       Document 0970
 DOCN  M9540970
 TI    RNA virus quasispecies: significance for viral disease and epidemiology.
 DT    9504
 AU    Duarte EA; Novella IS; Weaver SC; Domingo E; Wain-Hobson S; Clarke DK;
       Moya A; Elena SF; de la Torre JC; Holland JJ; Department of Biology,
       University of California San Diego,; LaJolla 92093-0116.
 SO    Infect Agents Dis. 1994 Aug;3(4):201-14. Unique Identifier : AIDSLINE
       MED/95128557
 AB    The experimental evidence available for animal and plant RNA viruses, as
       well as other RNA genetic elements (viroids, satellites, retroelements,
       etc.), reinforces the view that many different types of genetic
       alterations may occur during RNA genome replication. This is
       fundamentally because of infidelity of genome replication and large
       population sizes. Homologous and heterologous recombination, as well as
       gene reassortments occur frequently during replication of retroviruses
       and most riboviruses, especially those that use enzymes with limited
       processivity. Following the generation of variant genomes, selection,
       which is dependent on environmental parameters in ways that are poorly
       understood, sorts out those genome fits enough to generate viable
       quasispecies. Chance events can also be destabilizing, as illustrated by
       recent results on fitness loss and other phenotypic changes accompanying
       bottleneck transmission. Variation, selection, and random sampling of
       genomes occur continuously and unavoidably during virus evolution.
       Evolution of RNA viruses is largely unpredictable because of the
       stochastic nature of mutation and recombination events, as well as the
       subtle effects of chance transmission events and host/environmental
       factors. Among environmental factors, alterations resulting from human
       intervention (deforestation, agricultural activities, global climatic
       changes, etc.) may alter dispersal patterns and provide new adaptive
       possibilities to viral quasispecies. Current understanding of RNA virus
       evolution suggests several strategies to control and diagnose viral
       diseases. The new generation of chemically defined vaccines and
       diagnostic reagents (monoclonal antibodies, peptide antigens,
       oligonucleotides for polymerase chain reaction amplification, etc.) may
       be adequate to prevent disease and detect some or even most of the
       circulating quasispecies of any given RNA pathogen. However, the
       dynamics of viral quasispecies mandate careful consideration of those
       reagents to be incorporated into diagnostic kits. Broadening diagnosis
       without jeopardizing specificity of detection will be challenging. There
       is a finite probability (impossible to quantify at present) that a
       defined vaccine may promote selection of escape mutants or a particular
       diagnostic kit may fail to detect a viral pathogen. Of particular
       concern are the potential long-term effects of weak selective pressures
       that may initially go unnoticed. Variant viruses resulting from
       evolutionary pressure imposed by vaccines or drugs may insidiously and
       gradually replace previous quasispecies. The great potential for
       variation and phenotypic diversity of some important RNA virus pathogens
       (human immunodeficiency virus, the hepatitis viruses, the newly
       recognized human hantaviruses, etc.) has become clear. Prevention and
       therapy should rely on multicomponent vaccines and antiviral agents to
       address the complexity of RNA quasispecies mutant spectra.(ABSTRACT
       TRUNCATED AT 400 WORDS)
 DE    Evolution  *RNA Viruses/GENETICS/PATHOGENICITY  Support, Non-U.S. Gov't
       Support, U.S. Gov't, P.H.S.  Viral Vaccines  Virus Diseases/PREVENTION &
       CONTROL/*VIROLOGY  Virus Replication  JOURNAL ARTICLE  REVIEW  REVIEW,
       TUTORIAL

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).

