title: Evaluation of cervical mucosa in transmission bottleneck during acute HIV-1 infection using a cervical tissue-based organ culture.
abstract: BACKGROUND
  Although there are different strains of HIV-1 in a chronically infected individual, only one or limited virus strains are successfully transmitted to a new individual. The reason for this "transmission bottleneck" is as yet unknown.
  
  
  RESULTS
  A human cervical explant model was used to measure HIV-1 transmission efficiency of viral strains from chronic infections, and transmitter/founder variants. We also evaluated the genetic characteristics of HIV-1 variants in the inoculums compared to those transmitted across the cervical mucosa. Eight different HIV-1 isolates were used in this study, six chronic isolates and two transmitter/founder viruses. The transmission efficiency of the chronic and transmitter/founder virus isolates and the viral diversity of chronic isolates before and after viral transmission were assessed. The results indicate that transmitter/founder viruses did not display higher transmission efficiency than chronic HIV-1 isolates. Furthermore, no evidence for a difference in diversity was found between the inoculums and transmitted virus strains. Phylogenetic analysis indicated that the sequences of variants in the inoculums and those present in transmitted virus intermingled irrespective of co-receptor usage. In addition, the inoculum and transmitted variants had a similar pairwise distance distribution.
  
  
  CONCLUSIONS
  There was no selection of a single or limited number of viral variants during HIV-1 transmission across the cervical mucosa in the organ culture model, indicating that the cervical mucosa alone may not produce the transmission bottleneck of HIV-1 infection observed in vivo.
authors.affiliation: Department of Infectious Diseases and Microbiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America.
authors.forename: Chengli
authors.initials: C
authors.lastname: Shen
authors.forename: Ming
authors.initials: M
authors.lastname: Ding
authors.forename: Deena
authors.initials: D
authors.lastname: Ratner
authors.forename: Ronald C
authors.initials: RC
authors.lastname: Montelaro
authors.forename: Yue
authors.initials: Y
authors.lastname: Chen
authors.forename: Phalguni
authors.initials: P
authors.lastname: Gupta
mesh_terms: D001483:Base Sequence; D002584:Cervix Uteri / Q000276:immunology / Q000821:virology*; D005260:Female; D015658:HIV Infections / Q000276:immunology / Q000635:transmission*; D015497:HIV-1 / Q000145:classification / Q000235:genetics / Q000276:immunology; D006801:Humans; D008969:Molecular Sequence Data; D009092:Mucous Membrane / Q000276:immunology / Q000821:virology; D009924:Organ Culture Techniques; D010802:Phylogeny; D054299:env Gene Products, Human Immunodeficiency Virus / Q000235:genetics
chemical_list: D054299:env Gene Products, Human Immunodeficiency Virus