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Viral evolution and adaption

Viral evolution and adaption . BTY328: Virology wstafford@uwc.ac.za. Evolving viruses and emerging diseases. Viruses reproduce in minutes Constant mutation and recombination Constant migration Constant adaptation. To combat emerging diseases we require: Surveillance and Testing

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Viral evolution and adaption

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  1. Viral evolution and adaption BTY328: Virology wstafford@uwc.ac.za

  2. Evolving viruses and emerging diseases Viruses reproduce in minutes • Constant mutation and recombination • Constant migration • Constant adaptation To combat emerging diseases we require: • Surveillance and Testing • New strategies to limit the spread of the virus, reduce its virulence together with improving host defence and treatment strategies‏

  3. Evolving viruses and emerging diseases Reproduce in minutes • Constant mutation and recombination • Constant migration • Constant adaptation to host and environment To combat emerging diseases we require: • Surveillance and testing • New strategies to limit the spread of the virus, reduce its virulence, improve host defence and treatment strategies‏.

  4. Why is viral evolution and adaption relevant today? • Genetic and biologic flexibility of microbes responding to changes in the environment (anthropogenic)‏ • Human behavior and activities such as travel enable viruses to spread rapidly to new hosts • Global public health measures are required to combat pandemics • The new threats of biowarefare/bioterrorism

  5. Sequence variation during virus replication • Intrinsic error rates of polymerases: DNA polymerase has proof-reading capability; intrinsic error rate ~ 10-6 to 10-5 RNA polymerase has no proof-reading capability; intrinsic error rate ~ 10-3 to 10-4 • Error rates may be different in different genome regions, e.g., “hotspots” • Homologous or non-homologous recombination may occur in RNA or DNA viruses to yield new variants

  6. Sequence variation and virus evolution • Replication errors include mutations: substitution, single base change as well as deletions. • Intragenomic gene duplication • Intergenomic recombination • gene duplication • acquisition of additional genes • sequence substitutions, chimaerogenesis • Virus evolution may be accelerated by co-infection

  7. Intrinsic mutation rates among RNA viruses vary From Drake & Holland, 1999, PNAS 96:13909

  8. Mechanisms of recombination of viral RNAs Left: Generalized viral RNA recombination. Bottom: Three classes of intergenomic RNA recombination: 1) Requiring substantial base pairing but no identifiable RNA secondary structures or regulatory elements; 2) Occurring in association with identifiable RNA ,structures or regulatory elements, but not requiring substantial base pairing; 3) A combination of 1 and 2. From your text: Flint et al., 2004

  9. Quasi-species • Due to this sequence variation, many variants are found in a virus population; the “quasi-species cloud” is the mutant spectrum derived from the dominant master copy • A genetic bottleneck occurs when a virus population is constrained, resulting in loss of diversity • A small founder population coming through a genetic bottleneck may give rise to a divergent, adapted population

  10. Viral quasispecies, population size, bottlenecks, and fitness

  11. General Interactions of Hosts and Viruses Emerging viruses & severe pathogens

  12. HIV and SIV Phylogeny ZR59: the earliest known HIV sample

  13. HIV-1 subtype and recombinant prevalence in the world

  14. Evolution of HIV • HIV viruses evolved by mutation & recombination • Mutation rate is between 10-5 and 10-4 • > 109 new cells infected every day • every possible single-point mutation occurs between 104 and 105 times per day in infected persons • Over a 10 year clinical latency period, the virus has gone through more than 3000 generations • HIV transmitted from infected person to an uninfected person is thousands of generations removed from the virus causing the initial infection

  15. HIV variation within the host Early HIV-1 infection is characterized by a near homogenous viral population. The extensive heterogeneity seen in HIV-1 during disease progression is due to: • Rapid viral turn over‏ • High rate of incorrect nucleotide substitution during reverse transcription • High rate of recombination among the different HIV-1 strains This ability to generate genetic diversity allows the virus to escape host immune responses and also to develop resistance to ARVs.

  16. Origin and spread of Smallpox? • The population in the Fertile Crescent about 5000 years ago could be larger enough. The original source may be the animal viruses. • The rindpest virus of cattle is the closet relative of measles virus. And cattle were domesticated in Fertile Crescent about 5-10 thousand years ago. • A zoonosis from cattle to humans?

  17. Emergence of smallpox epidemics • The earliest physical evidence : the pustular rash on the mummified body of Pharaoh Ramesses V of Egypt, who died in 1157 BC. • Traders carried the disease from Egypt to India during the 1st millennium BC. • From there it swept into China in the 1st century AD and reached Japan in the 6th century. • Returning crusaders provided a way for smallpox to spread through Europe in the 11th and 12th centuries. • The Spanish inadvertently owe much of their success in conquering the Aztecs and Incas in Mexico in the 16th century to smallpox.

  18. Influenza origin and spread • Three major groups of influenza • Influenza C • Influenza B • Influenza A • Subdivided into several subtypes (H5N1, …)‏ • Infect not only humans but also animals • Mutate and evolve rapidly

  19. Type A Influenza • 16 different hemagglutinin antigens (HA) and nine different neuraminidase (NA) antigens • Human disease historically been caused by three subtypes of HA (H1, H2, H3) and two subtypes of NA (N1 and N2)‏ • All known subtypes of influenza A can be found in birds, but only subtypes H5 and H7 have caused severe outbreaks of disease in birds

  20. Influenza A viruses Comparison of 41 influenza A virus NP genes rooted to B virus NP (Left) DNA phylogenetic tree. (Right) amino acid phylogenetic tree. Blue- five host specific lineages. Pink- viruses that have been transmitted to other hosts

  21. Evolution of the Influenza virus • The virus is in constant evolution • Two types of evolution • Antigenic Drift: • Small errors in transcription that are not corrected • Antigenic Shift • Mutations • Recombination

  22. Some Believe Another Massive Flu Pandemic is Conceivable The emergence of a strain of flu, unresponsive to existing vaccines Fast, hidden proliferation due to travel 1950 – 200 million travelers 2004 – 1.4 billion travelers

  23. The success in viral evolution: finding a new host How does a new viral population find their way into the hosts? How does a existing viral population find their way into new hosts?

  24. Successful evolution? “It is not the strongest of the species that survives, nor the most intelligent, but the one most responsive to change.” Charles Darwin

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