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.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3023938 | PMC |
| http://dx.doi.org/10.1016/j.chom.2010.11.003 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
APOBEC-1 cofactors regulate APOBEC3-induced mutations in hepatitis B virus.
J Virol
January 2025
Department of Laboratory Medicine, Clinical Center, National Institutes of Health, Bethesda, Maryland, USA.
Unlabelled: APOBEC3 proteins (A3s) play an important role in host innate immunity against viruses and DNA mutations in cancer. A3s-induced mutations in both viral and human DNA genomes vary significantly from non-lethal mutations in viruses to localized hypermutations, such as kataegis in cancer. How A3s are regulated remains largely unknown.
View Article and Find Full Text PDFImpact of APOBEC3s on the occurrence, development and prognosis of esophageal squamous cell carcinoma.
Future Oncol
January 2025
Department of Oncology, Daping Hospital, Army Medical University, Chongqing, China.
Esophageal squamous cell carcinoma (ESCC) is a severe malignant tumor of the digestive system that poses a significant threat to human health. Despite its significance, the complex molecular mechanism regulating the occurrence and development of ESCC remain elusive. The apolipoprotein B mRNA editing enzyme catalytic polypeptide-like 3 (APOBEC3) members constitute a pivotal subfamily of the APOBEC family that possess cytidine deaminase activity.
View Article and Find Full Text PDFThe unique structure of the highly conserved PPLP region in HIV-1 Vif is critical for the formation of APOBEC3 recognition interfaces.
mBio
January 2025
Department of Infectious Diseases and Immunology, Clinical Research Center, National Hospital Organization Nagoya Medical Center, Nagoya, Aichi, Japan.
The human cellular cytidine deaminases APOBEC3s (A3s) inhibit virion infectivity factor (Vif)-deficient HIV-1 replication. However, virus-encoded Vifs abolish this defense system by specifically recruiting A3s to an E3 ubiquitin ligase complex to induce their degradation. The highly conserved Vif PPLP motif is critical for the Vif-mediated antagonism of A3s and is believed to be important for Vif multimerization.
View Article and Find Full Text PDFA simple phylogenetic approach to analyze hypermutated HIV proviruses reveals insights into their dynamics and persistence during antiretroviral therapy.
Virus Evol
November 2024
Faculty of Health Sciences, Simon Fraser University, 8888 University Drive, Burnaby, BC V5A 1S6, Canada.
Hypermutated proviruses, which arise in a single Human Immunodeficiency Virus (HIV) replication cycle when host antiviral APOBEC3 proteins introduce extensive guanine to adenine mutations throughout the viral genome, persist in all people living with HIV receiving antiretroviral therapy (ART). However, hypermutated sequences are routinely excluded from phylogenetic trees because their extensive mutations complicate phylogenetic inference, and as a result, we know relatively little about their within-host evolutionary origins and dynamics. Using >1400 longitudinal single-genome-amplified HIV sequences isolated from six women over a median of 18 years of follow-up-including plasma HIV RNA sequences collected over a median of 9 years between seroconversion and ART initiation, and >500 proviruses isolated over a median of 9 years on ART-we evaluated three approaches for masking hypermutation in nucleotide alignments.
View Article and Find Full Text PDFUntargeted Mutation Triggered by Ribonucleoside Embedded in DNA.
Int J Mol Sci
December 2024
Graduate School of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8553, Japan.
DNA polymerases frequently misincorporate ribonucleoside 5'-triphosphates into nascent DNA strands. This study examined the effects of an incorporated ribonucleoside on untargeted mutations in human cells. Riboguanosine (rG) was introduced into the downstream region of the gene to preferentially detect the untargeted mutations.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!