title: Human immunodeficiency viruses appear compartmentalized to the female genital tract in cross-sectional analyses but genital lineages do not persist over time.
abstract: BACKGROUND
  Whether unique human immunodeficiency type 1 (HIV) genotypes occur in the genital tract is important for vaccine development and management of drug resistant viruses. Multiple cross-sectional studies suggest HIV is compartmentalized within the female genital tract. We hypothesize that bursts of HIV replication and/or proliferation of infected cells captured in cross-sectional analyses drive compartmentalization but over time genital-specific viral lineages do not form; rather viruses mix between genital tract and blood.
  
  
  METHODS
  Eight women with ongoing HIV replication were studied during a period of 1.5 to 4.5 years. Multiple viral sequences were derived by single-genome amplification of the HIV C2-V5 region of env from genital secretions and blood plasma. Maximum likelihood phylogenies were evaluated for compartmentalization using 4 statistical tests.
  
  
  RESULTS
  In cross-sectional analyses compartmentalization of genital from blood viruses was detected in three of eight women by all tests; this was associated with tissue specific clades containing multiple monotypic sequences. In longitudinal analysis, the tissues-specific clades did not persist to form viral lineages. Rather, across women, HIV lineages were comprised of both genital tract and blood sequences.
  
  
  CONCLUSIONS
  The observation of genital-specific HIV clades only in cross-sectional analysis and an absence of genital-specific lineages in longitudinal analyses suggest a dynamic interchange of HIV variants between the female genital tract and blood.
authors: Department of Pediatrics. University of Washington, Seattle, WA 98101, USA.
authors: Marta E
authors: ME
authors: Bull
authors: Laura M
authors: LM
authors: Heath
authors: Jennifer L
authors: JL
authors: McKernan-Mullin
authors: Kelli M
authors: KM
authors: Kraft
authors: Luis
authors: L
authors: Acevedo
authors: Jane E
authors: JE
authors: Hitti
authors: Susan E
authors: SE
authors: Cohn
authors: Kenneth A
authors: KA
authors: Tapia
authors: Sarah E
authors: SE
authors: Holte
authors: Joan A
authors: JA
authors: Dragavon
authors: Robert W
authors: RW
authors: Coombs
authors: James I
authors: JI
authors: Mullins
authors: Lisa M
authors: LM
authors: Frenkel
mesh_terms: D003430:Cross-Sectional Studies; D005260:Female; D005814:Genes, Viral; D005836:Genitalia, Female / Q000821:virology*; D005838:Genotype; D006031:Glycosylation; D015658:HIV Infections / Q000097:blood* / Q000473:pathology / Q000821:virology; D015497:HIV-1 / Q000235:genetics / Q000472:pathogenicity* / Q000502:physiology; D006801:Humans; D016013:Likelihood Functions; D008137:Longitudinal Studies; D010802:Phylogeny; D012367:RNA, Viral / Q000032:analysis / Q000235:genetics; D060737:Reproductive Tract Infections / Q000097:blood / Q000473:pathology / Q000821:virology; D017423:Sequence Analysis, RNA; D013045:Species Specificity; D013997:Time Factors; D014779:Virus Replication; D054299:env Gene Products, Human Immunodeficiency Virus / Q000097:blood / Q000235:genetics* / Q000378:metabolism
chemical_list: D012367:RNA, Viral; D054299:env Gene Products, Human Immunodeficiency Virus