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4. Intrinsic Immunity Shapes Viral Resistance of Stem Cells

Author

Wu, Xianfang, Thi, Viet Loan Dao, Huang, Yumin, Billerbeck, Eva, Saha, Debjani, Hoffmann, Hans-Heinrich, Wang, Yaomei, Silva, Luis A Vale, Sarbanes, Stephanie, Sun, Tony, Andrus, Linda, Yu, Yingpu, Quirk, Corrine, Li, Melody, MacDonald, Margaret R, Schneider, William M, An, Xiuli, Rosenberg, Brad R, and Rice, Charles M

Subjects
Medical Microbiology, Biomedical and Clinical Sciences, Biological Sciences, Biodefense, Infectious Diseases, Regenerative Medicine, Stem Cell Research - Nonembryonic - Human, Vaccine Related, Prevention, Stem Cell Research, Stem Cell Research - Nonembryonic - Non-Human, Emerging Infectious Diseases, Genetics, Underpinning research, Development of treatments and therapeutic interventions, 5.2 Cellular and gene therapies, 1.1 Normal biological development and functioning, Inflammatory and immune system, Infection, Animals, Cells, Cultured, Female, HEK293 Cells, Humans, Immunity, Innate, Interferons, Male, Mice, Mice, Inbred NOD, Pluripotent Stem Cells, Species Specificity, Virus Diseases, antiviral mechanisms, interferon-stimulated genes, intrinsic immunity, stem cell differentiation, tissue stem cells, tissue tropism, viral infection, Medical and Health Sciences, Developmental Biology, Biological sciences, Biomedical and clinical sciences
Abstract

Stem cells are highly resistant to viral infection compared to their differentiated progeny; however, the mechanism is mysterious. Here, we analyzed gene expression in mammalian stem cells and cells at various stages of differentiation. We find that, conserved across species, stem cells express a subset of genes previously classified as interferon (IFN) stimulated genes (ISGs) but that expression is intrinsic, as stem cells are refractory to interferon. This intrinsic ISG expression varies in a cell-type-specific manner, and many ISGs decrease upon differentiation, at which time cells become IFN responsive, allowing induction of a broad spectrum of ISGs by IFN signaling. Importantly, we show that intrinsically expressed ISGs protect stem cells against viral infection. We demonstrate the in vivo importance of intrinsic ISG expression for protecting stem cells and their differentiation potential during viral infection. These findings have intriguing implications for understanding stem cell biology and the evolution of pathogen resistance.

Published
2018

5. A Combination of Human Broadly Neutralizing Antibodies against Hepatitis B Virus HBsAg with Distinct Epitopes Suppresses Escape Mutations

Author

Wang, Qiao, Michailidis, Eleftherios, Yu, Yingpu, Wang, Zijun, Hurley, Arlene M., Oren, Deena A., Mayer, Christian T., Gazumyan, Anna, Liu, Zhenmi, Zhou, Yunjiao, Schoofs, Till, Yao, Kai-hui, Nieke, Jan P., Wu, Jianbo, Jiang, Qingling, Zou, Chenhui, Kabbani, Mohanmmad, Quirk, Corrine, Oliveira, Thiago, Chhosphel, Kalsang, Zhang, Qianqian, Schneider, William M., Jahan, Cyprien, Ying, Tianlei, Horowitz, Jill, Caskey, Marina, Jankovic, Mila, Robbiani, Davide F., Wen, Yumei, de Jong, Ype P., Rice, Charles M., and Nussenzweig, Michel C.

Published
2020
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7. A Draft Sequence for the Genome of the Domesticated Silkworm (Bombyx mori)

