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Progress in Drug Research / Fortschritte der Arzneimittelforschung / Progrès des recherches pharmaceutiques pp 99–128Cite as

Birkhäuser

Viral quasispecies and the problem of vaccine-escape and drug-resistant mutants

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Abstract

Since a first version of this article on the relevance of quasispecies to viral disease control was published by one of us [1], an explosion of information on viral quasispecies has been gathered by several groups. For many viruses, extreme complexity at the population level has been documented by direct copying into cDNA of viral RNA extracted from biological specimens using reverse transcriptase and amplification by thermostable polymerases (RT-PCR).Two systems relevant to human health for which extensive population heterogeneity has been revealed are hepatitis C virus (HCV) [2-4] and the human immunodeficiency viruses (HIV) [5-7, and references therein]. Particularly dramatic has been the inability to produce effective vaccines against any of these viruses [8-11] in spite of an urgent need to stop the progression of the AIDS pandemic. Also, the systematic selection of HIV-1 mutants resistant to antiretroviral inhibitors [12-14] has greatly limited the efficacy of antiretroviral treatments until the recent encouraging results with combination therapy.

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Abbreviations

3TC:

(-)-3’-thia-2’-deoxycytidine

∝-APA:

∝-anilinophenylacetamide

AIDS:

acquired immune difficiency syndrome

AZT:

3’-2’,3’-dideoxythymidine

BHAP:

bis(heteroaryl)piperazine

d4T:

3’-2’,3’-didehydro-3’-2’,3’-dideoxythymidine

ddC:

3’-2’,3’-dideoxycytimidine

ddI:

3’-2’,3’-dideoxyinosine

FMDV:

foot-and-mouth disease virus

HBV:

hepatitis B virus

HCV:

hepatitis C virus

HEPT:

1-(2-hydroxyethoxymethyl)-6-(phenylthio)thymine

HIV:

human immunodifficiency virus

HVR1:

hyperviable region 1

MAb:

monoclonal antibody

PETT:

N-(2-phenelthyl)-N’-(2-thiazolyl)thiourea

TIBO:

tetrahydroimidazo(4,5,1-jk)(1,4)benzodiapecin-2(1H)-one and -thione

VSV:

vesicular stomatitis virus

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  1. Centro de Biología Molecular «Severo Ochoa» (CSIC-UAM), Universidad Autónoma de Madrid Cantoblanco, 28049, Madrid, Spain

    Esteban Domingo, Luis Menéndez-Arias, Miguel E. QuiñonesMateu, Africa Holguín, Mónica Gutiérrez-Rivas & Miguel A. Martínez

  2. Recerca Medicina Interna, Hospital Vall d’Hebron, Pg. Vall d’Hebron, 119-129, Barcelona, Spain

    Josep Quer

  3. Department of Biology and Molecular Genetics, University of California, San Diego 9500, Gilman Drive, La Jolla, California, 92093-0116, USA

    Isabel S. Novella & John J. Holland

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Domingo, E. et al. (1997). Viral quasispecies and the problem of vaccine-escape and drug-resistant mutants. In: Jucker, E. (eds) Progress in Drug Research / Fortschritte der Arzneimittelforschung / Progrès des recherches pharmaceutiques. Progress in Drug Research / Fortschritte der Arzneimittelforschung / Progrès des recherches pharmaceutiques, vol 48. Birkhäuser, Basel. https://doi.org/10.1007/978-3-0348-8861-5_4

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