title: Early SIV Dissemination After Intrarectal SIVmac251 Challenge Was Associated With Proliferating Virus-Susceptible Cells in the Colorectum.
abstract: OBJECTIVE
  Few studies have examined the eclipse time of simian immunodeficiency virus/HIV infection through the anal route. We aimed to measure the eclipse time after SIVmac251 intrarectal inoculation, and to investigate the factor(s) associated with early dissemination.
  
  
  METHODS
  Forty macaques were intrarectally challenged with SIVmac251 3 times at 2-week intervals.
  
  
  METHODS
  Plasma viral RNA was monitored at 4, 7, 11, 14, 21, and 28 days after infection. Rectal/vaginal tissues were obtained and tissue viral loads (VLs) were measured at day 14 postinfection.
  
  
  RESULTS
  Of 40 macaques 26 (65%) had first detectable viral RNAs in the plasma at day 7 after the challenge that led to productive infection. Strikingly, 6 animals (15%) had detectable viral RNA in the plasma as early as at day 4. The Ki67 viral target CD4 T cells in the colorectal tissues were significantly higher in the early or middle-transmitter groups than those in the late-transmitter group. The rectal VL did not correlate with plasma VL at 14-day postinoculation, but did positively correlate with plasma VLs at days 21 and 28 postinfection.
  
  
  CONCLUSIONS
  The median eclipse time after intrarectal challenge was 7 days, with a few early transmitters at 4 days. More rapid viral dissemination was associated with a high frequency of colorectal Ki67CCR5CD4T cells, which fuel the local viral replication. Furthermore, local viral replication in the colorectal tissue during the early stage might affect the plasma VL in a delayed manner. Therefore, to reduce/limit these target cells at the portal of viral entry is essential.
authors.affiliation: *Vaccine Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD; †Advanced BioScience Laboratories, Inc., Rockville, MD; and ‡Biostatistics and Data Management Section, National Cancer Institute, National Institutes of Health, Bethesda, MD.
authors.forename: Yongjun
authors.initials: Y
authors.lastname: Sui
authors.forename: Eun Mi
authors.initials: EM
authors.lastname: Lee
authors.forename: Yichuan
authors.initials: Y
authors.lastname: Wang
authors.forename: Alison
authors.initials: A
authors.lastname: Hogg
authors.forename: Blake
authors.initials: B
authors.lastname: Frey
authors.forename: David
authors.initials: D
authors.lastname: Venzon
authors.forename: Ranajit
authors.initials: R
authors.lastname: Pal
authors.forename: Jay A
authors.initials: JA
authors.lastname: Berzofsky
mesh_terms: D000818:Animals; D049109:Cell Proliferation; D003106:Colon / Q000166:cytology* / Q000821:virology; D005260:Female; D008253:Macaca mulatta; D008297:Male; D012367:RNA, Viral / Q000097:blood; D012007:Rectum / Q000166:cytology* / Q000821:virology; D016097:Simian Acquired Immunodeficiency Syndrome / Q000821:virology*; D015302:Simian Immunodeficiency Virus; D013601:T-Lymphocytes / Q000145:classification* / Q000502:physiology; D013997:Time Factors; D019562:Viral Load; D014779:Virus Replication / Q000502:physiology*
chemical_list: D012367:RNA, Viral