Document 0027
 DOCN  M95A0027
 TI    Genetic heterogeneity of hepatitis C virus: quasispecies and genotypes.
 DT    9510
 AU    Bukh J; Miller RH; Purcell RH; Hepatitis Viruses Section, National
       Institutes of Health,; Bethesda, Maryland 20892-0740, USA.
 SO    Semin Liver Dis. 1995 Feb;15(1):41-63. Unique Identifier : AIDSLINE
       MED/95320599
 AB    Worldwide, HCV is a major etiologic agent of chronic hepatitis that may
       lead to the development of liver cirrhosis and hepatocellular carcinoma.
       Thus, significant morbidity and mortality is caused by HCV infection and
       effective control measures against the spread of this virus are needed.
       Originally, the extent of genetic heterogeneity of HCV was not fully
       appreciated. However, the breadth of the genetic heterogeneity of HCV is
       great, and this may have important implications in diagnosis,
       pathogenesis, treatment, and vaccine development. In an infected
       individual the HCV genome population circulates as a quasispecies
       distribution of closely related yet heterogeneous RNA sequences centered
       around one dominant sequence. The dominant sequence, as well as the
       consensus sequence, changes sequentially during the course of the
       infection. A hypervariable region (HVR1) within one of the envelope
       proteins of HCV (E2) evolves very rapidly. Patients infected with HCV
       mount a humoral immune response to epitopes of HVR1. However, sequential
       changes in the consensus sequence of HVR1 during infection result in the
       generation of variants that are not recognized by preexisting
       antibodies. This might represent a mechanism by which HCV evades host
       immune surveillance and establishes and maintains persistent infection.
       It will be important to determine whether HVR1 of HCV, as was found for
       the V3 loop of HIV, contains epitopes that elicit neutralizing
       antibodies against HCV. Furthermore, it will be important to determine
       whether the quasispecies nature of HCV helps the virus evade the
       cytotoxic T-cell response of the host. Analysis of complete or partial
       HCV genomic sequences revealed that HCV exists as multiple, distinct
       genotypes. A total of nine major genetic groups and at least 30
       subgroups have been recognized. To evaluate the current classification
       of HCV genotypes, we performed phylogenetic analyses of complete and
       partial nucleotide sequences from isolates that represent all published
       variants of HCV. Analysis of complete HCV sequences, which represent
       three major genetic groups, supports the currently used genotype
       classification scheme. However, analysis of the partial genomic regions
       (ie, C, E1, and NS5b) of HCV isolates that represent all recognized
       variants of HCV demonstrates that the genetic relatedness among some of
       the genotypes was not equivalent in the different gene regions.
       Furthermore, the distinction among isolates, subtypes, and types of HCV
       was not always clear. This finding might reflect the shortcomings of
       analyzing only limited gene regions or may reflect the wide spectrum of
       genetic variation of HCV.(ABSTRACT TRUNCATED AT 400 WORDS)
 DE    Animal  Genotype  Hepatitis C
       Viruses/CLASSIFICATION/*GENETICS/IMMUNOLOGY  Human  Phylogeny  Viral
       Hepatitis Vaccines  JOURNAL ARTICLE  REVIEW  REVIEW, ACADEMIC

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