       Document 0158
 DOCN  M9490158
 TI    HIV infection of human fetal intestinal explant cultures induces
       epithelial cell proliferation.
 DT    9411
 AU    Batman PA; Fleming SC; Sedgwick PM; MacDonald TT; Griffin GE; Department
       of Histopathology, Bradford Royal Infirmary, UK.
 SO    AIDS. 1994 Feb;8(2):161-7. Unique Identifier : AIDSLINE MED/94318199
 AB    OBJECTIVE: The concept that HIV infection per se alters small intestinal
       mucosal structure and function (HIV enteropathy) remains controversial
       and in this study we report in vitro experiments designed to elucidate
       the matter. METHODS: Twenty pairs of human fetal intestinal tissue
       explants were maintained in vitro for up to 14 days; one explant of each
       pair was incubated and infected with HIV, and the other served as a
       matched uninfected control. At various times after infection, explant
       culture fluid and tissue were removed, p24 concentration was measured
       and tissue formalin fixed. Explant tissue was embedded in paraffin wax
       and sections stained by an immunoperoxidase method directed against
       proliferating cell nuclear antigen (PCNA). The percentage of
       proliferating crypt and villous epithelial cells, stained by PCNA, was
       calculated in paired samples. The difference between the percentage for
       paired samples was designated delta crypt proliferation (delta CP) and
       delta villous proliferation (delta VP), respectively. Epithelial cell
       proliferation was deemed to be enhanced if the percentage of
       PCNA-stained cells was greater in the HIV-infected than in the control
       tissue. RESULTS: Explant culture fluid from tissue exposed to HIV showed
       a progressive rise in p24 antigen (Ag) level, indicating HIV infection
       of these explants. Fifteen pairs of explants showed progressively
       positive delta CP with time (P < 0.01) indicating crypt hyperplasia and
       all 20 pairs of explants showed positive delta VP, indicating
       hyperplasia of villous epithelial cells. CONCLUSIONS: This study
       provides direct evidence that HIV stimulates epithelial cell
       proliferation in intestinal mucosa. HIV-infected human intestinal
       explants provide a model of crypt hyperplastic villous atrophy
       previously described as HIV enteropathy and detected in clinical biopsy
       specimens from HIV-infected patients.
 DE    Atrophy  Biological Markers  Cell Division
       Epithelium/MICROBIOLOGY/PATHOLOGY  Human  Hyperplasia  HIV Core Protein
       p24/ANALYSIS  HIV-1/*PHYSIOLOGY  Intestinal
       Mucosa/EMBRYOLOGY/*MICROBIOLOGY/PATHOLOGY  Nuclear Proteins/ANALYSIS
       Organ Culture  Support, Non-U.S. Gov't  JOURNAL ARTICLE

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).