Author

Xia, Qingyou, Zhou, Zeyang, Lu, Cheng, Cheng, Daojun, Dai, Fangyin, Li, Bin, Zhao, Ping, Zha, Xingfu, Cheng, Tingcai, Chai, Chunli, Pan, Guoqing, Xu, Jinshan, Liu, Chun, Lin, Ying, Qian, Jifeng, Hou, Yong, Wu, Zhengli, Li, Guanrong, Pan, Minhui, Li, Chunfeng, Shen, Yihong, Lan, Xiqian, Yuan, Lianwei, Li, Tian, Xu, Hanfu, Yang, Guangwei, Wan, Yongji, Zhu, Yong, Yu, Maode, Shen, Weide, Wu, Dayang, Xiang, Zhonghuai, Yu, Jun, Wang, Jun, Li, Ruiqiang, Shi, Jianping, Li, Heng, Li, Guangyuan, Su, Jianning, Wang, Xiaoling, Li, Guoqing, Zhang, Zengjin, Wu, Qingfa, Li, Jun, Zhang, Qingpeng, Wei, Ning, Xu, Jianzhe, Sun, Haibo, Dong, Le, Liu, Dongyuan, Zhao, Shengli, Zhao, Xiaolan, Meng, Qingshun, Lan, Fengdi, Huang, Xiangang, Li, Yuanzhe, Fang, Lin, Li, Changfeng, Li, Dawei, Sun, Yongqiao, Zhang, Zhenpeng, Yang, Zheng, Huang, Yanqing, Qi, Qiuhui, He, Dandan, Huang, Haiyan, Zhang, Xiaowei, Wang, Zhiqiang, Li, Wenjie, Cao, Yuzhu, Yu, Yingpu, Yu, Hong, Li, Jinhong, Ye, Jiehua, Chen, Huan, Zhou, Yan, Liu, Bin, Wang, Jing, Ye, Jia, Ji, Hai, Li, Shengting, Ni, Peixiang, Zhang, Jianguo, Zhang, Yong, Zheng, Hongkun, Mao, Bingyu, Wang, Wen, Ye, Chen, Li, Songgang, Wang, Jian, Wong, Gane Ka-Shu, and Yang, Huanming

Published
2004

8. An RNA-based system to study hepatitis B virus replication and evaluate antivirals

Author

Yu, Yingpu, primary, Schneider, William M., additional, Kass, Maximilian A., additional, Michailidis, Eleftherios, additional, Acevedo, Ashley, additional, Pamplona Mosimann, Ana L., additional, Bordignon, Juliano, additional, Koenig, Alexander, additional, Livingston, Christine M., additional, van Gijzel, Hardeep, additional, Ni, Yi, additional, Ambrose, Pradeep M., additional, Freije, Catherine A., additional, Zhang, Mengyin, additional, Zou, Chenhui, additional, Kabbani, Mohammad, additional, Quirk, Corrine, additional, Jahan, Cyprien, additional, Wu, Xianfang, additional, Urban, Stephan, additional, You, Shihyun, additional, Shlomai, Amir, additional, de Jong, Ype P., additional, and Rice, Charles M., additional

Published
2023
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14. Replication and single-cycle delivery of SARS-CoV-2 replicons

Author

Ricardo-Lax, Inna, primary, Luna, Joseph M., additional, Thao, Tran Thi Nhu, additional, Le Pen, Jérémie, additional, Yu, Yingpu, additional, Hoffmann, H.-Heinrich, additional, Schneider, William M., additional, Razooky, Brandon S., additional, Fernandez-Martinez, Javier, additional, Schmidt, Fabian, additional, Weisblum, Yiska, additional, Trüeb, Bettina Salome, additional, Berenguer Veiga, Inês, additional, Schmied, Kimberly, additional, Ebert, Nadine, additional, Michailidis, Eleftherios, additional, Peace, Avery, additional, Sánchez-Rivera, Francisco J., additional, Lowe, Scott W., additional, Rout, Michael P., additional, Hatziioannou, Theodora, additional, Bieniasz, Paul D., additional, Poirier, John T., additional, MacDonald, Margaret R., additional, Thiel, Volker, additional, and Rice, Charles M., additional

Published
2021
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17. Public broadly neutralizing antibodies against hepatitis B virus in individuals with elite serologic activity

Author

Wang, Qiao, primary, Michailidis, Eleftherios, additional, Yu, Yingpu, additional, Wang, Zijun, additional, Hurley, Arlene M., additional, Oren, Deena A., additional, Mayer, Christian T., additional, Gazumyan, Anna, additional, Liu, Zhenmi, additional, Zhou, Yunjiao, additional, Schoofs, Till, additional, Yao, Kai-hui, additional, Nieke, Jan P., additional, Wu, Jianbo, additional, Jiang, Qingling, additional, Zou, Chenhui, additional, Kabbani, Mohanmmad, additional, Quirk, Corrine, additional, Oliveira, Thiago, additional, Chhosphel, Kalsang, additional, Zhang, Qianqian, additional, Schneider, William M., additional, Jahan, Cyprien, additional, Ying, Tianlei, additional, Horowitz, Jill, additional, Caskey, Marina, additional, Jankovic, Mila, additional, Robbiani, Davide F., additional, Wen, Yumei, additional, de Jong, Ype P., additional, Rice, Charles M., additional, and Nussenzweig, Michel C., additional

