection is important to

direct an accurate course of therapy. Previous studies have reported a

correlation between the signal-to-cutoff (S/CO) ratios of the anti-HCV screening

test and confirm HCV infections for American anti-HCV screening kits as well as

for those in China. It is currently unknown whether clinical laboratories use

the same threshold S/CO ratios under routine conditions and if these values are

acceptable for the analysis of Chinese samples. A total of 336 anti-HCV

screening-test-positive serum samples were tested in duplicate using different

lots of three most commonly used enzyme immunoassay (EIA) kits available in

China. Samples were also tested using the Architect Anti-HCV chemiluminescent

microparticle immunoassay (CMIA) kit and measured for HCV RNA. Recombinant

immunoblot assays (RIBA) were additionally performed on samples with HCV

RNA-negative results with RIBA HCV 3.0. The relationship between S/CO ratios and

confirmed HCV infection rates were analyzed. The threshold S/CO ratio for each

screening kit correlated with the ≥95% positive predictive value was InTec

12.0, KHB 4.0, Wantai 5.0, and Abbott Architect 5.0. Therefore, the same

threshold S/CO ratios for manufactured domestically EIA kits was difficult to

attain. A multi-center study with a large sample size is required to identify a

uniform threshold S/CO ratio for use in different diagnostic laboratories.

Alternatively, individual laboratories may be required to establish threshold

S/CO ratios in their own laboratories to obtain consistent diagnostic results.

J. Med. Virol. 83:1930-1937, 2011. © 2011 Wiley-Liss, Inc.

Copyright © 2011 Wiley-Liss, Inc.

PMID: 21915868 [PubMed - in process]

Related citations

-------------------------------------------------------------

J Med Virol. 2011 Nov;83(11):1924-9. doi: 10.1002/jmv.22216.

Prevalence of Amino acid mutation in hepatitis C virus core region among

Japanese volunteer blood donors.

Furui Y, Hoshi Y, Murata K, Ito K, Suzuki K, Uchida S, Satake M, Mizokami M,

Tadokoro K.

Source

Central Blood Institute, Japanese Red Cross, Tokyo, Japan.

Abstract

It is not known whether there is a trend of increasing or decreasing incidence

of new hepatitis C virus (HCV) infections in Japan. From the treatment point of

view, it is important to verify HCV genotypes and the prevalence of

treatment-resistant clones of HCV. At the Japanese Red Cross blood centers, all

blood samples obtained from blood donation have been screened using serological

methods and the minipool nucleic acid amplification testing. One hundred and

fourteen donors have been identified over the past 10 years to be HCV RNA-only

positive without detectable anti-HCV and were considered to be in the acute

phase of HCV infection. There was a trend of decreasing incidence of such new

infections among the blood donors. HCV RNA-only-positive samples were examined

further for genotyping and HCV RNA quantitation. Genotype 2 (2a plus 2b) was

predominant (78.2%) among them followed by genotype 1b (21.2%). Direct

sequencing was carried out to detect the possible treatment-resistant mutant

clones 70Q and 91M, clones with amino acid substitutions at positions 70 and 91

of the HCV core protein, respectively. 70Q and 91M were found regularly in

donors with genotype 1b, but not in those with other genotypes. No particular

endemic areas for the mutant clones were identified. There was no significant

difference in the mean viral titer between the 70Q mutant type and the non-70Q

wild-type. Even in newly infected people, the mutant clone 70Q was detected

frequently. J. Med. Virol. 83:1924-1929, 2011. © 2011 Wiley-Liss, Inc.

Copyright © 2011 Wiley-Liss, Inc.

PMID: 21915867 [PubMed - in process]

[Guest guest]

J Infect Dis. 2011 Oct;204(8):1186-90.

Vaccine-induced cross-genotype reactive neutralizing antibodies against

hepatitis C virus.

Meunier JC, Gottwein JM, Houghton M, RS, Emerson SU, Bukh J, Purcell RH.

Source

Laboratory of Infectious Diseases, National Institute of Allergy and Infectious

Diseases, National Institutes of Health, Bethesda, land.

