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Co-evolution

Co-evolution. 1995. Host-pathogen (co-)evolution. Host-pathogen co-evolution. Virus A. Primate A. Primate B. Virus B. Primate C. Virus C. Host-pathogen co-evolution in other SIV. Divergent lineages of SIV have also been found in African green monkeys. African green monkeys.

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Co-evolution

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  1. Co-evolution

  2. 1995 Host-pathogen (co-)evolution

  3. Host-pathogen co-evolution Virus A Primate A Primate B Virus B Primate C Virus C

  4. Host-pathogen co-evolution in other SIV Divergent lineages of SIV have also been found in African green monkeys

  5. African green monkeys These primates have a broad distribution throughout sub-Saharan Africa and have been classified based on phenotypic differences into four major species:

  6. 1. vervet (Chlorocebus pygerythrus). ETYMOLOGY:French: vert = green 2. grivet (C. aethiops) 3. sabaeus (C. sabaeus) 4. tantalus (C. tantalus).

  7. Virus A Primate A Primate B Virus B Primate C Virus C Host-pathogen co-evolution in other SIV The many SIVagm strains infecting these animals cluster into four distinct phylogenetic lineages according to their species origin, indicating ancient infection followed by co-evolution of virus and host.

  8. Co-evolution between HIV-1 and SIVcpz? One possibility is that the ancestor of human and chimp had a virus, and that the virus split with the human-chimp split… (1990)

  9. 1999-Marilyn

  10. 1999

  11. 1999. Nature

  12. The natural host of HIV-1 • There are several doubts casting the theory that chimpanzees are the natural host and reservoir for HIV-1 • There is a wide spectrum of diversity between HIV-1 and SIVcpz. • An apparent low prevalence of SIVcpz infection in wild-living animals. • The presence of chimpanzees in geographic regions of Africa where AIDS was not initially recognized.

  13. Unidentified virus as the origin? Rather, it has been suggested that another, yet unidentified, primate species could be the natural host for SIVcpz and HIV-1.

  14. Marilyn “We recently identified a fourth chimpanzee with natural SIVcpz infection. This animal (Marilyn) was wild-caught in Africa (county of origin unknown), exported to the United States as an infant, and used as a breeding female in a primate facility until her death at age 26.”

  15. How this SIV was found? During a serosurvey in 1985, Marilyn was the only chimpanzee of 98 tested who had antibodies strongly reactive with HIV-1 by enzyme-linked immunosorbent assay (ELISA) and western immunoblot.

  16. An alternative explanation Maybe she was infected with HIV during her stay in the STATES? “She has never been used in AIDS research and had not received human blood products after 1969. She died in 1985 after giving birth to still-born twins.”

  17. Chimps do not develop AIDS To convince that she did not have AIDS… “An autopsy revealed endometritis, retained placental elements and sepsis as the final cause of death. Depletion of lymhoid tissues was not noted.” Endometritis: דלקת רירית הרחם Sepsis:אלח דם

  18. No virus could be isolated An ultimate proof that the virus is SIV could be the isolation of the virus and infecting chimpanzee cells in the lab. However, virus isolation from the autopsy tissues was unsuccessful… Failed…

  19. But sequencing worked! PCR was used to amplify a complete proviral genome. The genome was termed SIVcpzUS. Provirus The "provirus" is the form of the virus which is capable of being integrated into the host genome. In the case of HIV it means the DNA "copy" of the HIV genome (HIV normally carries its genes around in RNA form).

  20. HIV-1 and SIVcpz have similar genomes • Analysis of potential coding regions revealed the presence of a vpu gene. Vpu is only found in HIV-1 and SIVcpz viruses • Promoter and enhancer elements of the SIVcpzUS long terminal repeat (LTR) were indistinguishable from those of other members of the HIV-1/SIVcpz group.

  21. Only three other SIVcpz strains have been reported: Two from animals wild-caught in Gabon (SIVcpzGAB1 and SIVcpzGAB2) One from a chimpanzee exported to Belgium from Zaire (SIVcpzANT). (1990 paper) (SIVcpzGAB1 and SIVcpzANT have been sequenced completely, but only 280bp of the pol sequence are available for SIVcpzGAB2)

  22. Phylogenetic tree NJ tree HIV-1 + SIVcpz are monophyletic  Only bootstrap values >80% are shown  0.1 amino-acid replacements per site 

  23. Phylogenetic tree NJ tree There are at least two different HIV-1 clades, and two different SIVcpz clades

  24. Zooming in – chimpanzee subspecies From which chimpanzee subspecies the virus came from? [chimp = Pan troglodytes]. Four chimpanzee subspecies with non-overlapping geographic ranges are known: 1. The western P. t. verus. 2. Nigerian P. t. vellerosus. 3. Central P. t. troglodytes. 4. Eastern P. t. schweinfurthii.

