title: Time-measured phylogenies of gag, pol and env sequence data reveal the direction and time interval of HIV-1 transmission.
abstract: OBJECTIVE
  To investigate whether time-measured phylogenetic analysis of longitudinal viral sequences can establish the direction and timing of HIV-1 transmission in an epidemiologically linked transmission cluster of three homosexual men.
  
  
  METHODS
  An HIV-1-infected homosexual man (patient 1) and his long-term HIV-negative partner (patient 2) engaged in a triangular relationship with an additional partner (patient 3). On the basis of phylogenetic analysis of gag sequences, patient 3 was previously identified as the source for superinfection of patient 1 but the source of HIV-1 infection of patient 2, who seroconverted during the triangular relationship, remained unclear. Here, we set out to analyze newly obtained gag, pol and env sequences from all three patients to fully elucidate the transmission history in this epidemiologically linked cluster.
  
  
  METHODS
  Bayesian Markov Chain Monte Carlo (MCMC) phylogenetic analyses incorporating a relaxed clock model and a flexible Bayesian skyride tree prior were applied to the longitudinally obtained gag, pol and env sequences from all three patients.
  
  
  RESULTS
  Our time-measured evolutionary reconstructions convincingly supported transmission of HIV-1 from the new partner patient 3 to both patients 1 and 2. In addition, estimates of viral divergence times assisted in narrowing down the transmission intervals delineated by seroconversion estimates.
  
  
  CONCLUSIONS
  Our analysis implies that Bayesian MCMC phylogenetic reconstruction incorporating temporal information can indeed reveal the direction of multiple HIV-1 transmission events in an epidemiologically linked cluster and provide more detail on the timing of transmission.
authors.affiliation: Department of Experimental Immunology, Sanquin Research, Landsteiner Laboratory, and Center for Infection and Immunity Amsterdam (CINIMA) at the Academic Medical Center of the University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Andrea
authors.initials: A
authors.lastname: Rachinger
authors.forename: Paul H P
authors.initials: PH
authors.lastname: Groeneveld
authors.forename: Sander
authors.initials: S
authors.lastname: van Assen
authors.forename: Philippe
authors.initials: P
authors.lastname: Lemey
authors.forename: Hanneke
authors.initials: H
authors.lastname: Schuitemaker
mesh_terms: D001499:Bayes Theorem; D015752:Genes, env / Q000235:genetics*; D015750:Genes, gag / Q000235:genetics*; D015751:Genes, pol / Q000235:genetics*; D015658:HIV Infections / Q000235:genetics* / Q000635:transmission; D015497:HIV-1 / Q000235:genetics*; D006716:Homosexuality; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D010802:Phylogeny; D012367:RNA, Viral / Q000235:genetics*; D012725:Sexual Behavior; D012747:Sexual Partners / Q000145:classification
chemical_list: D012367:RNA, Viral