title: Previously transmitted HIV-1 strains are preferentially selected during subsequent sexual transmissions.
abstract: BACKGROUND
  A genetic bottleneck is known to exist for human immunodeficiency virus (HIV) at the point of sexual transmission. However, the nature of this bottleneck and its effect on viral diversity over time is unclear.
  
  
  METHODS
  Interhost and intrahost HIV diversity was analyzed in a stable population in Rakai, Uganda, from 1994 to 2002. HIV-1 envelope sequences from both individuals in initially HIV-discordant relationships in which transmission occurred later were examined using Sanger sequencing of bulk polymerase chain reaction (PCR) products (for 22 couples), clonal analysis (for 3), and next-generation deep sequencing (for 9).
  
  
  RESULTS
  Intrahost viral diversity was significantly higher than changes in interhost diversity (P < .01). The majority of HIV-1-discordant couples examined via bulk PCR (16 of 22 couples), clonal analysis (3 of 3), and next-generation deep sequencing (6 of 9) demonstrated that the viral populations present in the newly infected recipient were more closely related to the donor partner's HIV-1 variants found earlier during infection as compared to those circulating near the estimated time of transmission (P = .03).
  
  
  CONCLUSIONS
  These findings suggest that sexual transmission constrains viral diversity at the population level, partially because of the preferential transmission of ancestral as opposed to contemporary strains circulating in the transmitting partner. Future successful vaccine strategies may need to target these transmitted ancestral strains.
authors.affiliation: Laboratory of Immunoregulation, Division of Intramural Research (DIR), National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, MD, USA.
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Redd
authors.forename: Aleisha N
authors.initials: AN
authors.lastname: Collinson-Streng
authors.forename: Nikolaos
authors.initials: N
authors.lastname: Chatziandreou
authors.forename: Caroline E
authors.initials: CE
authors.lastname: Mullis
authors.forename: Oliver
authors.initials: O
authors.lastname: Laeyendecker
authors.forename: Craig
authors.initials: C
authors.lastname: Martens
authors.forename: Stacy
authors.initials: S
authors.lastname: Ricklefs
authors.forename: Noah
authors.initials: N
authors.lastname: Kiwanuka
authors.forename: Phyu Hninn
authors.initials: PH
authors.lastname: Nyein
authors.forename: Tom
authors.initials: T
authors.lastname: Lutalo
authors.forename: Mary K
authors.initials: MK
authors.lastname: Grabowski
authors.forename: Xiangrong
authors.initials: X
authors.lastname: Kong
authors.forename: Jordyn
authors.initials: J
authors.lastname: Manucci
authors.forename: Nelson
authors.initials: N
authors.lastname: Sewankambo
authors.forename: Maria J
authors.initials: MJ
authors.lastname: Wawer
authors.forename: Ronald H
authors.initials: RH
authors.lastname: Gray
authors.forename: Stephen F
authors.initials: SF
authors.lastname: Porcella
authors.forename: Anthony S
authors.initials: AS
authors.lastname: Fauci
authors.forename: Manish
authors.initials: M
authors.lastname: Sagar
authors.forename: David
authors.initials: D
authors.lastname: Serwadda
authors.forename: Thomas C
authors.initials: TC
authors.lastname: Quinn
mesh_terms: D000293:Adolescent; D000328:Adult; D016000:Cluster Analysis; D005260:Female; D014644:Genetic Variation; D015658:HIV Infections / Q000635:transmission* / Q000821:virology*; D015497:HIV-1 / Q000145:classification* / Q000235:genetics / Q000302:isolation & purification / Q000472:pathogenicity*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010802:Phylogeny; D016133:Polymerase Chain Reaction; D012367:RNA, Viral / Q000235:genetics; D012641:Selection, Genetic; D017422:Sequence Analysis, DNA; D014454:Uganda; D055815:Young Adult
chemical_list: D012367:RNA, Viral