title: Serial human passage of simian immunodeficiency virus by unsterile injections and the emergence of epidemic human immunodeficiency virus in Africa.
abstract: There is compelling evidence that both human immunodeficiency virus (HIV) types emerged from two dissimilar simian immunodeficiency viruses (SIVs) in separate geographical regions of Africa. Each of the two HIVs has its own simian progenitor and specific genetic precursor, and all of the primates that carry these SIVs have been in close contact with humans for thousands of years without the emergence of epidemic HIV. To date no plausible mechanism has been identified to account for the sudden emergence in the mid-20th century of these epidemic HIVs. In this study we examine the conditions needed for SIV to complete the genetic transition from individual human SIV infections to epidemic HIV in humans. The genetic distance from SIV to HIV and the mutational activity needed to achieve this degree of adaptation to human hosts is placed within a mathematical model to estimate the probabilities of SIV completing this transition within a single SIV-infected human host. We found that the emergence of even one epidemic HIV strain, following a single human exposure to SIV, was very unlikely. And the probability of four or more such transitions (i.e. HIV-1 groups M, O and HIV-2 subtypes A and B) occurring in a brief period is vanishingly small. We conclude that SIV cannot become a zoonosis, but requires adaptive mutations to become HIV. Some modern event must have aided in the transition of SIV to HIV. Our research indicates that serial passage of partially adapted SIV between humans could produce the series of cumulative mutations sufficient for the emergence of epidemic HIV strains. We examined the rapid growth of unsterile injections in Africa beginning in the 1950s as a biologically plausible event capable of greatly increasing serial human passage of SIV and generating HIV by a series of multiple genetic transitions. We conclude that increased unsterile injecting in Africa during the period 1950-1970 provided the agent for SIV human infections to emerge as epidemic HIV in the modern era.
authors.affiliation: Aaron Diamond AIDS Research Center, The Rockefeller University, New York, NY 10016, USA. pmarx@adarc.org
authors.forename: P A
authors.initials: PA
authors.lastname: Marx
authors.forename: P G
authors.initials: PG
authors.lastname: Alcabes
authors.forename: E
authors.initials: E
authors.lastname: Drucker
mesh_terms: D000349:Africa / Q000453:epidemiology; D000818:Animals; D004196:Disease Outbreaks / Q000266:history*; D018562:Disease Transmission, Infectious / Q000266:history*; D015658:HIV Infections / Q000453:epidemiology / Q000266:history* / Q000635:transmission; D015497:HIV-1 / Q000235:genetics / Q000502:physiology*; D015498:HIV-2 / Q000235:genetics / Q000502:physiology; D049673:History, 20th Century; D006801:Humans; D007267:Injections / Q000266:history; D009154:Mutation; D010406:Penicillins / Q000008:administration & dosage; D010802:Phylogeny; D011336:Probability; D011634:Public Health; D016097:Simian Acquired Immunodeficiency Syndrome / Q000266:history / Q000635:transmission / Q000821:virology; D015302:Simian Immunodeficiency Virus / Q000235:genetics / Q000502:physiology*; D013242:Sterilization; D013594:Syringes
chemical_list: D010406:Penicillins