Virus Evolution Molecular Epidemiology of Viral Infections Jen-Ren Wang,Ph.D. 王貞仁 Dept.of Medical Laboratory Science and Biotechnology National Cheng Kung University
Virus Evolution Molecular Epidemiology of Viral Infections Jen-Ren Wang, Ph. D. 王貞仁 Dept. of Medical Laboratory Science and Biotechnology National Cheng Kung University
Virus evolution Virus evolution constant change of a viral population in the face of selection pressures Virus populations display diversity. The sources of diversity mutation (genetic drift),recombination,natural selection (adaptation,fitness)
Virus evolution • Virus evolution：constant change of a viral population in the face of selection pressures • Virus populations display diversity. • The sources of diversity：mutation (genetic drift), recombination, natural selection (adaptation, fitness)
Replicating viruses produce large numbers of mutant genomes RNA virus Error rate-1 in 104 or 105 DNA virus lower error rate-1 in 107 or 108 error-correcting DNA polymerase latent infection
Replicating viruses produce large numbers of mutant genomes • RNA virus：Error rate- 1 in 104 or 105 • DNA virus：lower error rate – 1 in 107 or 108 - error-correcting DNA polymerase - latent infection
RNA viruses and quasispecies Viruses exist as dynamic distributions of non identical but related replicons. ·Polymorphism
RNA viruses and quasispecies • Viruses exist as dynamic distributions of non identical but related replicons. • Polymorphism
Viruses exchange information ·Recombination polymerase changes templates (copy choice)during replication(RNA virus) nucleic acid segments are broken and rejoined (DNA virus) ·Reassortment
Viruses exchange information • Recombination - polymerase changes templates (copy choice) during replication (RNA virus) - nucleic acid segments are broken and rejoined (DNA virus) • Reassortment
Molecular studies are useful in Epidemiological investigation Real-time surveillance Make predictions about future developments
Molecular studies are useful in • Epidemiological investigation • Real-time surveillance • Make predictions about future developments
Molecular epidemiology of viral infections Distinguish between related strains of viruses Deduce the relationships between viruses from different outbreaks or individual patients Dissemination and evolution of viruses can be followed locally and globally
Molecular epidemiology of viral infections • Distinguish between related strains of viruses • Deduce the relationships between viruses from different outbreaks or individual patients • Dissemination and evolution of viruses can be followed locally and globally
Molecular epidemiology of viruses Determine the sources of imported viruses Monitor pathways of virus transmission Monitor the process of control activities Develop molecular reagents for rapid detection of viral infections
Molecular epidemiology of viruses • Determine the sources of imported viruses • Monitor pathways of virus transmission • Monitor the process of control activities • Develop molecular reagents for rapid detection of viral infections
Implications of sequence information Maintain effective diagnostics,treatment,and prophylaxis Strain-specific treatment:HIV,HCV,HBV,CMV HCV indicator of susceptibility to specific treatments eg.Genotype 1 is resistant to interferon therapy Detection of mutation that confer antiviral resistance -HIV monitor emergence of drug resistance Distinguish between more or less pathogenic strains Avian influenza HAPI or LAPI -HCV differ in the in tendency to cause liver damage Attenuated vaccine strains
Implications of sequence information • Maintain effective diagnostics, treatment, and prophylaxis – Strain-specific treatment: HIV, HCV, HBV, CMV – HCV：indicator of susceptibility to specific treatments eg. Genotype 1 is resistant to interferon therapy – Detection of mutation that confer antiviral resistance – HIV：monitor emergence of drug resistance • Distinguish between more or less pathogenic strains – Avian influenza ：HAPI or LAPI – HCV：differ in the in tendency to cause liver damage – Attenuated vaccine strains
Methods for molecular epidemiological analysis Oligonucleotide fingerprinting:Rnase T1 Recognize relationship between isolates separate from ancestral infection by no more than 3 to 5 years Monoclonal antibody characterization of viral epitopes Nucleic acid analysis Nucleic acid hybridization PCR-RFLP PCR-SSCP PCR-sequencing
Methods for molecular epidemiological analysis • Oligonucleotide fingerprinting: Rnase T1 Recognize relationship between isolates separate from ancestral infection by no more than 3 to 5 years • Monoclonal antibody characterization of viral epitopes • Nucleic acid analysis Nucleic acid hybridization PCR-RFLP PCR-SSCP PCR-sequencing