Published
2020
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19. SAT-188-Expansion and genetic modification of primary hepatocytes to study long-term hepatitis B virus infection

Author

Michailidis, Eleftherios, primary, Park, Paul, additional, Kabbani, Mohammad, additional, Silva, Liliana Mancio, additional, Yu, Yingpu, additional, Schneider, William M., additional, Andrus, Linda, additional, Zou, Chenhui, additional, Vercauteren, Koen, additional, Jahan, Cyprien, additional, Razooky, Brandon, additional, Quirk, Corrine, additional, Shlomai, Amir, additional, Bhatia, Sangeeta, additional, Rice, Charles, additional, and de Jong, Ype P., additional

Published
2019
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20. Correction: miRNA independent hepacivirus variants suggest a strong evolutionary pressure to maintain miR-122 dependence

Author

Yu, Yingpu, primary, Scheel, Troels K. H., additional, Luna, Joseph M., additional, Chung, Hachung, additional, Nishiuchi, Eiko, additional, Scull, Margaret A., additional, Echeverría, Natalia, additional, Ricardo-Lax, Inna, additional, Kapoor, Amit, additional, Lipkin, W. Ian, additional, Divers, Thomas J., additional, Antczak, Douglas F., additional, Tennant, Bud C., additional, and Rice, Charles M., additional

Published
2018
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21. miRNA independent hepacivirus variants suggest a strong evolutionary pressure to maintain miR-122 dependence

Author

Yu, Yingpu, primary, Scheel, Troels K. H., additional, Luna, Joseph M., additional, Chung, Hachung, additional, Nishiuchi, Eiko, additional, Scull, Margaret A., additional, Echeverría, Natalia, additional, Ricardo-Lax, Inna, additional, Kapoor, Amit, additional, Lipkin, Ian W., additional, Divers, Thomas J., additional, Antczak, Douglas F., additional, Tennant, Bud C., additional, and Rice, Charles M., additional

Published
2017
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22. miRNA independent hepacivirus variants suggest a strong evolutionary pressure to maintain miR-122 dependence

Author

Yu, Yingpu, Scheel, Troels K.H., Luna, Joseph M., Chung, Hachung, Nishiuchi, Eiko, Scull, Margaret A., Echeverría, Natalia, Ricardo-Lax, Inna, Kapoor, Amit, Lipkin, Ian W., Divers, Thomas J., Antczak, Douglas F., Tennant, Bud C., Rice, Charles M., Yu, Yingpu, Scheel, Troels K.H., Luna, Joseph M., Chung, Hachung, Nishiuchi, Eiko, Scull, Margaret A., Echeverría, Natalia, Ricardo-Lax, Inna, Kapoor, Amit, Lipkin, Ian W., Divers, Thomas J., Antczak, Douglas F., Tennant, Bud C., and Rice, Charles M.

Abstract

Hepatitis C virus (HCV) requires the liver specific micro-RNA (miRNA), miR-122, to replicate. This was considered unique among RNA viruses until recent discoveries of HCV-related hepaciviruses prompting the question of a more general miR-122 dependence. Among hepaciviruses, the closest known HCV relative is the equine non-primate hepacivirus (NPHV). Here, we used Argonaute cross-linking immunoprecipitation (AGO-CLIP) to confirm AGO binding to the single predicted miR-122 site in the NPHV 5’UTR in vivo. To study miR-122 requirements in the absence of NPHV-permissive cell culture systems, we generated infectious NPHV/HCV chimeric viruses with the 5’ end of NPHV replacing orthologous HCV sequences. These chimeras were viable even in cells lacking miR-122, although miR-122 presence enhanced virus production. No other miRNAs bound this region. By random mutagenesis, we isolated HCV variants partially dependent on miR-122 as well as robustly replicating NPHV/HCV variants completely independent of any miRNAs. These miRNA independent variants even replicate and produce infectious particles in non-hepatic cells after exogenous delivery of apolipoprotein E (ApoE). Our findings suggest that miR-122 independent HCV and NPHV variants have arisen and been sampled during evolution, yet miR-122 dependence has prevailed. We propose that hepaciviruses may use this mechanism to guarantee liver tropism and exploit the tolerogenic liver environment to avoid clearance and promote chronicity.

