Phylogenies and Emerging Viruses

Biodiversity part 1: Germs: Viruses Distinguish between biodiversity and its role in disease epidemics/pandemics Influential in shaping human populations Case study: HIV Phylogenies and Emerging Viruses Virus evolutionary history - to determine if an emerging virus has jumped to a new host Phylogeny for HIV: 3 findings 1. Immunodeficiency viruses 2. 2 distinct types of human HIV HIV-1 and HIV-2 3. Multiple jumps have occurred Several strains of HIV-1, suggesting that it has jumped between species several times The multiple jumps of HIV-zoogenesis

Best treatments to HIV Better understanding of evolution, and ecology of the disease 3 directions/questions Evolutionary history of HIV? 2. Why are some people resistant to HIV and their respective strains? 3. How can we limit and control HIVs resistance based upon its evolution? 1. Evolutionary history of HIV VIRUS?

Closely related to other viruses SIV (simian immunodeficiency virus) Affects primates Distantly relatedFIV (felinescats) Distinctive patterns Populations of primates with SIV (and felines with FIV) are not regularly harmed by the virus.

Why are some individuals (and populations) resistant to HIV? CCR5 gene Chromosome 3 Mutation in CCR5 allele began in N. Europe (7000 y) Occurred after a plague (from other pathogen) Survivorsresistant to disease How can we limit and control HIVs resistance based upon its evolution? Rapid evolution Many drugs for HIV inhibits replicative growth Virion survivors become resistant to initial drug trial

Drug cocktails prescription Ex. A single drug might promote a couple of surviving virions Ex. Several drugs delay the evolution of the virus Example of drug cocktail Combination Brand name Food Date of FDA restrictions and approval notes EFV + TDF +

FTC Atripla Take on an empty stomach 12-Jul-06 d4T + 3TC + NVP - Take with or without food Tentative only*

AZT + 3TC+ NVP - Take with or without food Tentative only* TITLE TEMP TEMP TEMP

avert.org HIV origins and SIV research http://www.youtube.com/v/anxyLsA2T58 Keele et al. (2006) Populations of chimpanzees (note Sanaga River ) SIV populations gave rise to HIV strain M SIV populations gave rise to HIV strain N

SIV populations on this side of river-- no evolution to HIV strain O Sanaga River barrier Keele et al. (2006) The recent history of HIV High mutation rate Kinshasa (DRC) HIV sequence subtype

SIV populations gave rise to HIV strain M SIV populations gave rise to HIV strain N M (1960) 95% of infections worldwide 1959 sequence difference ~12% Late 1880s/early

1900s HIV group M took form HIV-2 (note, no apes) Tissue sample (lymph node) from 1960 Kinshasa woman Livingstone falls, lower Congo River basin https://www.youtube.com/watch?v=phTwbQPrt7c Congo River

Ancient river, ancient species Matadi-Kinshasa portage railway: creation of a new state Kinshasa (formerly Leopoldville) replaced Boma as capital during the phase of the Congo Free State (19081926) Alternative route to Livingstone Falls New capital because bustling center of trade/commerce

The spread Bushmeat trade Chimpanzee populations in West-Central Africa hunted for food Some chimps had SIV (strains) Butchering allowed hunters to be exposed to SIV Cameroonhuman individual carried the virus to the capital of the present-day DRC Bushmeat trade

Bushmeat market Sex trade Central Africa since the 1900s Rwandan genocide, 1994 HIV to the U.S. Reported case1981 In N. America, subtype B most common. Most likely introduced in the 1960s/1970s from Hispaola World map and HIV-1 strains

Recent news Protective alleles for HIV susceptibility in Biaka pygmies in Central Africa Carry genotypes protective against some genes like CCR5 Lived for a long time sympatrically with P. troglodytes populations with SIV that are most similar/analogous with HIV-1 m sequences HIV and children, orphans

