Ex vivo modeling of oral HIV transmission in human palatine tonsil.
The majority of newly acquired HIV infections are believed to occur following transmission of virus infectivity across mucosal surfaces, although many mechanistic details still remain unresolved. We have used human ex vivo organ cultures and primary cell populations to analyze the cellular and molecular basis for mucosal HIV transmission. By using human palatine tonsil from routine tonsillectomies and semen from HIV-positive donors, we have created an experimental equivalent to oral HIV transmission. HIV infection was readily transferred into tonsillar lymphocytes, but this transmission into lymphocytes was dramatically reduced when the exposed lymphocyte populations were protected by intact mucosal surfaces. In this study, we consider the impact that leukocyte activation and morphological aberrations in surface structure may have on susceptibility to primary HIV infection and introduce novel time-lapse confocal microscopy procedures that begin to reveal the dynamic complexity associated with cell-mediated HIV transmission.
Maher
Diane M
DM
Department of Microbiology, MMC 196, University of Minnesota, 420 Delaware Street SE, Minneapolis, MN 55455, USA.
Zhang
Zhi-Qiang
ZQ
Schacker
Timothy W
TW
Southern
Peter J
PJ
D006678:HIV / Q000235:genetics / Q000502:physiology; D015658:HIV Infections / Q000635:transmission*; D006679:HIV Seropositivity / Q000635:transmission; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008214:Lymphocytes / Q000821:virology; D008855:Microscopy, Electron, Scanning; D009055:Mouth / Q000821:virology; D009924:Organ Culture Techniques; D014066:Palatine Tonsil / Q000648:ultrastructure / Q000821:virology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012661:Semen / Q000821:virology; D014779:Virus Replication