Published
2017

23. Characterization of nonprimate hepacivirus and construction of a functional molecular clone

Author

Scheel, Troels K H, Kapoor, Amit, Nishiuchi, Eiko, Brock, Kenny V, Yu, Yingpu, Andrus, Linda, Gu, Meigang, Renshaw, Randall W, Dubovi, Edward J, McDonough, Sean P, Van de Walle, Gerlinde R, Lipkin, W Ian, Divers, Thomas J, Tennant, Bud C, Rice, Charles M, Scheel, Troels K H, Kapoor, Amit, Nishiuchi, Eiko, Brock, Kenny V, Yu, Yingpu, Andrus, Linda, Gu, Meigang, Renshaw, Randall W, Dubovi, Edward J, McDonough, Sean P, Van de Walle, Gerlinde R, Lipkin, W Ian, Divers, Thomas J, Tennant, Bud C, and Rice, Charles M

Abstract

Nonprimate hepacivirus (NPHV) is the closest known relative of hepatitis C virus (HCV) and its study could enrich our understanding of HCV evolution, immunity, and pathogenesis. High seropositivity is found in horses worldwide with ∼ 3% viremic. NPHV natural history and molecular virology remain largely unexplored, however. Here, we show that NPHV, like HCV, can cause persistent infection for over a decade, with high titers and negative strand RNA in the liver. NPHV is a near-universal contaminant of commercial horse sera for cell culture. The complete NPHV 3'-UTR was determined and consists of interspersed homopolymer tracts and an HCV-like 3'-terminal poly(U)-X-tail. NPHV translation is stimulated by miR-122 and the 3'-UTR and, similar to HCV, the NPHV NS3-4A protease can cleave mitochondrial antiviral-signaling protein to inactivate the retinoic acid-inducible gene I pathway. Using an NPHV consensus cDNA clone, replication was not observed in primary equine fetal liver cultures or after electroporation of selectable replicons. However, intrahepatic RNA inoculation of a horse initiated infection, yielding high RNA titers in the serum and liver. Delayed seroconversion, slightly elevated circulating liver enzymes and mild hepatitis was observed, followed by viral clearance. This establishes the molecular components of a functional NPHV genome. Thus, NPHV appears to resemble HCV not only in genome structure but also in its ability to establish chronic infection with delayed seroconversion and hepatitis. This NPHV infectious clone and resulting acute phase sera will facilitate more detailed studies on the natural history, pathogenesis, and immunity of this novel hepacivirus in its natural host.

