Primary human mammary epithelial cells endocytose HIV-1 and facilitate viral infection of CD4+ T lymphocytes.
The contribution of mammary epithelial cells (MEC) to human immunodeficiency virus type 1 (HIV-1) in breast milk remains largely unknown. While breast milk contains CD4(+) cells throughout the breast-feeding period, it is not known whether MEC directly support HIV-1 infection or facilitate infection of CD4(+) cells in the breast compartment. This study evaluated primary human MEC for direct infection with HIV-1 and for indirect transfer of infection to CD4(+) target cells. Primary human MEC were isolated and assessed for expression of HIV-1 receptors. MEC were exposed to CCR5-, CXCR4- and dual-tropic strains of HIV-1 and evaluated for viral reverse transcription and integration and productive viral infection. MEC were also tested for the ability to transfer HIV to CD4(+) target cells and to activate resting CD4(+) T cells. Our results demonstrate that MEC express HIV-1 receptor proteins CD4, CCR5, CXCR4, and galactosyl ceramide (GalCer). While no evidence for direct infection of MEC was found, HIV-1 virions were observed in MEC endosomal compartments. Coculture of HIV-exposed MEC resulted in productive infection of activated CD4(+) T cells. In addition, MEC secretions increased HIV-1 replication and proliferation of infected target cells. Overall, our results indicate that MEC are capable of endosomal uptake of HIV-1 and can facilitate virus infection and replication in CD4(+) target cells. These findings suggest that MEC may serve as a viral reservoir for HIV-1 and may enhance infection of CD4(+) T lymphocytes in vivo.
Dorosko
Stephanie M
SM
Department of Microbiology and Immunology, Dartmouth Medical School, 1 Medical Center Drive, HB 7556, Lebanon, NH 03756, USA. Stephanie.M.Dorosko@Dartmouth.edu
Connor
Ruth I
RI
D001483:Base Sequence; D001940:Breast / Q000166:cytology / Q000276:immunology* / Q000821:virology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000821:virology*; D002478:Cells, Cultured; D018920:Coculture Techniques; D004279:DNA, Viral / Q000235:genetics; D004197:Disease Reservoirs / Q000821:virology; D004705:Endocytosis; D004847:Epithelial Cells / Q000276:immunology / Q000648:ultrastructure / Q000821:virology; D005260:Female; D005699:Galactosylceramides / Q000378:metabolism; D015658:HIV Infections / Q000209:etiology* / Q000276:immunology / Q000635:transmission / Q000821:virology; D015497:HIV-1 / Q000235:genetics / Q000276:immunology* / Q000472:pathogenicity* / Q000502:physiology; D006801:Humans; D008213:Lymphocyte Activation; D046529:Microscopy, Electron, Transmission; D019713:Receptors, CCR5 / Q000378:metabolism; D019718:Receptors, CXCR4 / Q000378:metabolism; D015728:Receptors, HIV / Q000378:metabolism; D014779:Virus Replication
C527276:CXCR4 protein, human; D004279:DNA, Viral; D005699:Galactosylceramides; D019713:Receptors, CCR5; D019718:Receptors, CXCR4; D015728:Receptors, HIV