Evolutionary Medicine

Time trend and patterns of HIV-1 Virulence

On an evolutionary time scale, HIV is a recent pathogen in human populations, raising the possibility of further adaptation to its host, which may potentially affect also the virulence of the virus. We demonstrated that over a two-decade period clinical markers of virulence did not show a trend in the Swiss HIV Cohort Study (SHCS) but increased in the Italian MASTER cohort. We contributed to a meta-analysis that tested these trends robustly using results from several countries and found increasing virulence over three decades. We also observed that African descent was associated with slower CD4 cell count decline in treatment-naive patients of the SHCS.

An evolutionary paradigm for adaptive Immunity

In a comprehensive evolutionary Perspective, we proposed a functional classification for the adaptive systems of immunity across all life and argued that the origin of vertebrate adaptive immunity constituted a major transition in evolution. We also constructed a detailed evolutionary scenario for the transition.

Evolutionary Theory of Disease

We formulate hypotheses pertaining to the evolution of both infectious and non-communicable diseases. How did African monkey species evolve to tolerate SIV infection? Why do sexually transmitted infections often lead to infertility? Can members of our microbiome ‘mutiny’ against us when we are old or seriously ill? Is there an evolutionary logic behind the ability of some facultative pathogens in our microbiome to cause potentially fatal sepsis? Some complex traits of tumors seem to defy the traditional logic of ‘selfish’ evolution—how can we explain them?

Relevant publications

  • Müller, V.; Ledergerber, B.; Perrin, L.; Klimkait, T.; Furrer, H.; Telenti, A.; Bernasconi, E.; Vernazza, P.; Günthard, H.F.; Bonhoeffer, S.; et al. Stable Virulence Levels in the HIV Epidemic of Switzerland over Two Decades. AIDS 2006, 20, 889, doi:10.1097/01.aids.0000218553.51908.6b.
  • Müller, V.; Maggiolo, F.; Suter, F.; Ladisa, N.; Luca, A.D.; Antinori, A.; Sighinolfi, L.; Quiros-Roldan, E.; Carosi, G.; Torti, C. Increasing Clinical Virulence in Two Decades of the Italian HIV Epidemic. PLOS Pathogens 2009, 5, e1000454, doi:10.1371/journal.ppat.1000454.
  • Herbeck, J.T.; Müller, V.; Maust, B.S.; Ledergerber, B.; Torti, C.; Di Giambenedetto, S.; Gras, L.; Günthard, H.F.; Jacobson, L.P.; Mullins, J.I.; et al. Is the Virulence of HIV Changing? A Meta-Analysis of Trends in Prognostic Markers of HIV Disease Progression and Transmission. AIDS 2012, 26, 193, doi:10.1097/QAD.0b013e32834db418.
  • Müller, V.; von Wyl, V.; Yerly, S.; Böni, J.; Klimkait, T.; Bürgisser, P.; Ledergerber, B.; Günthard, H.F.; Bonhoeffer, S.; Study, the S.H.C. African Descent Is Associated with Slower CD4 Cell Count Decline in Treatment-Naive Patients of the Swiss HIV Cohort Study. AIDS 2009, 23, 1269, doi:10.1097/QAD.0b013e32832d4096.
  • Bertels, F.; Marzel, A.; Leventhal, G.; Mitov, V.; Fellay, J.; Günthard, H.F.; Böni, J.; Yerly, S.; Klimkait, T.; Aubert, V.; et al. Dissecting HIV Virulence: Heritability of Setpoint Viral Load, CD4+ T-Cell Decline, and Per-Parasite Pathogenicity. Molecular Biology and Evolution 2018, 35, 27–37, doi:10.1093/molbev/msx246.
  • Müller, V.; Boer, R.J.D. The Integration Hypothesis: An Evolutionary Pathway to Benign SIV Infection. PLOS Pathogens 2006, 2, e15, doi:10.1371/journal.ppat.0020015.
  • Apari, P.; Sousa, J.D. de; Müller, V. Why Sexually Transmitted Infections Tend to Cause Infertility: An Evolutionary Hypothesis. PLOS Pathogens 2014, 10, e1004111, doi:10.1371/journal.ppat.1004111.
  • Rózsa, L.; Apari, P.; Müller, V. The Microbiome Mutiny Hypothesis: Can Our Microbiome Turn against Us When We Are Old or Seriously Ill? Biol Direct 2015, 10, 3, doi:10.1186/s13062-014-0034-5.
  • Rózsa, L.; Apari, P.; Sulyok, M.; Tappe, D.; Bodó, I.; Hardi, R.; Müller, V. The Evolutionary Logic of Sepsis. Infection, Genetics and Evolution 2017, 55, 135–141, doi:10.1016/j.meegid.2017.09.006.
  • Müller, V.; De Boer, R.J.; Bonhoeffer, S.; Szathmáry, E. An Evolutionary Perspective on the Systems of Adaptive Immunity. Biological Reviews 2018, 93, 505–528, doi:10.1111/brv.12355.
  • Apari, P.; Müller, V. Paradoxes of Tumour Complexity: Somatic Selection, Vulnerability by Design, or Infectious Aetiology? Biological Reviews 2019, 94, 1075–1088, doi:10.1111/brv.12490.

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