title: Relative transmissibility of an R5 clade C simian-human immunodeficiency virus across different mucosae in macaques parallels the relative risks of sexual HIV-1 transmission in humans via different routes.
abstract: BACKGROUND
  Worldwide, approximately 90% of all human immunodeficiency virus (HIV) transmissions occur mucosally; almost all involve R5 strains. Risks of sexual HIV acquisition are highest for rectal, then vaginal, and finally oral exposures.
  
  
  METHODS
  Mucosal lacerations may affect the rank order of susceptibility to HIV but cannot be assessed in humans. We measured relative virus transmissibility across intact mucosae in macaques using a single stock of SHIV-1157ipd3N4, a simian-human immunodeficiency virus encoding a primary R5 HIV clade C env (SHIV-C).
  
  
  RESULTS
  The penetrability of rhesus macaque mucosae differed significantly, with rectal challenge requiring the least virus, followed by vaginal and then oral routes (P = .031, oral vs vaginal; P < .001 rectal vs vaginal). These findings imply that intrinsic mucosal properties are responsible for the differential mucosal permeability. The latter paralleled the rank order reported for humans, with relative risk estimates within the range of epidemiological human studies. To test whether inflammation facilitates virus transmission--as predicted from human studies--we established a macaque model of localized buccal inflammation. Systemic infection occurred across inflamed but not normal buccal mucosa.
  
  
  CONCLUSIONS
  Our primate data recapitulate virus transmission risks observed in humans, thus establishing R5 SHIV-1157ipd3N4 in macaques as a robust model system to study cofactors involved in human mucosal HIV transmission and its prevention.
authors.affiliation: Dana-Farber Cancer Institute, Massachusetts General Hospital, Boston, Massachusetts 02115-6084, USA.
authors.forename: Agnès L
authors.initials: AL
authors.lastname: Chenine
authors.forename: Nagadenahalli B
authors.initials: NB
authors.lastname: Siddappa
authors.forename: Victor G
authors.initials: VG
authors.lastname: Kramer
authors.forename: Gaia
authors.initials: G
authors.lastname: Sciaranghella
authors.forename: Robert A
authors.initials: RA
authors.lastname: Rasmussen
authors.forename: Sandra J
authors.initials: SJ
authors.lastname: Lee
authors.forename: Michael
authors.initials: M
authors.lastname: Santosuosso
authors.forename: Mark C
authors.initials: MC
authors.lastname: Poznansky
authors.forename: Vijayakumar
authors.initials: V
authors.lastname: Velu
authors.forename: Rama R
authors.initials: RR
authors.lastname: Amara
authors.forename: Chris
authors.initials: C
authors.lastname: Souder
authors.forename: Daniel C
authors.initials: DC
authors.lastname: Anderson
authors.forename: François
authors.initials: F
authors.lastname: Villinger
authors.forename: James G
authors.initials: JG
authors.lastname: Else
authors.forename: Francis J
authors.initials: FJ
authors.lastname: Novembre
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Strobert
authors.forename: Shawn P
authors.initials: SP
authors.lastname: O'Neil
authors.forename: W Evan
authors.initials: WE
authors.lastname: Secor
authors.forename: Ruth M
authors.initials: RM
authors.lastname: Ruprecht
mesh_terms: D000818:Animals; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes; D018450:Disease Progression; D004198:Disease Susceptibility / Q000821:virology; D005260:Female; D015658:HIV Infections / Q000635:transmission; D015497:HIV-1 / Q000472:pathogenicity*; D006801:Humans; D007249:Inflammation / Q000821:virology; D007413:Intestinal Mucosa / Q000821:virology; D008253:Macaca mulatta / Q000821:virology; D009061:Mouth Mucosa / Q000821:virology; D009092:Mucous Membrane / Q000821:virology*; D012007:Rectum / Q000821:virology; D016097:Simian Acquired Immunodeficiency Syndrome / Q000635:transmission*; D015302:Simian Immunodeficiency Virus / Q000472:pathogenicity*; D014621:Vagina / Q000821:virology; D019562:Viral Load