Coinfection of Hepatic Cell Lines with Human Immunodeficiency Virus and Hepatitis B Virus Leads to an Increase in Intracellular Hepatitis B Surface Antigen
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作者:
Iser, David M.
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Alfred Hosp, Infect Dis Unit, Melbourne, Vic 3004, Australia
Univ Melbourne, Dept Med, St Vincents Hosp, Melbourne, Vic, AustraliaAlfred Hosp, Infect Dis Unit, Melbourne, Vic 3004, Australia
Iser, David M.
[1
,2
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Warner, Nadia
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机构:
Victorian Infect Dis Reference Lab, Dept Res & Mol Dev, Melbourne, Vic, AustraliaAlfred Hosp, Infect Dis Unit, Melbourne, Vic 3004, Australia
Warner, Nadia
[3
]
Revill, Peter A.
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Victorian Infect Dis Reference Lab, Dept Res & Mol Dev, Melbourne, Vic, AustraliaAlfred Hosp, Infect Dis Unit, Melbourne, Vic 3004, Australia
Revill, Peter A.
[3
]
Solomon, Ajantha
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机构:
Monash Univ, Dept Med, Melbourne, Vic 3004, AustraliaAlfred Hosp, Infect Dis Unit, Melbourne, Vic 3004, Australia
Solomon, Ajantha
[4
]
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机构:
Wightman, Fiona
[4
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Saleh, Suha
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Monash Univ, Dept Med, Melbourne, Vic 3004, AustraliaAlfred Hosp, Infect Dis Unit, Melbourne, Vic 3004, Australia
Saleh, Suha
[4
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Crane, Megan
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Monash Univ, Dept Med, Melbourne, Vic 3004, AustraliaAlfred Hosp, Infect Dis Unit, Melbourne, Vic 3004, Australia
Crane, Megan
[4
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Cameron, Paul U.
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Alfred Hosp, Infect Dis Unit, Melbourne, Vic 3004, Australia
Monash Univ, Dept Med, Melbourne, Vic 3004, AustraliaAlfred Hosp, Infect Dis Unit, Melbourne, Vic 3004, Australia
Cameron, Paul U.
[1
,4
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Bowden, Scott
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Victorian Infect Dis Reference Lab, Dept Res & Mol Dev, Melbourne, Vic, AustraliaAlfred Hosp, Infect Dis Unit, Melbourne, Vic 3004, Australia
Bowden, Scott
[3
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Nguyen, Tin
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Victorian Infect Dis Reference Lab, Dept Res & Mol Dev, Melbourne, Vic, AustraliaAlfred Hosp, Infect Dis Unit, Melbourne, Vic 3004, Australia
Nguyen, Tin
[3
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Pereira, Candida F.
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机构:
Monash Univ, Dept Med, Melbourne, Vic 3004, Australia
Burnet Inst, Ctr Virol, Melbourne, Vic, Australia
Monash Univ, Monash Micro Imaging, Clayton, Vic 3800, AustraliaAlfred Hosp, Infect Dis Unit, Melbourne, Vic 3004, Australia
Pereira, Candida F.
[4
,5
,6
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Desmond, Paul V.
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Univ Melbourne, Dept Med, St Vincents Hosp, Melbourne, Vic, AustraliaAlfred Hosp, Infect Dis Unit, Melbourne, Vic 3004, Australia
Desmond, Paul V.
[2
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Locarnini, Stephen A.
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Victorian Infect Dis Reference Lab, Dept Res & Mol Dev, Melbourne, Vic, AustraliaAlfred Hosp, Infect Dis Unit, Melbourne, Vic 3004, Australia
Locarnini, Stephen A.
[3
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Lewin, Sharon R.
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机构:
Alfred Hosp, Infect Dis Unit, Melbourne, Vic 3004, Australia
Monash Univ, Dept Med, Melbourne, Vic 3004, Australia
Burnet Inst, Ctr Virol, Melbourne, Vic, AustraliaAlfred Hosp, Infect Dis Unit, Melbourne, Vic 3004, Australia
Lewin, Sharon R.
