The female reproductive tract (FRT) is a major site of HIV sexual transmission. 
As the outermost layer of cells in the FRT, the human cervical epithelial cells 
(HCEs) have direct contact with HIV or infected cells. Our early work showed 
that supernatant (SN) from TLR3-activated HCEs contain the antiviral factors 
that could potently inhibit HIV replication in macrophages. However, it remains 
to be determined how HCEs transport the anti-HIV factors to macrophages. This 
follow-up study examined the role of exosomes in HCE-mediated anti-HIV activity. 
We found that TLR3 activation of HCEs resulted in the release of exosomes that 
contained multiple IFN-stimulated genes (ISGs: ISG56, OAS1, MxA, and Mx2) and 
the HIV restriction microRNAs (miR-28, miR-29 family members, miR-125b, miR-150, 
miR-382, miR-223, miR-20a, and miR-198). The depletion of exosomes from SN of 
TLR3-activated HCEs diminished HCE-mediated anti-HIV activity in macrophages, 
indicating that HCE-derived exosomes are responsible for transporting the 
antiviral molecules to macrophages. These in vitro findings suggest a novel 
antiviral mechanism by which HCEs participate in the FRT innate immunity against 
HIV infection. Further in vivo studies are necessary in order to develop an 
exosome-based delivery system for prevention and treatment of HIV infection 
through sexual transmission.