Abstract

We detected cross-reactive neutralizing antibodies (NtAb) against hepatitis C

virus (HCV) in chimpanzees vaccinated with HCV-1 (genotype 1a) recombinant E1/E2

envelope glycoproteins. Five vaccinated chimpanzees, protected following HCV-1

challenge, were initially studied using the heterologous H77 (genotype 1a) HCVpp

assay. All animals had developed NtAb after the second vaccination; 4 animals

had reciprocal titers of ≥200 at the time of challenge. Using genotypes 1a-6a

HCV pseudoparticles (HCVpp) and cell culture-derived HCV (HCVcc) assays,

cross-reactive NtAb were detected against 1a, 4a, 5a, and 6a, with limited

reactivity against 2a and 3a. Our study provides encouragement for the

development of a recombinant envelope-based vaccine against hepatitis C.

PMID: 21917891 [PubMed - in process]

Related citations

------------------------------------------

J Infect Dis. 2011 Oct;204(8):1181-5.

Altered Expression of SHIP, a Toll-like Receptor Pathway Inhibitor, Is

Associated With the Severity of Liver Fibrosis in Chronic Hepatitis C Virus

Infection.

Katsounas A, Trippler M, Kottilil S, Lempicki RA, Gerken G, Schlaak JF.

Source

Department of Gastroenterology and Hepatology, University Hospital of Essen,

Essen 45147, Germany.

Abstract

Hepatitis C-related fibrogenesis has been shown to involve complex interactions

between peripheral and hepatic immune responses. Peripheral whole blood (PB)

samples from patients with chronic hepatitis C (n = 36) were subjected to

microarray analysis in order to identify gene expression patterns associated

with immune pathways in PB and hepatic fibrosis. Distinct regulation of gene

expression of inositol polyphosphate-5-phosphatase/145kDa (INPP5D or SHIP), a

TLR2/TLR4-inhibitor, and heat shock protein 8/22kDa (HSPB8), an endogenous

TLR4-ligand, during fibrogenesis was identified and could be confirmed by

quantitative reverse-transcription polymerase chain reaction. These results

suggest a potential link between peripheral activity of the TLR4-pathway,

peripheral SHIP-dependent immune regulation, and liver fibrosis.

PMID: 21917890 [PubMed - in process]

Related citations

---------------------------------------------

J Infect Dis. 2011 Oct;204(8):1172-80.

Monoclonal Antibody 2-152a Suppresses Hepatitis C Virus Infection Through

Betaine/GABA Transporter-1.

Satoh M, Saito M, Takano T, Kasama Y, Nishimura T, Nishito Y, Hirata Y, Arai M,

Sudoh M, Kai C, Kohara M, Tsukiyama-Kohara K.

Source

Department of Experimental Phylaxiology, Faculty of Life Sciences, Kumamoto

University, Honjo Kumamoto City.

Abstract

Background. We recently established a monoclonal antibody (2-152a MAb) that

binds to 3β-hydroxysterol-Δ24-reductase (DHCR24) by immunizing mice with cells

(RzM6-LC) persistently expressing hepatitis C virus (HCV). Here, we aimed to

analyze the activity of 2-152a MAb against HCV replication and explore the

molecular mechanism underlying the antiviral activity. Methods. We

characterized the effects of 2-152a MAb on HCV replication and performed a

microarray analysis of antibody-treated HCV replicon cells. The molecules

showing a significant change after the antibody treatment were screened to

examine their relationship with HCV replication. Results. The antibody had

antiviral activity both in vitro and in vivo (chimeric mice). In the microarray

analysis, 2-152a MAb significantly suppressed the expression of betaine/GABA

transporter-1 (BGT-1) in 2 HCV replicon cell lines but not in HCV-cured cells.

Silencing of BGT-1 expression by small interfering RNA (siRNA) revealed

significant suppression of HCV replication and infection without cytotoxicity.

Further, BGT-1 expression was significantly increased in the presence of HCV (P

< .05). Conclusions. Our results suggest that 2-152a MAb suppresses HCV

replication and infection through BGT-1. These findings highlight important

roles of BGT-1 in HCV replication and reveal a possible target for anti-HCV

therapy.

PMID: 21917889 [PubMed - in process]

Related citations

----------------------------------------------------------

J Med Virol. 2011 Nov;83(11):1930-7. doi: 10.1002/jmv.22168.

Clinical evaluation of the signal-to-cutoff ratios of hepatitis C virus antibody

screening tests used in China.

Wu S, Liu Y, Cheng L, Yin B, Peng J, Sun Z.

