PRODUCTIVE HIV-1 INFECTION OF NORMAL HUMAN MAMMARY EPITHELIAL-CELLS

Objective and design: To determine the susceptibility of mammary epith elial cells (MEG) to HIV-1 as breastfeeding is an established route of HIV transmission, although the origin of virus in breastmilk is uncle ar. Methods: Primary epithelial cell cultures were derived from the ma mmary glands of healthy donors; immortalized MEC lines were also used. HIV infection was followed by detection of infectious particle produc tion, p24 antigen and viral sequences. Results: Seven out of 11 primar y MEC cultures and two out of three MEC lines were productively infect ed by HIV-1. Virus replication significantly reduced cell proliferatio n, although cell viability was only slightly affected. Cytopathic chan ges were not observed. MEC cultures expressed low levels of surface CD 4, galactosylceramide and CD26, but essentially no human leukocyte ant igen (HLA)-DR. Infection of HIV-permissive MEC cells was associated wi th the upregulation of surface HLA-DR and CD26. In contrast, the expre ssion of CD4, tissue-specific markers, adhesion molecules and growth-f actor receptors was downregulated. To a lesser extent, similar effects were also observed in non-permissive cells. Hormones (triiodothyronin e plus beta-estradiol and prolactin) enhanced HIV replication, possibl y through the stimulation of cellular DNA synthesis. Conclusions: We c oncluded that HIV-1 replication in ductal/alveolar MEC may be, in part , responsible for the presence of HIV-1 in milk; that hormones may sti mulate virus replication; and that infection reduces the growth of epi thelial cells. Although in vitro HIV is produced by MEC to a lesser ex tent than lymphoid cells, MEG-derived HIV might have selective advanta ges for the infection of mucosal epithelial cells during breastfeeding .