[1
,4
,5
]
机构:
[1] Alfred Hosp, Infect Dis Unit, Melbourne, Vic 3004, Australia
[2] Univ Melbourne, Dept Med, St Vincents Hosp, Melbourne, Vic, Australia
[3] Victorian Infect Dis Reference Lab, Dept Res & Mol Dev, Melbourne, Vic, Australia
[4] Monash Univ, Dept Med, Melbourne, Vic 3004, Australia
[5] Burnet Inst, Ctr Virol, Melbourne, Vic, Australia
[6] Monash Univ, Monash Micro Imaging, Clayton, Vic 3800, Australia
Liver-related mortality is increased in the setting of HIV-hepatitis B virus (HBV) coinfection. However, interactions between HIV and HBV to explain this observation have not been described. We hypothesized that HIV infection of hepatocytes directly affects the life cycle of HBV. We infected human hepatic cell lines expressing HBV (Hep3B and AD38 cells) or not expressing HBV (Huh7, HepG2, and AD43 cells) with laboratory strains of HIV (NL4-3 and AD8), as well as a vesicular stomatitis virus (VSV)-pseudotyped HIV expressing enhanced green fluorescent protein (EGFP). Following HIV infection with NL4-3 or AD8 in hepatic cell lines, we observed a significant increase in HIV reverse transcriptase activity which was infectious. Despite no detection of surface CD4, CCR5, and CXCR4 by flow cytometry, AD8 infection of AD38 cells was inhibited by maraviroc and NL4-3 was inhibited by AMD3100, demonstrating that HIV enters AD38 hepatic cell lines via CCR5 or CXCR4. High-level infection of AD38 cells (50%) was achieved using VSV-pseudotyped HIV. Co-infection of the AD38 cell line with HIV did not alter the HBV DNA amount or species as determined by Southern blotting or nucleic acid signal amplification. However, coinfection with HIV was associated with a significant increase in intracellular HBsAg when measured by Western blotting, quantitative HBsAg, and fluorescence microscopy. We conclude that HIV infection of HBV-infected hepatic cell lines significantly increased intracellular HBsAg but not HBV DNA synthesis and that increased intrahepatic HBsAg secondary to direct infection by HIV may contribute to accelerated liver disease in HIV-HBV-coinfected individuals.
机构:
Wuhan Univ, Coll Life Sci, Wuhan 430072, Peoples R ChinaWuhan Univ, Coll Life Sci, Wuhan 430072, Peoples R China
Pan, Wei
Wu, Zuoqiao
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Wuhan Univ, Coll Life Sci, Wuhan 430072, Peoples R ChinaWuhan Univ, Coll Life Sci, Wuhan 430072, Peoples R China
Wu, Zuoqiao
Wu, Shuwen
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Wuhan Univ, Coll Life Sci, Wuhan 430072, Peoples R ChinaWuhan Univ, Coll Life Sci, Wuhan 430072, Peoples R China
Wu, Shuwen
Guo, Deyin
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Wuhan Univ, Coll Life Sci, Wuhan 430072, Peoples R ChinaWuhan Univ, Coll Life Sci, Wuhan 430072, Peoples R China
Guo, Deyin
Gong, Xiaoyan
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Wuhan Univ, Coll Chem & Mol Sci, Wuhan 430072, Peoples R ChinaWuhan Univ, Coll Life Sci, Wuhan 430072, Peoples R China
Gong, Xiaoyan
Po, Tien
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Wuhan Univ, Coll Life Sci, Wuhan 430072, Peoples R China
Chinese Acad Sci, Inst Microbiol, Beijing, Peoples R ChinaWuhan Univ, Coll Life Sci, Wuhan 430072, Peoples R China
机构:
Univ Chicago, Med Ctr, Dept Infect Dis & Global Hlth, Chicago, IL 60637 USAUniv Chicago, Med Ctr, Dept Infect Dis & Global Hlth, Chicago, IL 60637 USA
Petty, Lindsay A.
Steinbeck, Jennifer L.
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Univ Chicago, Med Ctr, Dept Infect Dis & Global Hlth, Chicago, IL 60637 USAUniv Chicago, Med Ctr, Dept Infect Dis & Global Hlth, Chicago, IL 60637 USA
Steinbeck, Jennifer L.
Purse, Kenneth
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Univ Chicago, Med Ctr, Dept Infect Dis & Global Hlth, Chicago, IL 60637 USAUniv Chicago, Med Ctr, Dept Infect Dis & Global Hlth, Chicago, IL 60637 USA
Purse, Kenneth
Jensen, Donald M.