Source

Department of Clinical Laboratory, Tongji Hospital of Tongji Medical College,

Huazhong University of Science and Technology, Wuhan, Hubei, China.

Abstract

The clinical diagnosis of hepatitis C virus (HCV) infection is important to

direct an accurate course of therapy. Previous studies have reported a

correlation between the signal-to-cutoff (S/CO) ratios of the anti-HCV screening

test and confirm HCV infections for American anti-HCV screening kits as well as

for those in China. It is currently unknown whether clinical laboratories use

the same threshold S/CO ratios under routine conditions and if these values are

acceptable for the analysis of Chinese samples. A total of 336 anti-HCV

screening-test-positive serum samples were tested in duplicate using different

lots of three most commonly used enzyme immunoassay (EIA) kits available in

China. Samples were also tested using the Architect Anti-HCV chemiluminescent

microparticle immunoassay (CMIA) kit and measured for HCV RNA. Recombinant

immunoblot assays (RIBA) were additionally performed on samples with HCV

RNA-negative results with RIBA HCV 3.0. The relationship between S/CO ratios and

confirmed HCV infection rates were analyzed. The threshold S/CO ratio for each

screening kit correlated with the ≥95% positive predictive value was InTec

12.0, KHB 4.0, Wantai 5.0, and Abbott Architect 5.0. Therefore, the same

threshold S/CO ratios for manufactured domestically EIA kits was difficult to

attain. A multi-center study with a large sample size is required to identify a

uniform threshold S/CO ratio for use in different diagnostic laboratories.

Alternatively, individual laboratories may be required to establish threshold

S/CO ratios in their own laboratories to obtain consistent diagnostic results.

J. Med. Virol. 83:1930-1937, 2011. © 2011 Wiley-Liss, Inc.

Copyright © 2011 Wiley-Liss, Inc.

PMID: 21915868 [PubMed - in process]

Related citations

-------------------------------------------------------------

J Med Virol. 2011 Nov;83(11):1924-9. doi: 10.1002/jmv.22216.

Prevalence of Amino acid mutation in hepatitis C virus core region among

Japanese volunteer blood donors.

Furui Y, Hoshi Y, Murata K, Ito K, Suzuki K, Uchida S, Satake M, Mizokami M,

Tadokoro K.

Source

Central Blood Institute, Japanese Red Cross, Tokyo, Japan.

Abstract

It is not known whether there is a trend of increasing or decreasing incidence

of new hepatitis C virus (HCV) infections in Japan. From the treatment point of

view, it is important to verify HCV genotypes and the prevalence of

treatment-resistant clones of HCV. At the Japanese Red Cross blood centers, all

blood samples obtained from blood donation have been screened using serological

methods and the minipool nucleic acid amplification testing. One hundred and

fourteen donors have been identified over the past 10 years to be HCV RNA-only

positive without detectable anti-HCV and were considered to be in the acute

phase of HCV infection. There was a trend of decreasing incidence of such new

infections among the blood donors. HCV RNA-only-positive samples were examined

further for genotyping and HCV RNA quantitation. Genotype 2 (2a plus 2b) was

predominant (78.2%) among them followed by genotype 1b (21.2%). Direct

sequencing was carried out to detect the possible treatment-resistant mutant

clones 70Q and 91M, clones with amino acid substitutions at positions 70 and 91

of the HCV core protein, respectively. 70Q and 91M were found regularly in

donors with genotype 1b, but not in those with other genotypes. No particular

endemic areas for the mutant clones were identified. There was no significant

difference in the mean viral titer between the 70Q mutant type and the non-70Q

wild-type. Even in newly infected people, the mutant clone 70Q was detected

frequently. J. Med. Virol. 83:1924-1929, 2011. © 2011 Wiley-Liss, Inc.

Copyright © 2011 Wiley-Liss, Inc.

PMID: 21915867 [PubMed - in process]

[Guest guest]

J Infect Dis. 2011 Oct;204(8):1186-90.

Vaccine-induced cross-genotype reactive neutralizing antibodies against

hepatitis C virus.

Meunier JC, Gottwein JM, Houghton M, RS, Emerson SU, Bukh J, Purcell RH.

Source

Laboratory of Infectious Diseases, National Institute of Allergy and Infectious

Diseases, National Institutes of Health, Bethesda, land.