Africa has more than 10 million children who lost their parents due to AIDS Education South Africa, Sesame Street introduced Kami character as an AIDS orphan HIV, population genetics In the mid-1990's, researchers discovered that despite repeated exposure to HIV-1, a strain of the Human immunodeficiency virus (HIV), some individuals remained

uninfected (Samson et al., 1996). More investigation revealed the existence of an allele that gives immunity to HIV-1 infection in homozygotes. This allele, known as ccr-5, is a mutant version of the cell-surface protein CCR-5. It inhibits HIV infection because it codes for a form of the CCR-5 protein to which HIV-1 viruses are unable to bind and, thus, to enter white blood cells and establish an infection (Samson et al., 1996). This allele is found most commonly in Caucasian Europeans and is absent or virtually absent from African, Asian, Middle Eastern, and American Indian populations (Galvani and Slatkin, 2003). Table 1 contains original data from Samson et al. (1996) documenting the genotypes of 704 Caucasian Europeans. Use these data to answer the questions that follow. CCR5 Map CCR5 (chromosome 3)

Genotype Number of Individuals CCR-5/CCR-5 (p2) 582 CCR-5/ccr-5 (2pq) 114 ccr-5/ccr-5 (q2) 8 Total

704 Table 1: Table 1: The number of individuals homozygous for either the CCR-5 (normal) or ccr-5 (mutant) allele or heterozygous for these two alleles in a sample of 704 Caucasian Europeans. Smallpox Example: smallpox Smallpox has been eradicated by vaccination programs and is currently extinct in the wild 9 of 10 deaths in the New World during the 16th century Parasitize a wide variety of hosts (exception: land plants)

-ssRNA Viruse Family a wide variety of hosts: flu, measles, rabies, and Ebola in humans Influenza Nipah (Henipavirus) Case fatality rate: 50% Disease linked to pigs and bats Symptoms: 3-14 days fever/headache Inflammation of brain, hallucinations Progresses to coma in 24-

48 hrs Food tainted via bat feces Outbreaks in India, SE Asia No treatments, vaccines H1N1 Flu (influenza) Virus Cast fatality rate: dependent on strains Bird flu-H5N1 54% case fatality rate Symptoms: fever-like Pneumonia/respiratory failure Strain in 1918-Spanish

flu killed millions Zebov (Zaire population Ebola) Case fatality rate: 83% Origin: West and Central Africa Transmission: fruit bats (most likely) Symptoms: fever higher than 101F Heavy bleeding of mucous membranes occurs later (eyes, intestines) 2014 outbreak: largest

known 2014 Outbreak (U.S. and Spain) Screening Travel Virus (incubation21 days) Flu like symptoms can be masked via Tynelol Genetic test Ebola virions $$$ Nina Pham Nurse contracted virus Recovered due to convalescent serum

Blood plasma via Dr. Kent Bradley, survived virus Treated young child from Liberia Blood rich in antibodies Rabies (Lyssavirus) Case fatality rate: > 90% Today 100% preventable Vaccine Long incubation rate (2-3 months) Education Symptoms: flu-like, targets CNS, fear of water

(hydrophobia) because of the difficulty in swallowing, severe pain (abdominal), brain swelling Bats (carrier) Measles (Morbilivirus) Virtually eliminated in N. America in early 2000s Recently (2014) bounced back Prevention requires > 90% of population vaccinated California (cases) leads

nation Miscommunication with medical/science personnel Few vaccinations Falsely linked autism Fear/hysteria Communities of >$80,000 average income Measles outbreak Retroviruses: Lentiviruses retroviruses infect only vertebratesbirds, fish, and mammals The most familiar and deadliest retrovirus is

HIV Chromosome 1 2 3 4 5 6 7 8 9 10 11 12 13 14

15 16 17 18 19 20 21 22 X Y mtDNA TOTAL Known genes: Pseudogenes: Length (mm) 85

Confirmed Putative Centromere Pseudogenes proteins proteins position (Mbp) 249,250,621 2,012 31 1,130 125 Base pairs 83 243,199,373

1,203 50 948 93.3 67 198,022,430 1,040 25 719

91 65 191,154,276 718 39 698 50.4 62 180,915,260

849 24 676 48.4 58 171,115,067 1,002 39 731

61 54 159,138,663 866 34 803 59.9 50 146,364,022

659 39 568 45.6 48 141,213,431 785 15 714

49 46 135,534,747 745 18 500 40.2 46 135,006,516

1,258 48 775 53.7 45 133,851,895 1,003 47 582

35.8 39 115,169,878 318 8 323 17.9 36 107,349,540

601 50 472 17.6 35 102,531,392 562 43 473