title: Phylogenetic analysis consistent with a clinical history of sexual transmission of HIV-1 from a single donor reveals transmission of highly distinct variants.
abstract: BACKGROUND
  To combat the pandemic of human immunodeficiency virus 1 (HIV-1), a successful vaccine will need to cope with the variability of transmissible viruses. Human hosts infected with HIV-1 potentially harbour many viral variants but very little is known about viruses that are likely to be transmitted, or even if there are viral characteristics that predict enhanced transmission in vivo. We show for the first time that genetic divergence consistent with a single transmission event in vivo can represent several years of pre-transmission evolution.
  
  
  RESULTS
  We describe a highly unusual case consistent with a single donor transmitting highly related but distinct HIV-1 variants to two individuals on the same evening. We confirm that the clustering of viral genetic sequences, present within each recipient, is consistent with the history of a single donor across the viral env, gag and pol genes by maximum likelihood and bayesian Markov Chain Monte Carlo based phylogenetic analyses. Based on an uncorrelated, lognormal relaxed clock of env gene evolution calibrated with other datasets, the time since the most recent common ancestor is estimated as 2.86 years prior to transmission (95% confidence interval 1.28 to 4.54 years).
  
  
  CONCLUSIONS
  Our results show that an effective design for a preventative vaccine will need to anticipate extensive HIV-1 diversity within an individual donor as well as diversity at the population level.
authors: Nuffield Department of Clinical Medicine, Peter Medawar Building for Pathogen Research, Oxford University, South Parks Road, Oxford, OX1 3SY, UK.
authors: Suzanne
authors: S
authors: English
authors: Aris
authors: A
authors: Katzourakis
authors: David
authors: D
authors: Bonsall
authors: Peter
authors: P
authors: Flanagan
authors: Anna
authors: A
authors: Duda
authors: Sarah
authors: S
authors: Fidler
authors: Jonathan
authors: J
authors: Weber
authors: Myra
authors: M
authors: McClure
authors: Rodney
authors: R
authors: Phillips
authors: John
authors: J
authors: Frater
mesh_terms: D015331:Cohort Studies; D005260:Female; D015658:HIV Infections / Q000635:transmission* / Q000821:virology*; D015497:HIV-1 / Q000145:classification* / Q000235:genetics / Q000302:isolation & purification; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D010802:Phylogeny; D014764:Viral Proteins / Q000235:genetics
chemical_list: D014764:Viral Proteins