Abstract

We detected cross-reactive neutralizing antibodies (NtAb) against hepatitis C

virus (HCV) in chimpanzees vaccinated with HCV-1 (genotype 1a) recombinant E1/E2

envelope glycoproteins. Five vaccinated chimpanzees, protected following HCV-1

challenge, were initially studied using the heterologous H77 (genotype 1a) HCVpp

assay. All animals had developed NtAb after the second vaccination; 4 animals

had reciprocal titers of ≥200 at the time of challenge. Using genotypes 1a-6a

HCV pseudoparticles (HCVpp) and cell culture-derived HCV (HCVcc) assays,

cross-reactive NtAb were detected against 1a, 4a, 5a, and 6a, with limited

reactivity against 2a and 3a. Our study provides encouragement for the

development of a recombinant envelope-based vaccine against hepatitis C.

PMID: 21917891 [PubMed - in process]

Related citations

------------------------------------------

J Infect Dis. 2011 Oct;204(8):1181-5.

Altered Expression of SHIP, a Toll-like Receptor Pathway Inhibitor, Is

Associated With the Severity of Liver Fibrosis in Chronic Hepatitis C Virus

Infection.

Katsounas A, Trippler M, Kottilil S, Lempicki RA, Gerken G, Schlaak JF.

Source

Department of Gastroenterology and Hepatology, University Hospital of Essen,

Essen 45147, Germany.

Abstract

Hepatitis C-related fibrogenesis has been shown to involve complex interactions

between peripheral and hepatic immune responses. Peripheral whole blood (PB)

samples from patients with chronic hepatitis C (n = 36) were subjected to

microarray analysis in order to identify gene expression patterns associated

with immune pathways in PB and hepatic fibrosis. Distinct regulation of gene

expression of inositol polyphosphate-5-phosphatase/145kDa (INPP5D or SHIP), a

TLR2/TLR4-inhibitor, and heat shock protein 8/22kDa (HSPB8), an endogenous

TLR4-ligand, during fibrogenesis was identified and could be confirmed by

quantitative reverse-transcription polymerase chain reaction. These results

suggest a potential link between peripheral activity of the TLR4-pathway,

peripheral SHIP-dependent immune regulation, and liver fibrosis.

PMID: 21917890 [PubMed - in process]

Related citations

---------------------------------------------

J Infect Dis. 2011 Oct;204(8):1172-80.

Monoclonal Antibody 2-152a Suppresses Hepatitis C Virus Infection Through

Betaine/GABA Transporter-1.

Satoh M, Saito M, Takano T, Kasama Y, Nishimura T, Nishito Y, Hirata Y, Arai M,

Sudoh M, Kai C, Kohara M, Tsukiyama-Kohara K.

Source

Department of Experimental Phylaxiology, Faculty of Life Sciences, Kumamoto

University, Honjo Kumamoto City.

Abstract

Background. We recently established a monoclonal antibody (2-152a MAb) that

binds to 3β-hydroxysterol-Δ24-reductase (DHCR24) by immunizing mice with cells

(RzM6-LC) persistently expressing hepatitis C virus (HCV). Here, we aimed to

analyze the activity of 2-152a MAb against HCV replication and explore the

molecular mechanism underlying the antiviral activity. Methods. We

characterized the effects of 2-152a MAb on HCV replication and performed a

microarray analysis of antibody-treated HCV replicon cells. The molecules

showing a significant change after the antibody treatment were screened to

examine their relationship with HCV replication. Results. The antibody had

antiviral activity both in vitro and in vivo (chimeric mice). In the microarray

analysis, 2-152a MAb significantly suppressed the expression of betaine/GABA

transporter-1 (BGT-1) in 2 HCV replicon cell lines but not in HCV-cured cells.

Silencing of BGT-1 expression by small interfering RNA (siRNA) revealed

significant suppression of HCV replication and infection without cytotoxicity.

Further, BGT-1 expression was significantly increased in the presence of HCV (P

< .05). Conclusions. Our results suggest that 2-152a MAb suppresses HCV

replication and infection through BGT-1. These findings highlight important

roles of BGT-1 in HCV replication and reveal a possible target for anti-HCV

therapy.

PMID: 21917889 [PubMed - in process]

Related citations

----------------------------------------------------------

J Med Virol. 2011 Nov;83(11):1930-7. doi: 10.1002/jmv.22168.