Published
2015

25. A genetic variation map for chicken with 2.8 million single-nucleotide polymorphisms.

Author

Wong, Gane Ka-Shu, Liu, Bin, Wang, Jun, Zhang, Yong, Yang, Xu, Zhang, Zengjin, Meng, Qingshun, Zhou, Jun, Li, Dawei, Zhang, Jingjing, Ni, Peixiang, Li, Songgang, Ran, Longhua, Li, Heng, Zhang, Jianguo, Li, Ruiqiang, Li, Shengting, Zheng, Hongkun, Lin, Wei, Li, Guangyuan, Wang, Xiaoling, Zhao, Wenming, Li, Jun, Ye, Chen, Dai, Mingtao, Ruan, Jue, Zhou, Yan, Li, Yuanzhe, He, Ximiao, Zhang, Yunze, Wang, Jing, Huang, Xiangang, Tong, Wei, Chen, Jie, Ye, Jia, Chen, Chen, Wei, Ning, Li, Guoqing, Dong, Le, Lan, Fengdi, Sun, Yongqiao, Zhang, Zhenpeng, Yang, Zheng, Yu, Yingpu, Huang, Yanqing, He, Dandan, Xi, Yan, Wei, Dong, Qi, Qiuhui, Li, Wenjie, Shi, Jianping, Wang, Miaoheng, Xie, Fei, Wang, Jianjun, Zhang, Xiaowei, Wang, Pei, Zhao, Yiqiang, Li, Ning, Yang, Ning, Dong, Wei, Hu, Songnian, Zeng, Changqing, Zheng, Weimou, Hao, Bailin, Hillier, Ladeana W, Yang, Shiaw-Pyng, Warren, Wesley C, Wilson, Richard K, Brandström, Mikael, Ellegren, Hans, Crooijmans, Richard P M A, van der Poel, Jan J, Bovenhuis, Henk, Groenen, Martien A M, Ovcharenko, Ivan, Gordon, Laurie, Stubbs, Lisa, Lucas, Susan, Glavina, Tijana, Aerts, Andrea, Kaiser, Pete, Rothwell, Lisa, Young, John R, Rogers, Sally, Walker, Brian A, van Hateren, Andy, Kaufman, Jim, Bumstead, Nat, Lamont, Susan J, Zhou, Huaijun, Hocking, Paul M, Morrice, David, de Koning, Dirk-Jan, Law, Andy, Bartley, Neil, Burt, David W, Hunt, Henry, Cheng, Hans H, Gunnarsson, Ulrika, Wahlberg, Per, Andersson, Leif, Kindlund, Ellen, Tammi, Martti T, Andersson, Björn, Webber, Caleb, Ponting, Chris P, Overton, Ian M, Boardman, Paul E, Tang, Haizhou, Hubbard, Simon J, Wilson, Stuart A, Yu, Jun, Wang, Jian, Yang, Huanming, Wong, Gane Ka-Shu, Liu, Bin, Wang, Jun, Zhang, Yong, Yang, Xu, Zhang, Zengjin, Meng, Qingshun, Zhou, Jun, Li, Dawei, Zhang, Jingjing, Ni, Peixiang, Li, Songgang, Ran, Longhua, Li, Heng, Zhang, Jianguo, Li, Ruiqiang, Li, Shengting, Zheng, Hongkun, Lin, Wei, Li, Guangyuan, Wang, Xiaoling, Zhao, Wenming, Li, Jun, Ye, Chen, Dai, Mingtao, Ruan, Jue, Zhou, Yan, Li, Yuanzhe, He, Ximiao, Zhang, Yunze, Wang, Jing, Huang, Xiangang, Tong, Wei, Chen, Jie, Ye, Jia, Chen, Chen, Wei, Ning, Li, Guoqing, Dong, Le, Lan, Fengdi, Sun, Yongqiao, Zhang, Zhenpeng, Yang, Zheng, Yu, Yingpu, Huang, Yanqing, He, Dandan, Xi, Yan, Wei, Dong, Qi, Qiuhui, Li, Wenjie, Shi, Jianping, Wang, Miaoheng, Xie, Fei, Wang, Jianjun, Zhang, Xiaowei, Wang, Pei, Zhao, Yiqiang, Li, Ning, Yang, Ning, Dong, Wei, Hu, Songnian, Zeng, Changqing, Zheng, Weimou, Hao, Bailin, Hillier, Ladeana W, Yang, Shiaw-Pyng, Warren, Wesley C, Wilson, Richard K, Brandström, Mikael, Ellegren, Hans, Crooijmans, Richard P M A, van der Poel, Jan J, Bovenhuis, Henk, Groenen, Martien A M, Ovcharenko, Ivan, Gordon, Laurie, Stubbs, Lisa, Lucas, Susan, Glavina, Tijana, Aerts, Andrea, Kaiser, Pete, Rothwell, Lisa, Young, John R, Rogers, Sally, Walker, Brian A, van Hateren, Andy, Kaufman, Jim, Bumstead, Nat, Lamont, Susan J, Zhou, Huaijun, Hocking, Paul M, Morrice, David, de Koning, Dirk-Jan, Law, Andy, Bartley, Neil, Burt, David W, Hunt, Henry, Cheng, Hans H, Gunnarsson, Ulrika, Wahlberg, Per, Andersson, Leif, Kindlund, Ellen, Tammi, Martti T, Andersson, Björn, Webber, Caleb, Ponting, Chris P, Overton, Ian M, Boardman, Paul E, Tang, Haizhou, Hubbard, Simon J, Wilson, Stuart A, Yu, Jun, Wang, Jian, and Yang, Huanming