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机构:
Univ Chicago, Med Ctr, Dept Med, Ctr Liver Dis, Chicago, IL 60637 USAUniv Chicago, Med Ctr, Dept Infect Dis & Global Hlth, Chicago, IL 60637 USA
机构:
Chinese Acad Med Sci, Peking Union Med Coll, Dept Infect Dis, Peking Union Med Coll Hosp, Beijing 100730, Peoples R ChinaChinese Acad Med Sci, Peking Union Med Coll, Dept Infect Dis, Peking Union Med Coll Hosp, Beijing 100730, Peoples R China
Li Yi-jia
Wang Huan-ling
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Chinese Acad Med Sci, Peking Union Med Coll, Dept Infect Dis, Peking Union Med Coll Hosp, Beijing 100730, Peoples R ChinaChinese Acad Med Sci, Peking Union Med Coll, Dept Infect Dis, Peking Union Med Coll Hosp, Beijing 100730, Peoples R China
Wang Huan-ling
Li Tai-sheng
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Chinese Acad Med Sci, Peking Union Med Coll, Dept Infect Dis, Peking Union Med Coll Hosp, Beijing 100730, Peoples R ChinaChinese Acad Med Sci, Peking Union Med Coll, Dept Infect Dis, Peking Union Med Coll Hosp, Beijing 100730, Peoples R China
机构:
Univ Maryland, Sch Med, Inst Human Virol, Div Clin Care & Res, Baltimore, MD 21201 USAUniv Maryland, Sch Med, Inst Human Virol, Div Clin Care & Res, Baltimore, MD 21201 USA
Jakharia, Niyati
Kottilil, Shyam
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Univ Maryland, Sch Med, Inst Human Virol, Div Clin Care & Res, Baltimore, MD 21201 USAUniv Maryland, Sch Med, Inst Human Virol, Div Clin Care & Res, Baltimore, MD 21201 USA
Kottilil, Shyam
Chua, Joel V.
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Univ Maryland, Sch Med, Inst Human Virol, Div Clin Care & Res, Baltimore, MD 21201 USAUniv Maryland, Sch Med, Inst Human Virol, Div Clin Care & Res, Baltimore, MD 21201 USA
机构:
Nagoya Med Ctr, Dept Gastroenterol, Natl Hosp Org, Nagoya, Aichi 4600001, Japan
Nagoya City Univ, Grad Sch Med Sci, Dept Virol, Nagoya, Aichi 4678602, Japan
Nagoya City Univ, Grad Sch Med Sci, Liver Unit, Nagoya, Aichi 4678602, JapanNagoya Med Ctr, Dept Gastroenterol, Natl Hosp Org, Nagoya, Aichi 4600001, Japan
Urata, Noboru
Watanabe, Tsunamasa
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机构:
St Marianna Univ, Sch Med, Dept Internal Med, Div Gastroenterol & Hepatol, Kawasaki, Kanagawa 2168511, JapanNagoya Med Ctr, Dept Gastroenterol, Natl Hosp Org, Nagoya, Aichi 4600001, Japan
Watanabe, Tsunamasa
Hirashima, Noboru
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Nagoya Med Ctr, Dept Gastroenterol, Natl Hosp Org, Nagoya, Aichi 4600001, JapanNagoya Med Ctr, Dept Gastroenterol, Natl Hosp Org, Nagoya, Aichi 4600001, Japan
Hirashima, Noboru
Yokomaku, Yoshiyuki
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Nagoya Med Ctr, Dept Infect Dis & Immunol, Natl Hosp Org, Nagoya, Aichi 4600001, JapanNagoya Med Ctr, Dept Gastroenterol, Natl Hosp Org, Nagoya, Aichi 4600001, Japan
Yokomaku, Yoshiyuki
Imamura, Junji
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机构:
Nagoya Med Ctr, Dept Infect Dis & Immunol, Natl Hosp Org, Nagoya, Aichi 4600001, Japan
Sendai Med Ctr, Natl Hosp Org, Dept Infect Dis & Immunol, Sendai, Miyagi 9838520, JapanNagoya Med Ctr, Dept Gastroenterol, Natl Hosp Org, Nagoya, Aichi 4600001, Japan
Imamura, Junji
Iwatani, Yasumasa
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Nagoya Med Ctr, Dept Infect Dis & Immunol, Natl Hosp Org, Nagoya, Aichi 4600001, JapanNagoya Med Ctr, Dept Gastroenterol, Natl Hosp Org, Nagoya, Aichi 4600001, Japan
Iwatani, Yasumasa
Shimada, Masaaki
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Nagoya Med Ctr, Dept Gastroenterol, Natl Hosp Org, Nagoya, Aichi 4600001, JapanNagoya Med Ctr, Dept Gastroenterol, Natl Hosp Org, Nagoya, Aichi 4600001, Japan
Shimada, Masaaki
Tanaka, Yasuhito
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机构:
Nagoya City Univ, Grad Sch Med Sci, Dept Virol, Nagoya, Aichi 4678602, Japan
Nagoya City Univ, Grad Sch Med Sci, Liver Unit, Nagoya, Aichi 4678602, Japan
Kumamoto Univ, Dept Gastroenterol & Hepatol, Fac Life Sci, Kumamoto 8608556, JapanNagoya Med Ctr, Dept Gastroenterol, Natl Hosp Org, Nagoya, Aichi 4600001, Japan