Clinically relevant sequence-based genotyping of HBV, HCV, CMV, and HIV

The term 'genotyping' describes the genetic characterization of a genome. T he genotype analysis is performed to identify mutations that differentiate one individual or strain from another. The mutations may confer resistance to specific antiviral drugs or they may simply allow classification of a st rain as to 'type' and 'subtype'. There are four human viruses for which gen otype information is clinically useful. Hepatitis B virus (HBV) infections are being treated with antiretroviral drugs and resistance after prolonged treatment is common. Since HBV cannot be cultured, the only method of detec ting resistance-conferring mutations in the genome is a genotypic analysis. Hepatitis C virus (HCV) infection can be cured by treatment with the combi nation of interferon and ribavirin but certain strains of virus are more re sistant to treatment than others. The current recommendations are that all HCV type 1 infections be treated for 12 months whereas other types may be s uccessfully treated in 6 months. Since interferon treatment may have signif icant side effects, the determination of HCV genotype is an important aspec t of this therapeutic regimen. Treatment of cytomegalovirus (CMV) disease w ith nucleoside analogues occasionally results in resistant virus with mutat ions in the phosphotransferase gene (UL97) and/or the DNA polymerase gene ( UL54) that can be tested with phenotygic or genotypic assays. Since CMV gro ws very slowly, it may be more clinically useful to perform a rapid genotyp ic assay although only the UL97 gene can be efficiently genotyped. Finally, the virus for which genotyping has become the standard of care, human immu nodeficiency virus type I (HIV-I) can now be genotyped routinely by many cl inical virology labs experienced with molecular amplification methods and a utomated DNA sequencing technology. All currently-available antiretroviral drugs are directed against either the protease or reverse transcriptase gen es of HIV-1 and the mutations within these genes that confer resistance hav e been well described. Sequence-based genotyping methods are not necessaril y the best approach for routine genotyping of these four viruses, but seque ncing is the gold standard from which other methods are developed acid agai nst which they are compared. (C) 2001 Elsevier Science B.V. All rights rese rved.