Clinical evaluation of the signal-to-cutoff ratios of hepatitis C virus antibody

screening tests used in China.

Wu S, Liu Y, Cheng L, Yin B, Peng J, Sun Z.

Source

Department of Clinical Laboratory, Tongji Hospital of Tongji Medical College,

Huazhong University of Science and Technology, Wuhan, Hubei, China.

Abstract

The clinical diagnosis of hepatitis C virus (HCV) infection is important to

direct an accurate course of therapy. Previous studies have reported a

correlation between the signal-to-cutoff (S/CO) ratios of the anti-HCV screening

test and confirm HCV infections for American anti-HCV screening kits as well as

for those in China. It is currently unknown whether clinical laboratories use

the same threshold S/CO ratios under routine conditions and if these values are

acceptable for the analysis of Chinese samples. A total of 336 anti-HCV

screening-test-positive serum samples were tested in duplicate using different

lots of three most commonly used enzyme immunoassay (EIA) kits available in

China. Samples were also tested using the Architect Anti-HCV chemiluminescent

microparticle immunoassay (CMIA) kit and measured for HCV RNA. Recombinant

immunoblot assays (RIBA) were additionally performed on samples with HCV

RNA-negative results with RIBA HCV 3.0. The relationship between S/CO ratios and

confirmed HCV infection rates were analyzed. The threshold S/CO ratio for each

screening kit correlated with the ≥95% positive predictive value was InTec

12.0, KHB 4.0, Wantai 5.0, and Abbott Architect 5.0. Therefore, the same

threshold S/CO ratios for manufactured domestically EIA kits was difficult to

attain. A multi-center study with a large sample size is required to identify a

uniform threshold S/CO ratio for use in different diagnostic laboratories.

Alternatively, individual laboratories may be required to establish threshold

S/CO ratios in their own laboratories to obtain consistent diagnostic results.

J. Med. Virol. 83:1930-1937, 2011. © 2011 Wiley-Liss, Inc.

Copyright © 2011 Wiley-Liss, Inc.

PMID: 21915868 [PubMed - in process]

Related citations

-------------------------------------------------------------

J Med Virol. 2011 Nov;83(11):1924-9. doi: 10.1002/jmv.22216.

Prevalence of Amino acid mutation in hepatitis C virus core region among

Japanese volunteer blood donors.

Furui Y, Hoshi Y, Murata K, Ito K, Suzuki K, Uchida S, Satake M, Mizokami M,

Tadokoro K.

Source

Central Blood Institute, Japanese Red Cross, Tokyo, Japan.

Abstract

It is not known whether there is a trend of increasing or decreasing incidence

of new hepatitis C virus (HCV) infections in Japan. From the treatment point of

view, it is important to verify HCV genotypes and the prevalence of

treatment-resistant clones of HCV. At the Japanese Red Cross blood centers, all

blood samples obtained from blood donation have been screened using serological

methods and the minipool nucleic acid amplification testing. One hundred and

fourteen donors have been identified over the past 10 years to be HCV RNA-only

positive without detectable anti-HCV and were considered to be in the acute

phase of HCV infection. There was a trend of decreasing incidence of such new

infections among the blood donors. HCV RNA-only-positive samples were examined

further for genotyping and HCV RNA quantitation. Genotype 2 (2a plus 2b) was

predominant (78.2%) among them followed by genotype 1b (21.2%). Direct

sequencing was carried out to detect the possible treatment-resistant mutant

clones 70Q and 91M, clones with amino acid substitutions at positions 70 and 91

of the HCV core protein, respectively. 70Q and 91M were found regularly in

donors with genotype 1b, but not in those with other genotypes. No particular

endemic areas for the mutant clones were identified. There was no significant

difference in the mean viral titer between the 70Q mutant type and the non-70Q

wild-type. Even in newly infected people, the mutant clone 70Q was detected

frequently. J. Med. Virol. 83:1924-1929, 2011. © 2011 Wiley-Liss, Inc.

Copyright © 2011 Wiley-Liss, Inc.

PMID: 21915867 [PubMed - in process]

[Guest guest]

J Infect Dis. 2011 Oct;204(8):1186-90.

Vaccine-induced cross-genotype reactive neutralizing antibodies against

hepatitis C virus.

