Intestinal Epithelium Selectively Transfers R5 HIV-1 to Target Cells -- HIV/AIDS INFO AND UPDATES

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Date Posted: 22:08:33 02/28/02 Thu
Author: Anonymous
Subject: Intestinal Epithelium Selectively Transfers R5 HIV-1 to Target Cells

Intestinal Epithelium Selectively Transfers R5 HIV-1 to Target Cells

NEW YORK (Reuters Health) Feb 18 - Because primary intestinal epithelial cells (IECs) express the CCR5 but not the CXCR4 coreceptor for HIV, they selectively transfer R5 HIV to target cells. According to investigators, this may explain why HIV transmitted vertically or by oral-genital contact is almost always R5 type.

Dr. Phillip D. Smith, of the University of Alabama at Birmingham, and colleagues isolated a mixture of villus and crypt epithelial cells by using protease digestion of human jejunal mucosa. CXCR4 was not expressed on the epithelial cells, but the alternative primary HIV-1 receptor galactosylceramide (GalCer) and CCR5 were expressed there. The authors confirmed this finding using intestinal epithelial cells from 6 individual donors.

As described in the February issue of Nature Medicine, the researchers exposed IECs to an R5 virus, and then co-incubated the IECs with indicator cells derived from HeLa cells. This resulted in infection of the indicator cells. This infection did not take place after the IEC exposure to an X4 virus. Preincubating the IECs with anti-GalCer reduced the transfer of the R5 virus.

Dr. Smith's team further showed that uptake and transfer of virus did not involve virus-IEC fusion. Instead, as demonstrated when temperature was reduced to 4 degrees C, the indicator cells did not become infected, indicating that IEC transfers HIV using a transcytosis mechanisms. Only viable IECs in contact with indicator cells could transfer the virus.

In the investigative team's next experiment, IECs were pretreated with colchicine, which depolymerizes microtubules. Infection of the indicator cells was prevented, which led the investigators to suggest that viral transfer occurs primarily through an intracellular mechanism involving microtubule-mediated transcytosis.

"Virus transcytosed to the basolateral surface of the IEC seems to be delivered via exocytosis to an interdigitating CCR5+ cell in a cell contact-dependent manner," the researchers conclude.

Nature Med 2002;8:150-156.

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Reuters Health Information 2002. � 2002 Reuters Ltd
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