  25. Geographic distribution of chimpanzee subspecies

  26. Zooming in – chimpanzee subspecies Question: how to find the chimpanzee subspecies from which HIV-1 was transferred to human? This is important, as it can tell us where the epedimic started…

  27. Marilyn again! The idea: Sequence Marilyn (the HOST) and test to which subspecies she belongs. This can be done by comparing the DNA of the infected chimps to the DNA of characterized chimp subspecies…

  28. Marilyn again! 1. A fragment of the mitochondrial control region (D-loop) was sequenced. 2. It was sequenced from all four infected chimps. 3. Sequences were compared to sequences from the 4 chimp subspecies.

  29. The three chimpanzees infected with the more closely related SIVcpzGAB1 (GAB1), SIVcpzGAB2 (GAB2), and SIVcpzUS (Marilyn) strains all belonged to the P. t. troglodytes subspecies. SIVcpzANT strain (Noah) was identified as a member of the P. t. schweinfurthii subspecies

  30. Conclusions Marilyn (SIVcpzUS) and GAB1 are close to HIV-1 and belong to P.t.t -> probably HIV-1 originated from P.t.t

  31. Origin - geography GAB1 GAB2 Marilyn NOA

  32. HIV-1 subtypes Globally circulating strains of HIV-1 have been classified into three major phylogenetic groups, termed M, N and O. All of which cause AIDS. The 'main' group M is responsible for the global AIDS epidemic and comprises by far the majority of HIV-1 isolates. These viruses have been further subdivided based on phylogenetic relatedness into ten distinct subtypes or clades, termed A–J.

  33. HIV-1 subtypes O and N Group O (for 'outlier') is represented by many fewer isolates that originate mainly from Cameroon, Gabon and Equatorial Guinea. Group N (for 'non-M/non-O') was discovered only very recently and is the least widespread of all HIV-1 lineages; so far, it has been documented in only two individuals from Cameroon.

  34. Marylin and friends may explain subtypes M and N. Origin of O – unclear.

  35. Intermediate summary 1999: HIV-1 infection of humans occurred as a result of cross-species transmission of SIVcpz from P. t. troglodytes. Probably explaining the origin of subtypes M and N.

  36. Origin of SIVcpz

  37. 2003 SIVcpz

  38. 2003. Science

  39. SIVcpz origin A part of SIVcpz (the pol gene) is closer to SIVrcm, and another part (env) is closer to SIVgsn

  40. A part of SIVcpz (the pol gene) is closer to SIVrcm, and another part (env) is closer to SIVgsn rcm = red-capped mangabeys (Cercocebus torquatus) Gsn=greater spot-nosed monkeys (Cercopithecus nictitans)

  41. SIVcpz origin Differences from the SIVcpz gene. and in others, the red is closest (SIVgsn). The red = SIVgsn is closest to SIVcpz The blue = SIVrcm is closest to SIVcpz

  42. SIVcpz origin – from recombination A recombination event at the Pol-Env junction led to the creation of SIVcpz…

  43. The river

  44. HIV

  45. Hooper, a well known scientist claimed that the AIDS virus (type 1) has crossed into humans as a result of contamination of the oral polio vaccine (OPV). The OPV/AIDS theory claims that chimpanzees from the vicinity of Kisangani in Congo were the source of SIVcpz that was transmitted to humans when chimpanzee tissues were used in the preparation of OPV. 1999

  46. Nature 2004

  47. Nature 2004

  48. Nature 2004 Nature 2004 They isolated SIV from urine samples of chimpanzees in the vicinity of Kisangani, where the polio vaccines were given. They found that the SIV in this region is of a chimpanzee subtype called Pan troglodytes schweinfurthii (pts) and not Pan troglodytes troglodytes (ptt).

  49. HIV-1 subtypes M, N, and O all cluster within SIVcpzPtt (green) while SIV from chimps within the red area (of Polio vaccine) clusters within SIVcpzPts (red). Conclusion: “The molecular epidemiological data presented here… should finally lay the OPV/AIDS theory to rest”.

  50. Subtype O origin

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