HPV biology

151 known types of HPV. Most have no symptoms.

DNA virus, 3 genera. Genera is determined based on presence/absence of e5 gene. The high risk type has cancer risk rate of 97%. Type 16 & 18 cause cancer, and are blocked by the vaccine. Another vaccine blocks 4 serotypes. Including 6 & 11.

HPV and skin cancer?

10-15 % of cancers are caused by infection, usually a virus. HPV may cause skin cancer. HPV 5 & 8 are found in 90% of non melanoma skin cancers. But it is also common in the general population.

Zinc is a coactivator for many virus.

Molecular Clocks and the puzzle of RNA virus origins --Holmes 2003

Journal of Virology

Dr. Holmes investigates why phylogenetic dating of viral speciation implies that the major RNA virusus originated not more than 50,000 years ago, yet their hosts speciated many millions of years in the past.

One problem is the rate of replication, which is roughly 10^-3 subs/site/year (21), which further implies the average distance between any two sequences is limited to 500 years (since after 1000 years, every position will have mutated). Better to look at non-synonymous sites, assume the rate is 10^-5, and put the divergence at 50K years ago. Voiala.

So, do virus change their mutation rate? Is it because once adopted to their host species, they don't drift very much? No. Adoptation does not give RNA a repair mechanism, and mutation at synonymous sites doesn't slow down.

Perhaps different parts of the genome mutate at different speeds? Likely:

An important evolutionary by-product of these high mutation rates is a cap on genome size; genomes larger than ∼15 kb are rarely produced because of the “error threshold,” the generation of a prohibitive number of deleterious mutations (11). Since viral genome sizes are limited, sequence regions will encode multiple functions and individual mutations will often have pleiotropic effects, such as those influencing both cell tropism and immune evasion (1). This, in turn, may mean that there are relatively few evolutionary pathways that can be followed by RNA viruses; otherwise, at least one key function will be disrupted, so that mutations preferentially accumulate at that small proportion of sites that are free to vary. Supportive evidence for such a model is the frequency with which convergent evolution is observed for RNA viruses (4, 7, 13), as expected if only a limited number of evolutionary pathways are viable, and the evidence that RNA (37) and protein secondary structure (22) can act as constraints against sequence change.

Helpful to use a (skewed) gamma distribution to allow the rate to vary along the chromosone.

low α values (i.e., <1) mean that the sequence alignment is composed of both very quickly and very slowly evolving sites, and this appears to be true in most cases.

the three groups of flaviviruses, the mean d at these sites, corrected for multiple substitutions but without a gamma distribution, is ∼0.25 and is similar to the nonsynonymous distance estimated previously. The maximum likelihood estimate for the shape parameter of the gamma distribution for these data is highly skewed (α = 0.34). As expected, evolutionary distances increase if they are now estimated using this gamma model (mean d = 0.43), although not sufficiently to make a major difference to estimated divergence times, which only increase to a little over 20,000 years (again assuming a rate of 10−5 substitutions/site/year). However, more dramatic results are obtained if an even more skewed gamma distribution is used. If α = 0.1, then d increases to 2.3, so that maximum divergence times will be in the region of 100,000 years ago

Pox

Smallpox like all pox virus has its origin in African rodents. Camel pox is the closest extant variant.

Falciparum malaria was originally a bird parasite. see refs 12 &13.

Ar see also ref 21

Globalization, land use, and the invasion of the West Nile Virus (Kilpatrick, 2011)

Review article in Science, 21 October

WNV endemic in Africa, childhood disease (>80% of people over 15 having antibodies), considered nearly asymptotic & once even studied as an anti-cancer therapy.

WNV was first observed in the Americas in 1999, in New York City. In four years it was on the west coast, and after 10 years it had reached deep into South America. It had also (by 2002) changed 3 nucleotides/1 amino acid to increase transmission efficiency in C. pipiens and C. tarsalis mosquitos. In the US, 1.8 million people have been infected, 360,000 illnesses (20%), 12852 encephalitis (0.7%), and 1308 deaths (0.0007%). Big cost in blood donor screening. Given a US population of 250 million, these numbers do not seem alarming.

The disease is much worse in birds. Regional-scale population declines >50% have been reported in corvids, chickadees, titmice, wrens, and thrushes.

Robins (the bird, a species of thrush) are a preferred food source for mosquitos. The dominant WNV vectors are the mosquito species C. pipiens, C. restuans, and C. tarsalis. Some 30-80% of their feedings are on robins, though robins make up only 1-20% of the studied avian communities.

Robins do exceptionally well in human altered landscapes. Populations have doubled over the last 25 years (or is this because we stopped using DDT?? What were robin populations 100 years ago?)

WNV has chosen the "kill them fast" reproductive strategy. Sick animals are more vulnerable to mosquito bites, and increased virema increases the odds that a bite will infect the mosquito. In the (non-anthropod) host, death does not reduce transmission probabilities, as time to recovery and time to death are both 4-6 days.

Mosquitos hitchike on airplanes.

WNV- flavirivus

Bruce Aylward: How we'll stop polio for good

Bruce Aylward

A great man, with a great quest. We do have the little bastard on the run, and I agree, we MUST finish it off.

Polio took my father's brother at age 16.

Resistance pathways

We know virus develop resistance to drugs. The interesting cases are when resistance depends on combinations of mutations; mutational pathways.

The concept pathway implies an order. Is there one?
fitness landscapse or seascape?
survival of the fittest or the flattest?
colonizer/competitor dynamics?

What is a reference sequence? Does this define the virus???

Possible titles "Tracing evolutionary pathways through seascapes and bottlenecks"

hmmm-- ship in a bottle, early mariners, exploring, setting up trade outposts???

rates of HIV evolution

Prabhav suggested comparing rates of viral evolution within patients to those within a transmission cluster.

We could measure/compare rates of adoptation to treatment to rates of adoptation to a new host.

The confound is that we identify the transmission clusters via genetic distance. It would be easier if we had a known transmission chain.

Alternately, EuResist does have ~6000 cases with two samples taken under one treatment. We could compare rates here with rates after a treatment change.

NGS review/ Beerenwinkel

Ultra-deep sequencing for the analysis of viral populations
Beerenwinkel and Zagordi,
Curr Opin Virol 2011:1

Very general. Presents the process and challenges. Lists major software for haplotype identificaiton, but does not provide a comprehensive review of their capacities and differences.

filed under beerenwinkel_cov_2011.pdf

competition-colonization dynamics

Competition-colonization dynamics
An ecology approach to quasispecies dynamics and virulence evolution in RNA viruses
Samuel Ojosnegros, Niko Beerenwinkel, and Esteban Domingo

Not the first or best paper on the subject, just the one I read today. A single viral clone, raised in a pure cell culture, evolved into two differnt subpopulations. The phenotypes of the two clades clearly displayed either the competitor (less fit, less virulent, but interfered with replication of the other type) or the colonization (more fit, more virulent) strategy.

stored as ojosnegros2011.pdf

Joe DeRisi hunts for new virus in Africa

Joe DeRisi

Cooperates with bushmeat hunters in africa to get blood samples from them and their kill, to allow surveiliance for new disease