Meunier JC, Gottwein JM, Houghton M, RS, Emerson SU, Bukh J, Purcell RH.

Source

Laboratory of Infectious Diseases, National Institute of Allergy and Infectious

Diseases, National Institutes of Health, Bethesda, land.

Abstract

We detected cross-reactive neutralizing antibodies (NtAb) against hepatitis C

virus (HCV) in chimpanzees vaccinated with HCV-1 (genotype 1a) recombinant E1/E2

envelope glycoproteins. Five vaccinated chimpanzees, protected following HCV-1

challenge, were initially studied using the heterologous H77 (genotype 1a) HCVpp

assay. All animals had developed NtAb after the second vaccination; 4 animals

had reciprocal titers of ≥200 at the time of challenge. Using genotypes 1a-6a

HCV pseudoparticles (HCVpp) and cell culture-derived HCV (HCVcc) assays,

cross-reactive NtAb were detected against 1a, 4a, 5a, and 6a, with limited

reactivity against 2a and 3a. Our study provides encouragement for the

development of a recombinant envelope-based vaccine against hepatitis C.

PMID: 21917891 [PubMed - in process]

Related citations

------------------------------------------

J Infect Dis. 2011 Oct;204(8):1181-5.

Altered Expression of SHIP, a Toll-like Receptor Pathway Inhibitor, Is

Associated With the Severity of Liver Fibrosis in Chronic Hepatitis C Virus

Infection.

Katsounas A, Trippler M, Kottilil S, Lempicki RA, Gerken G, Schlaak JF.

Source

Department of Gastroenterology and Hepatology, University Hospital of Essen,

Essen 45147, Germany.

Abstract

Hepatitis C-related fibrogenesis has been shown to involve complex interactions

between peripheral and hepatic immune responses. Peripheral whole blood (PB)

samples from patients with chronic hepatitis C (n = 36) were subjected to

microarray analysis in order to identify gene expression patterns associated

with immune pathways in PB and hepatic fibrosis. Distinct regulation of gene

expression of inositol polyphosphate-5-phosphatase/145kDa (INPP5D or SHIP), a

TLR2/TLR4-inhibitor, and heat shock protein 8/22kDa (HSPB8), an endogenous

TLR4-ligand, during fibrogenesis was identified and could be confirmed by

quantitative reverse-transcription polymerase chain reaction. These results

suggest a potential link between peripheral activity of the TLR4-pathway,

peripheral SHIP-dependent immune regulation, and liver fibrosis.

PMID: 21917890 [PubMed - in process]

Related citations

---------------------------------------------

J Infect Dis. 2011 Oct;204(8):1172-80.

Monoclonal Antibody 2-152a Suppresses Hepatitis C Virus Infection Through

Betaine/GABA Transporter-1.

Satoh M, Saito M, Takano T, Kasama Y, Nishimura T, Nishito Y, Hirata Y, Arai M,

Sudoh M, Kai C, Kohara M, Tsukiyama-Kohara K.

Source

Department of Experimental Phylaxiology, Faculty of Life Sciences, Kumamoto

University, Honjo Kumamoto City.

Abstract

Background. We recently established a monoclonal antibody (2-152a MAb) that

binds to 3β-hydroxysterol-Δ24-reductase (DHCR24) by immunizing mice with cells

(RzM6-LC) persistently expressing hepatitis C virus (HCV). Here, we aimed to

analyze the activity of 2-152a MAb against HCV replication and explore the

molecular mechanism underlying the antiviral activity. Methods. We

characterized the effects of 2-152a MAb on HCV replication and performed a

microarray analysis of antibody-treated HCV replicon cells. The molecules

showing a significant change after the antibody treatment were screened to

examine their relationship with HCV replication. Results. The antibody had

antiviral activity both in vitro and in vivo (chimeric mice). In the microarray

analysis, 2-152a MAb significantly suppressed the expression of betaine/GABA

transporter-1 (BGT-1) in 2 HCV replicon cell lines but not in HCV-cured cells.

Silencing of BGT-1 expression by small interfering RNA (siRNA) revealed

significant suppression of HCV replication and infection without cytotoxicity.

Further, BGT-1 expression was significantly increased in the presence of HCV (P

< .05). Conclusions. Our results suggest that 2-152a MAb suppresses HCV

replication and infection through BGT-1. These findings highlight important

roles of BGT-1 in HCV replication and reveal a possible target for anti-HCV

therapy.

