RETROVIRUS INFECTION OF ENTEROCYTES

Abstract

SummaryAlthough the gastrointestinal tract is thought to be one of the major routes for infection with human immunodeficiency virus (HIV), controversy still exists concerning the ability of HIV to infect epithelial cells of the intestinal mucosa. In this paper, Fantini et al. detailed their studies of the ability of HIV to infect the human colon cancer cell line HT‐29‐D4. Differentiation of these epithelial cells can be regulated in vitro by modifying the culture medium concentration of glucose and by replacing glucose with galactose. Intestinal cells in culture were infected with three different strains of HIV—HIV‐1‐BRU, HIV‐1‐NDK (a highly cytopathic strain), and HIV‐2‐ROD. Exponentially growing HT‐29‐D4 cells were exposed for 16 h to HIV in serum‐supplemented medium. After washing, epithelial cells were harvested and subcultured. Virus replication in subcultured cells was determined by HIV‐specific DNA amplification using the polymerase chain reaction. Amplified products were analyzed for specificity by Southern blot hybridization with a radiolabeled DNA probe internal to the primer templates. The presence of CD4 molecules (i.e., receptors for cell binding of HIV) on intestinal epithelial cells was assessed using monoclonal antibodies and immunofluorescence labeling.Fantini et al. found that undifferentiated HT‐29‐D4 cells express a CD4‐related antigen that lacks the epitope known to be involved in recognition of the HIV envelope binding protein referred to as gp120. Undifferentiated HT‐29‐D4 cells were infected by both HIV‐1 and HIV‐2 strains. However, the infection did not alter cell growth. Differentiated HT‐29‐D4 cells were also infected, either through the apical brush border or the basolateral membrane. Although the CD4‐like surface molecules were restricted to the basolateral domain of differentiated cells, antibodies against specific epitopes of the CD4 glycoprotein did not inhibit HIV infection. The authors conclude that intestinal epithelial cells can be infected by both HIV‐1 and HIV‐2 via either the apical membrane or the basolateral membrane. There was no evidence of viral replication by reverse transcriptase activity. However, following culture of HT‐29‐D4 cells with virus, HIV DNA could be recovered by gene amplification as long as 9 months after exposure of intestinal tissue culture cells to the virus. The authors speculate that this might provide an explanation for the prolonged seronegative state observed in HIV‐infected individuals.These findings raise the possibility that infected lamina propria lymphocytes and macrophages could coinfect intestinal epithelial cells. In addition, HIV present in the intestinal lumen could bind to the apical surface and infect enterocytes.