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  • 1
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    Efficient initiation of HCV RNA replication in cell culture (2000)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2000-12-09
    Description: Hepatitis C virus (HCV) infection is a global health problem affecting an estimated 170 million individuals worldwide. We report the identification of multiple independent adaptive mutations that cluster in the HCV nonstructural protein NS5A and confer increased replicative ability in vitro. Among these adaptive mutations were a single amino acid substitution that allowed HCV RNA replication in 10% of transfected hepatoma cells and a deletion of 47 amino acids encompassing the interferon (IFN) sensitivity determining region (ISDR). Independent of the ISDR, IFN-alpha rapidly inhibited HCV RNA replication in vitro. This work establishes a robust, cell-based system for genetic and functional analyses of HCV replication.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Blight, K J -- Kolykhalov, A A -- Rice, C M -- AI40034/AI/NIAID NIH HHS/ -- CA57973/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 2000 Dec 8;290(5498):1972-4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Microbiology, Washington University School of Medicine, 660 South Euclid Avenue, St. Louis, MO 63110-1093, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11110665" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Substitution ; Hepacivirus/drug effects/genetics/*physiology ; Humans ; Interferon-alpha/pharmacology ; Mutation ; Phosphorylation ; Point Mutation ; RNA Replicase/genetics/metabolism ; RNA, Viral/*biosynthesis ; *Replicon ; Sequence Deletion ; Transfection ; Tumor Cells, Cultured ; Viral Nonstructural Proteins/*genetics/*metabolism ; Virus Replication
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
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  • 2
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    HCV persistence and immune evasion in the absence of memory T cell help (2003)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2003-10-25
    Description: Spontaneous resolution of hepatitis C virus (HCV) infection in humans usually affords long-term immunity to persistent viremia and associated liver diseases. Here, we report that memory CD4+ Tcells are essential for this protection. Antibody-mediated depletion of CD4+ Tcells before reinfection of two immune chimpanzees resulted in persistent, low-level viremia despite functional intra-hepatic memory CD8+ Tcell responses. Incomplete control of HCV replication by memory CD8+ Tcells in the absence of adequate CD4+ Tcell help was associated with emergence of viral escape mutations in class I major histocompatibility complex-restricted epitopes and failure to resolve HCV infection.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Grakoui, Arash -- Shoukry, Naglaa H -- Woollard, David J -- Han, Jin-Hwan -- Hanson, Holly L -- Ghrayeb, John -- Murthy, Krishna K -- Rice, Charles M -- Walker, Christopher M -- A14736/PHS HHS/ -- AI40034/AI/NIAID NIH HHS/ -- AI48231/AI/NIAID NIH HHS/ -- CA57973/CA/NCI NIH HHS/ -- CA85883/CA/NCI NIH HHS/ -- N01 HB27091/HB/NHLBI NIH HHS/ -- New York, N.Y. -- Science. 2003 Oct 24;302(5645):659-62.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Center for the Study of Hepatitis C, Rockefeller University, New York, NY 10021, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/14576438" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Amino Acid Substitution ; Animals ; Antigen Presentation ; Antigens, Viral/chemistry/genetics/immunology ; CD4-Positive T-Lymphocytes/*immunology ; CD8-Positive T-Lymphocytes/*immunology ; Epitopes ; Evolution, Molecular ; Hepacivirus/genetics/*immunology/*physiology ; Hepatitis C/*immunology/virology ; *Immunologic Memory ; Liver/immunology ; Major Histocompatibility Complex ; Molecular Sequence Data ; Mutation ; Pan troglodytes ; T-Lymphocyte Subsets/immunology ; Time Factors ; Viral Core Proteins/chemistry/genetics/immunology ; Viral Nonstructural Proteins/chemistry/genetics/immunology ; Viremia ; Virus Replication
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
    Location Call Number Expected Availability
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    PAPER CURRENT
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