Viruses : genetic elements encased in protein

1. Viruses: genetic elements encased in protein • Viruses cannot reproduce independently: they are missing several of the characteristics of living organisms (no cellular organization, no growth, no independent replication). • They do cause human diseases such as influenza, polio, smallpox, and AIDS. • They cause plant diseases: e.g., more than 900 viruses are known to infect crop plants. • They cause pet diseases such as rabies, Feline Leukemia (FeLV), Feline Immunodeficiency (FIV), Canine Distemper. • Genetic engineering: viruses can be used as a tool to move genes from one organism to another.

2. HPV, An Emerging Plant Virus • The high plains virus (HPV) was first found in 1993 infecting corn and winter wheat of the central and western USA. • By 1995, HPV was found to be widespread and cause severe symptoms or death of maize, wheat, barley, and several species of grasses. • HPV is one of a family of plant viruses that cause wheat spot mosaic, fig mosaic, thistle mosaic, rose rosette, and redbud yellow ringspot diseases • Aceria tosichella mite that transfers virus among plants. • Corn HPV resistance genes have already been mapped and may reduce mite feeding or the spread of the virus from the point of infection.

3. Seal Plague Virus • Seal Plague Virus (PDV) • Harbor seal, Phoca vitulina • 1988 Europe: population reduced to 4,000 animals by 1989. • 2002 Europe: death toll 22,000-30,000 animals out of a total harbor seal population of 88,000. Measles Porpoise morbillivirus Dolphin morbillivirus Canine distemper

4. Viruses Replicate in Two Ways • Lytic Cycle: invades a host cell, takes over the host’s DNA replication machinery, makes more viruses. Virions then lyse host cell to escape and infect other host cells. • Lysogenic Cycle: invades host cell, incorporates into host cell DNA, replicates with host cell DNA and is transmitted to descendant host cells like a host gene.

5. Types of Human Viral Diseases • “Hit and Run”: produce acute disease in the individual and a self-limiting epidemic in the human population, conferring immunity on infected surviving individuals. Examples: Influenza and smallpox. • “Recurrent Disease”: persists in latent form after initial infection and recurs during the life of the infected individual. Examples: Chicken pox (shingles later in life) and herpes. • “Endogenous Latency“: inserts into human germ cell lines and is transmitted from host parent to host offspring like genes for millions of generations. Examples: Human endogenous retroviruses (HERTs).

6. Endogenous Retroviruses • Endogenous retroviruses (ERVs) have invaded the germ-line cells of every species of vertebrate and are transmitted, like genes, as part of normal host reproduction. • 8% of the human genome consists of HERVs. • Host genomes are continually evolving new regulatory mechanisms to silence the mutagenic effects on host genes associated with the replication of HERVs. This results in a reciprocal selective pressure on the HERVs to evolve to escape the host controls. HERV genes are in here, ~ 8,000 base pairs 5’ LTR 3’ LTR Long Terminal Repeats (LTRs) are each ~1,000 base pairs

7. Evolution of LTRs of a Retrovirus Withina Single Species At the time of insertion into the host germ-line cells, the 5’ LTR and the 3’LTR are identical in gene sequence Host DNA 5’ LTR 3’ LTR Over time, Mutations Accumulate 5’ LTR ≠ 3’ LTR More time, Means More Mutations, which Means A Greater Difference Between 5’ and 3’ LTRs 5’ LTR ≠ ≠≠3’ LTR

8. Evolution of LTRs of an Endogenous Retrovirus BetweenTwo Species At the time of speciation from a common ancestor, the 5’ LTR’s are identical in gene sequence and so are the 3’LTRs Ancestor Species Daughter Species 1 Daughter Species 2 Mutations Mutations Mutations Mutations 5’ LTR of Species 1 ≠ ≠≠5’ LTR of Species 2 3’ LTR of Species1≠ ≠≠3’ LTR of Species 2

9. Phylogeny of Primate Endogenous Retroviruses Gorilla 5’ LTRs Human Chimpanzee Bonobo Present Gorilla Past Human 3’ LTRs Chimpanzee Bonobo

10. Human Immunodeficiency Virus (HIV), the cause of AIDS • HIVis a retrovirus (see Figure 26.5 in your text). • HIVis called a lenti virus, owing to the long time it takes to go from initial infection to disease. • It is transmitted from infected to uninfected persons by blood or semen. • There are two genetically different kinds of HIV circulating in the human population, HIV-1 and HIV-2 • Hypothesis: Humans acquired HIV by butchering and eating from other primates.

11. Testing the Hypothesis that Humans acquired HIV from other primates • Obtain SIV gene sequences from a variety of primate species. Simian Immunodeficiency Virus = SIV • Compare SIV gene sequences to HIV-1 and HIV-2 gene sequences. • The most similar DNA sequences share a more recent common ancestor. • The most recent common SIV ancestor is the source of HIV: HIV-1 Has a different origin than HIV-2.

12. Clade of Immunodeficiency Viruses using SIV genes African Green Monkey Sike’s Monkey Sooty Mangabey Mandrill HIV-2 HIV-1 Chimpanzee Support for the Hypothesis that Humans acquired HIV by butchering and eating from other primates.

13. Refinement of the Hypothesis of the Origin of HIV-1 • Which population of Chimpanzees did HIV-1 come from? • There are two chimpanzee subspecies in Africa: (1) Pan troglodytes troglodytes in central Africa; and, (2) P. t. schweinfurthii in eastern Africa. • SIVcpz-1 is genetically very divergent from SIVcpz-2, consistent with the sub-species designation and the geographic distance between the subspecies. Genetic and Bio-geographical Evidence for Sub-Specific origin of HIV-1 • All HIV-1 strains are closely related to SIVcpz-1. =Genetic Evidence. • The natural range of P. t. troglodytes coincides uniquely with areas where the Human population of Africa harbors HIV-1. = Geographic Evidence. Conclusion: These two patterns indicate that P. t. troglodytes is the primary zoonotic reservoir for HIV-1. • Additional genetic evidence (not shown) suggests that there have been at least three independent introductions of SIVcpz-1 into the human population!

14. Further testing of the Hypothesis • Genetic evidence supports the Hypothesis that HIVis a zoonotic infection, that is, our species has acquired HIV at least twice from another species. Once from the Chimpanzee and once from the Sooty Mangabey. • From the view-point of the virus, infecting our species is a host range expansion. • Additional Hypothesis: If Humans acquired HIV by eating ‘bush meat,’ then we should also carry other blood-borne viruses from these same primates.

15. Simian foamy viruses (SFVs) • Simian foamy viruses (SFVs) are ubiquitous, non-pathogenic, non-endogenous retroviruses that infect all primate species. • Vertically transmitted from mother to offspring, contagiously but not in the germline. • They have co-speciated with Old World Primates for over 30 million years: Every Old World Primate Has its OWN UNIQUE SFV.

16. Genetic Evidence of Mother-Offspring Contagious Transmission of SFV TREE or Clade from Primate Maternally Transmitted Mitochondrial DNA TREE or Clade from SFV Gene Sequence

17. No Human FV • All foamy virus infections identified in humans are of zoonotic origin and all have occurred in persons exposed to non-human primates, like zoo keepers. • Although humans share a common evolution with non-human primates and are susceptible to SFV infection, humans are notendemically infected with a species-specific FV like other primates. • Hypothesis: HFV became extinct in humans because of reduced transmissibility from mother to offspring. • Hypothesis: HFV exists endemically in some human populations but they have not yet been tested.