Published
2004

27. The Genomes of Oryza sativa: A History of Duplications

Author

Yu, Jun, primary, Wang, Jun, additional, Lin, Wei, additional, Li, Songgang, additional, Li, Heng, additional, Zhou, Jun, additional, Ni, Peixiang, additional, Dong, Wei, additional, Hu, Songnian, additional, Zeng, Changqing, additional, Zhang, Jianguo, additional, Zhang, Yong, additional, Li, Ruiqiang, additional, Xu, Zuyuan, additional, Li, Shengting, additional, Li, Xianran, additional, Zheng, Hongkun, additional, Cong, Lijuan, additional, Lin, Liang, additional, Yin, Jianning, additional, Geng, Jianing, additional, Li, Guangyuan, additional, Shi, Jianping, additional, Liu, Juan, additional, Lv, Hong, additional, Li, Jun, additional, Wang, Jing, additional, Deng, Yajun, additional, Ran, Longhua, additional, Shi, Xiaoli, additional, Wang, Xiyin, additional, Wu, Qingfa, additional, Li, Changfeng, additional, Ren, Xiaoyu, additional, Wang, Jingqiang, additional, Wang, Xiaoling, additional, Li, Dawei, additional, Liu, Dongyuan, additional, Zhang, Xiaowei, additional, Ji, Zhendong, additional, Zhao, Wenming, additional, Sun, Yongqiao, additional, Zhang, Zhenpeng, additional, Bao, Jingyue, additional, Han, Yujun, additional, Dong, Lingli, additional, Ji, Jia, additional, Chen, Peng, additional, Wu, Shuming, additional, Liu, Jinsong, additional, Xiao, Ying, additional, Bu, Dongbo, additional, Tan, Jianlong, additional, Yang, Li, additional, Ye, Chen, additional, Zhang, Jingfen, additional, Xu, Jingyi, additional, Zhou, Yan, additional, Yu, Yingpu, additional, Zhang, Bing, additional, Zhuang, Shulin, additional, Wei, Haibin, additional, Liu, Bin, additional, Lei, Meng, additional, Yu, Hong, additional, Li, Yuanzhe, additional, Xu, Hao, additional, Wei, Shulin, additional, He, Ximiao, additional, Fang, Lijun, additional, Zhang, Zengjin, additional, Zhang, Yunze, additional, Huang, Xiangang, additional, Su, Zhixi, additional, Tong, Wei, additional, Li, Jinhong, additional, Tong, Zongzhong, additional, Li, Shuangli, additional, Ye, Jia, additional, Wang, Lishun, additional, Fang, Lin, additional, Lei, Tingting, additional, Chen, Chen, additional, Chen, Huan, additional, Xu, Zhao, additional, Li, Haihong, additional, Huang, Haiyan, additional, Zhang, Feng, additional, Xu, Huayong, additional, Li, Na, additional, Zhao, Caifeng, additional, Li, Shuting, additional, Dong, Lijun, additional, Huang, Yanqing, additional, Li, Long, additional, Xi, Yan, additional, Qi, Qiuhui, additional, Li, Wenjie, additional, Zhang, Bo, additional, Hu, Wei, additional, Zhang, Yanling, additional, Tian, Xiangjun, additional, Jiao, Yongzhi, additional, Liang, Xiaohu, additional, Jin, Jiao, additional, Gao, Lei, additional, Zheng, Weimou, additional, Hao, Bailin, additional, Liu, Siqi, additional, Wang, Wen, additional, Yuan, Longping, additional, Cao, Mengliang, additional, McDermott, Jason, additional, Samudrala, Ram, additional, Wang, Jian, additional, Wong, Gane Ka-Shu, additional, and Yang, Huanming, additional

Published
2005
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28. Factor requirements for translation initiation on the Simian picornavirus internal ribosomal entry site.

