title: Differences in time of virus appearance in the blood and virus-specific immune responses in intravenous and intrarectal primary SIVmac251 infection of rhesus macaques; a pilot study.
abstract: BACKGROUND
  HIV-I can be transmitted by intravenous inoculation of contaminated blood or blood product or sexually through mucosal surfaces. Here we performed a pilot study in the SIVmac251 macaque model to address whether the route of viral entry influences the kinetics of the appearance and the size of virus-specific immune in different tissue compartments.
  
  
  METHODS
  For this purpose, of 2 genetically defined Mamu-A*01-positive macaques, 1 was exposed intravenously and the other intrarectally to the same SIVmac251 viral stock and virus-specific CD8+ T-cells were measured within the first 12 days of infection in the blood and at day 12 in several tissues following euthanasia.
  
  
  RESULTS
  Virus-specific CD8+ T-cell responses to Gag, Env, and particularly Tat appeared earlier in the blood of the animal exposed by the mucosal route than in the animal exposed intravenously. The magnitude of these virus-specific responses was consistently higher in the systemic tissues and GALT of the macaque exposed by the intravenous route, suggesting a higher viral burden in the tissues as reflected by the faster appearance of virus in plasma. Differences in the ability of the virus-specific CD8+ T-cells to respond in vitro to specific peptide stimulation were also observed and the greatest proliferative ability was found in the GALT of the animal infected by the intrarectal route.
  
  
  CONCLUSIONS
  These data may suggest that the natural mucosal barrier may delay viral spreading. The consequences of this observation, if confirmed in studies with a larger number of animals, may have implications in vaccine development.
authors.affiliation: Basic Research Laboratory, National Cancer Institute, 41/D804, Bethesda, Maryland, 20892, USA. veffa@helix.nih.gov
authors.forename: L
authors.initials: L
authors.lastname: Stevceva
authors.forename: E
authors.initials: E
authors.lastname: Tryniszewska
authors.forename: Z
authors.initials: Z
authors.lastname: Hel
authors.forename: J
authors.initials: J
authors.lastname: Nacsa
authors.forename: B
authors.initials: B
authors.lastname: Kelsall
authors.forename: R
authors.initials: R
authors.lastname: Washington Parks
authors.forename: G
authors.initials: G
authors.lastname: Franchini
mesh_terms: D000818:Animals; D018791:CD4 Lymphocyte Count; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000473:pathology; D002455:Cell Division; D004195:Disease Models, Animal; D008253:Macaca mulatta / Q000235:genetics; D010865:Pilot Projects; D016097:Simian Acquired Immunodeficiency Syndrome / Q000097:blood / Q000276:immunology / Q000821:virology*; D015302:Simian Immunodeficiency Virus / Q000502:physiology*