title: APOBEC3 proteins expressed in mammary epithelial cells are packaged into retroviruses and can restrict transmission of milk-borne virions.
abstract: Viruses, including retroviruses like human immunodeficiency virus (HIV) and mouse mammary tumor virus (MMTV), are transmitted from mother to infants through milk. Lymphoid cells and antibodies are thought to provide mammary gland and milk-borne immunity. In contrast, little is known about the role of mammary epithelial cells (MECs). The APOBEC3 family of retroviral restriction factors is highly expressed in macrophages and lymphoid and dendritic cells. We now show that APOBEC3 proteins are also expressed in mouse and human MECs. Lymphoid cell-expressed APOBEC3 restricts in vivo spread of MMTV to lymphoid and mammary tissue. In contrast, mammary gland-expressed APOBEC3 is packaged into MMTV virions and decreases the infectivity of milk-borne viruses. Moreover, APOBEC3G and other APOBEC3 genes are expressed in human mammary cells and have the potential to restrict viruses produced in this cell type. These data point to a role for APOBEC3 proteins in limiting infectivity of milk-transmitted viruses.
authors.affiliation: Department of Microbiology and Abramson Cancer Center, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.
authors.forename: Chioma M
authors.initials: CM
authors.lastname: Okeoma
authors.forename: Alyssa L
authors.initials: AL
authors.lastname: Huegel
authors.forename: Jaisri
authors.initials: J
authors.lastname: Lingappa
authors.forename: Michael D
authors.initials: MD
authors.lastname: Feldman
authors.forename: Susan R
authors.initials: SR
authors.lastname: Ross
mesh_terms: D000071478:APOBEC Deaminases; D000818:Animals; D002478:Cells, Cultured; D003564:Cytidine Deaminase / Q000096:biosynthesis / Q000502:physiology*; D043525:Cytosine Deaminase / Q000096:biosynthesis / Q000502:physiology; D004847:Epithelial Cells / Q000378:metabolism* / Q000821:virology; D005260:Female; D015497:HIV-1 / Q000472:pathogenicity; D006801:Humans; D018445:Infectious Disease Transmission, Vertical; D008214:Lymphocytes / Q000378:metabolism; D008321:Mammary Glands, Animal / Q000378:metabolism* / Q000821:virology; D042361:Mammary Glands, Human / Q000378:metabolism* / Q000821:virology; D008324:Mammary Tumor Virus, Mouse / Q000472:pathogenicity / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008892:Milk / Q000821:virology*; D009374:Neoplasms, Experimental / Q000378:metabolism / Q000821:virology; D012192:Retroviridae Infections / Q000378:metabolism* / Q000635:transmission / Q000821:virology; D014412:Tumor Virus Infections / Q000378:metabolism / Q000635:transmission / Q000821:virology; D014771:Virion / Q000502:physiology; D019065:Virus Assembly; D054320:vif Gene Products, Human Immunodeficiency Virus / Q000502:physiology
chemical_list: D054320:vif Gene Products, Human Immunodeficiency Virus; C514847:vif protein, Human immunodeficiency virus 1; D043525:Cytosine Deaminase; D000071478:APOBEC Deaminases; C502889:APOBEC3 proteins, human; C503504:Apobec3 protein, mouse; D003564:Cytidine Deaminase