Author

de Breyne, Sylvain, Yu, Yingpu, Pestova, Tatyana V, and Hellen, Christopher U T

Abstract

The Simian picornavirus type 9 (SPV9) 5'-untranslated region (5' UTR) has been predicted to contain an internal ribosomal entry site (IRES) with structural elements that resemble domains of hepacivirus/pestivirus (HP) IRESs. In vitro reconstitution of initiation confirmed that this 5' UTR contains an IRES and revealed that it has both functional similarities and differences compared to HP IRESs. Like HP IRESs, the SPV9 IRES bound directly to 40S subunits and eukaryotic initiation factor (eIF) 3, depended on the conserved domain IIId for ribosomal binding and consequently for function, and additionally required eIF2/initiator tRNA to yield 48S complexes that formed elongation-competent 80S ribosomes in the presence of eIF5, eIF5B, and 60S subunits. Toeprinting analysis revealed that eIF1A stabilized 48S complexes, whereas eIF1 induced conformational changes in the 40S subunit, likely corresponding to partial opening of the entry latch of the mRNA-binding channel, that were exacerbated by eIF3 and suppressed by eIF1A. The SPV9 IRES differed from HP IRESs in that its function was enhanced by eIF4A/eIF4F when the IRES was adjacent to the wild-type coding sequence, but was less affected by these factors or by a dominant negative eIF4A mutant when potentially less structured coding sequences were present. Exceptionally, this IRES promoted binding of initiator tRNA to the initiation codon in the P site of 40S subunits independently of eIF2. Although these 40S/IRES/tRNA complexes could not form active 80S ribosomes, this constitutes a second difference between the SPV9 and HP IRESs. eIF1 destabilized the eIF2-independent ribosomal binding of initiator tRNA.

Published
2008
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29. miRNA independent hepacivirus variants suggest a strong evolutionary pressure to maintain miR-122 dependence

Author

Yu, Yingpu, Scheel, Troels K. H., Luna, Joseph M., Chung, Hachung, Nishiuchi, Eiko, Scull, Margaret A., Echeverria, Natalia, Ricardo-Lax, Inna, Kapoor, Amit, Lipkin, W. Ian, Divers, Thomas J., Antczak, Douglas F., Tennant, Bud C., and Rice, Charles M.

Subjects
Hepatitis C virus, Tropisms, Immunity, MicroRNA, 3. Good health
Abstract

Hepatitis C virus (HCV) requires the liver specific micro-RNA (miRNA), miR-122, to replicate. This was considered unique among RNA viruses until recent discoveries of HCV-related hepaciviruses prompting the question of a more general miR-122 dependence. Among hepaciviruses, the closest known HCV relative is the equine non-primate hepacivirus (NPHV). Here, we used Argonaute cross-linking immunoprecipitation (AGO-CLIP) to confirm AGO binding to the single predicted miR-122 site in the NPHV 5’UTR in vivo. To study miR-122 requirements in the absence of NPHV-permissive cell culture systems, we generated infectious NPHV/HCV chimeric viruses with the 5’ end of NPHV replacing orthologous HCV sequences. These chimeras were viable even in cells lacking miR-122, although miR-122 presence enhanced virus production. No other miRNAs bound this region. By random mutagenesis, we isolated HCV variants partially dependent on miR-122 as well as robustly replicating NPHV/HCV variants completely independent of any miRNAs. These miRNA independent variants even replicate and produce infectious particles in non-hepatic cells after exogenous delivery of apolipoprotein E (ApoE). Our findings suggest that miR-122 independent HCV and NPHV variants have arisen and been sampled during evolution, yet miR-122 dependence has prevailed. We propose that hepaciviruses may use this mechanism to guarantee liver tropism and exploit the tolerogenic liver environment to avoid clearance and promote chronicity.

30. A genetic variation map for chicken with 2.8 million single-nucleotide polymorphisms.

Author

Wong GK, Liu B, Wang J, Zhang Y, Yang X, Zhang Z, Meng Q, Zhou J, Li D, Zhang J, Ni P, Li S, Ran L, Li H, Zhang J, Li R, Li S, Zheng H, Lin W, Li G, Wang X, Zhao W, Li J, Ye C, Dai M, Ruan J, Zhou Y, Li Y, He X, Zhang Y, Wang J, Huang X, Tong W, Chen J, Ye J, Chen C, Wei N, Li G, Dong L, Lan F, Sun Y, Zhang Z, Yang Z, Yu Y, Huang Y, He D, Xi Y, Wei D, Qi Q, Li W, Shi J, Wang M, Xie F, Wang J, Zhang X, Wang P, Zhao Y, Li N, Yang N, Dong W, Hu S, Zeng C, Zheng W, Hao B, Hillier LW, Yang SP, Warren WC, Wilson RK, Brandström M, Ellegren H, Crooijmans RP, van der Poel JJ, Bovenhuis H, Groenen MA, Ovcharenko I, Gordon L, Stubbs L, Lucas S, Glavina T, Aerts A, Kaiser P, Rothwell L, Young JR, Rogers S, Walker BA, van Hateren A, Kaufman J, Bumstead N, Lamont SJ, Zhou H, Hocking PM, Morrice D, de Koning DJ, Law A, Bartley N, Burt DW, Hunt H, Cheng HH, Gunnarsson U, Wahlberg P, Andersson L, Kindlund E, Tammi MT, Andersson B, Webber C, Ponting CP, Overton IM, Boardman PE, Tang H, Hubbard SJ, Wilson SA, Yu J, Wang J, and Yang H

