1. Viral evolution and adaption
BTY328: Virology

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 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
Influenza C: mild disease
Influenza B: sporadic outbreaks of more severe respiratory disease
Influenza A: greatest concern

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

23. 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
(Title Appears) Today, some believe another massive flu pandemic is conceivable because of the (Text Box Appears) converging elements of a “perfect storm.” These elements include, first, (1st Bullet Appears) the possible emergence of a strain of influenza that is non-responsive to existing vaccines. Second, (2nd Bullet Appears) the association of the virus with a highly resistant secondary bacterial infection. And third, (3rd Bullet Appears) extraordinarily fast proliferation under the radar screen due to the hyper-mobility of today’s traveler’s. (1st Sub-Bullet Appears) Consider that in 1950 we had 200 million travelers worldwide. (2nd Sub-Bullet Appears) Fifty years later, this number has increased seven fold to 1.4 billion and continues to grow.7 (Quote Box Appears) Charles Darwin said, “It is not the strongest of the species that survives, nor the most intelligent, but the one most responsive to change.” To manage microbes we need to change faster than they do.

24. 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?

25. 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