PMID: 21917889 [PubMed - in process]

Related citations

----------------------------------------------------------

J Med Virol. 2011 Nov;83(11):1930-7. doi: 10.1002/jmv.22168.

Clinical evaluation of the signal-to-cutoff ratios of hepatitis C virus antibody

screening tests used in China.

Wu S, Liu Y, Cheng L, Yin B, Peng J, Sun Z.

Source

Department of Clinical Laboratory, Tongji Hospital of Tongji Medical College,

Huazhong University of Science and Technology, Wuhan, Hubei, China.

Abstract

The clinical diagnosis of hepatitis C virus (HCV) infection is important to

direct an accurate course of therapy. Previous studies have reported a

correlation between the signal-to-cutoff (S/CO) ratios of the anti-HCV screening

test and confirm HCV infections for American anti-HCV screening kits as well as

for those in China. It is currently unknown whether clinical laboratories use

the same threshold S/CO ratios under routine conditions and if these values are

acceptable for the analysis of Chinese samples. A total of 336 anti-HCV

screening-test-positive serum samples were tested in duplicate using different

lots of three most commonly used enzyme immunoassay (EIA) kits available in

China. Samples were also tested using the Architect Anti-HCV chemiluminescent

microparticle immunoassay (CMIA) kit and measured for HCV RNA. Recombinant

immunoblot assays (RIBA) were additionally performed on samples with HCV

RNA-negative results with RIBA HCV 3.0. The relationship between S/CO ratios and

confirmed HCV infection rates were analyzed. The threshold S/CO ratio for each

screening kit correlated with the ≥95% positive predictive value was InTec

12.0, KHB 4.0, Wantai 5.0, and Abbott Architect 5.0. Therefore, the same

threshold S/CO ratios for manufactured domestically EIA kits was difficult to

attain. A multi-center study with a large sample size is required to identify a

uniform threshold S/CO ratio for use in different diagnostic laboratories.

Alternatively, individual laboratories may be required to establish threshold

S/CO ratios in their own laboratories to obtain consistent diagnostic results.

J. Med. Virol. 83:1930-1937, 2011. © 2011 Wiley-Liss, Inc.

Copyright © 2011 Wiley-Liss, Inc.

PMID: 21915868 [PubMed - in process]

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J Med Virol. 2011 Nov;83(11):1924-9. doi: 10.1002/jmv.22216.

Prevalence of Amino acid mutation in hepatitis C virus core region among

Japanese volunteer blood donors.

Furui Y, Hoshi Y, Murata K, Ito K, Suzuki K, Uchida S, Satake M, Mizokami M,

Tadokoro K.

Source

Central Blood Institute, Japanese Red Cross, Tokyo, Japan.

Abstract

It is not known whether there is a trend of increasing or decreasing incidence

of new hepatitis C virus (HCV) infections in Japan. From the treatment point of

view, it is important to verify HCV genotypes and the prevalence of

treatment-resistant clones of HCV. At the Japanese Red Cross blood centers, all

blood samples obtained from blood donation have been screened using serological

methods and the minipool nucleic acid amplification testing. One hundred and

fourteen donors have been identified over the past 10 years to be HCV RNA-only

positive without detectable anti-HCV and were considered to be in the acute

phase of HCV infection. There was a trend of decreasing incidence of such new

infections among the blood donors. HCV RNA-only-positive samples were examined

further for genotyping and HCV RNA quantitation. Genotype 2 (2a plus 2b) was

predominant (78.2%) among them followed by genotype 1b (21.2%). Direct

sequencing was carried out to detect the possible treatment-resistant mutant

clones 70Q and 91M, clones with amino acid substitutions at positions 70 and 91

of the HCV core protein, respectively. 70Q and 91M were found regularly in

donors with genotype 1b, but not in those with other genotypes. No particular

endemic areas for the mutant clones were identified. There was no significant

difference in the mean viral titer between the 70Q mutant type and the non-70Q

wild-type. Even in newly infected people, the mutant clone 70Q was detected

frequently. J. Med. Virol. 83:1924-1929, 2011. © 2011 Wiley-Liss, Inc.

Copyright © 2011 Wiley-Liss, Inc.

PMID: 21915867 [PubMed - in process]