Subjects
Alleles, Amino Acid Sequence, Animals, Animals, Domestic classification, Animals, Domestic genetics, Chickens classification, Chromosomes genetics, Female, Haplotypes genetics, Humans, Molecular Sequence Data, Ornithine Carbamoyltransferase chemistry, Selection, Genetic, Chickens genetics, Genome, Genomics, Physical Chromosome Mapping, Polymorphism, Single Nucleotide genetics
Abstract

We describe a genetic variation map for the chicken genome containing 2.8 million single-nucleotide polymorphisms (SNPs). This map is based on a comparison of the sequences of three domestic chicken breeds (a broiler, a layer and a Chinese silkie) with that of their wild ancestor, red jungle fowl. Subsequent experiments indicate that at least 90% of the variant sites are true SNPs, and at least 70% are common SNPs that segregate in many domestic breeds. Mean nucleotide diversity is about five SNPs per kilobase for almost every possible comparison between red jungle fowl and domestic lines, between two different domestic lines, and within domestic lines--in contrast to the notion that domestic animals are highly inbred relative to their wild ancestors. In fact, most of the SNPs originated before domestication, and there is little evidence of selective sweeps for adaptive alleles on length scales greater than 100 kilobases.

Published
2004
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31. Severe acute respiratory syndrome-associated coronavirus genotype and its characterization.

Author

Li L, Wang Z, Lu Y, Bao Q, Chen S, Wu N, Cheng S, Weng J, Zhang Y, Yan J, Mei L, Wang X, Zhu H, Yu Y, Zhang M, Li M, Yao J, Lu Q, Yao P, Bo X, Wo J, Wang S, and Hu S

Subjects
Humans, Middle Aged, Mutation, Genotype, Severe acute respiratory syndrome-related coronavirus genetics
Abstract

Objective: To study the severe acute respiratory syndrome (SARS)-associated coronavirus genotype and its characteristics., Methods: A SARS-associated coronavirus isolate named ZJ01 was obtained from throat swab samples taken from a patient in Hangzhou, Zhejing province. The complete genome sequence of ZJ01 consisted of 29,715 bp (GenBank accession: AY297028, version: gi: 30910859). Seventeen SARS-associated coronavirus genome sequences in GenBank were compared to analyze the common sequence variations and the probability of co-occurrence of multiple polymorphisms or mutations. Phylogenetic analysis of those sequences was done., Results: By bioinformatics processing and analysis, the 5 loci nucleotides at ZJ01 genome were found being T, T, G, T and T, respectively. Compared with other SARS-associated coronavirus genomes in the GenBank database, an A/G mutation was detected besides the other 4 mutation loci (C:G:C:C/T:T:T:T) involved in this genetic signature. Therefore a new definition was put forward according to the 5 mutation loci. SARS-associated coronavirus strains would be grouped into two genotypes (C:G:A:C:C/T:T:G:T:T), and abbreviated as SARS coronavirus C genotype and T genotype. On the basis of this new definition, the ZJ01 isolate belongs to SARS-associated coronavirus T genotype, first discovered and reported in mainland China. Phylogenetic analysis of the spike protein gene fragments of these SARS-associated coronavirus strains showed that the GZ01 isolate was phylogenetically distinct from other isolates, and compared with groups F1 and F2 of the T genotype, the isolates of BJ01 and CUHK-W1 were more closely related to the GZ01 isolate. It was interesting to find that two (A/G and C/T) of the five mutation loci occurred in the spike protein gene, which caused changes of Asp to Gly and Thr to Ile in the protein, respectively., Conclusion: Attention should be paid to whether these genotype and mutation patterns are related to the virus's biological activities,epidemic characteristics and host clinical symptoms.

Published
2003

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