[PMC free article] [PubMed] [Google Scholar]Savilahti EM, Kukkonen AK, Kuitunen M, Savilahti E. oral transmission of HIV through adult oropharyngeal mucosal epithelium is rare: The infection rate per oral sexual exposure is estimated to be 0.00C0.04% (Page-Shafer et al., 2006; Tudor-Williams and Lyall, 1999; UNAIDS, 2011). In contrast, mother-to-child transmission (MTCT) of HIV through fetal/neonatal oral and gastrointestinal epithelia is much more common. Without intervention, Rabbit polyclonal to APE1 the rate of MTCT can reach 30C45% (Boyle et al., 2013; Lehman and Farquhar, 2007; UNAIDS, 2013; Wood et al., 2013). Likewise, HIV transmission is about 10 times more frequent through cervicovaginal epithelium than through adult oral epithelium (Anderson et al.; Baggaley et al., 2013; Baggaley et al., 2010; Campo et al., 2006; Pope and Haase, 2003; Rothenberg et al., 1998; Scully and Porter, 2000; Younai, 2001), and HIV transmission through anal sex is estimated to be 18 times higher than the risk through vaginal sex (Baggaley et al., 2013; Baggaley et al., 2010; Boily et al., 2009a; Boily et al., 2009b). Although the variability of HIV transmission through different mucosal epithelial sites is well Estropipate documented, very little Estropipate is known about the role of epithelial-specific biological factors, including that of innate immune proteins, in the modulation of transepithelial transmission of virus. Mucosal epithelia express multiple epithelial-specific anti-HIV innate immune proteins, including human beta-defensins 2 (hBD2), hBD3, and secretory leukocyte protease inhibitor (SLPI), which may reduce viral mucosal transmission (Borrow et al., 2010; Jana et al., 2005; Ma et al., 2004; McNeely et al., 1997; Sun et al., 2005; Wahl et al., 1997; Wang et al., 2003; Wang et al., 2004; Weinberg et al., 2011; Weinberg et al., 2006). However, expression of anti-viral innate proteins may vary in mucosal epithelia at different geographic sites and could depend on age. For example, adult oral mucosa constitutively expresses high levels of hBD2, hBD3, and SLPI, but expression of these innate proteins in fetal and Estropipate infant oral epithelium is very low (Dale et al., 2001; Dunsche et al., 2002; Jana et al., 2005; Moutsopoulos et al., 2007; Quinones-Mateu et al., 2003; Sun et al., 2005; Tugizov et al., 2011). Expression of hBD2, hBD3, and SLPI in the genital mucosa is not stable and depends on the menstrual cycle; i.e., hBD3 and SLPI are expressed during the secretory phase, and hBD2 has been detected only during menstruation (King Estropipate et al., 2003; Moriyama et al., 1999). Expression of hBD2, hBD3 and SLPI in established polarized cervical epithelial cells is barely detectable (Tugizov et al., 2011). There are higher levels of innate protein expression in saliva than in rectal fluid, as shown by comparative proteomic analysis (Romas et al., 2014). Defensins are small, 3- to 5-kDa cysteine-rich cationic innate proteins with a broad spectrum of antimicrobial and antiviral properties (Dhople et al., 2006; Schroder and Harder, 1999). The anti-HIV functions of hBD2 and hBD3 have been investigated in both X4- and Estropipate R5-tropic viruses (Sun et al., 2005; Wang et al., 2003; Wang et al., 2004; Weinberg et al., 2006). These defensins bind to the HIV envelope and inactivate both X4- and R5-tropic viruses (Quinones-Mateu et al., 2003; Sun et al., 2005; Wang et al., 2003; Wang et al., 2004; Weinberg et al., 2006). hBD2 and hBD3 downregulate C-X-C chemokine receptor type 4 and inhibit entry of X4-tropic HIV-1 (Quinones-Mateu et al., 2003). hBD2 and hBD3 also inhibit HIV replication at an early stage by reducing reverse transcription activity of the virus (Sun et al., 2005). Although the anti-HIV activity of hBD2 and hBD3 has been investigated in HIV-susceptible CD4+ T lymphocytes and peripheral blood mononuclear cells (PBMC), the molecular mechanisms of antiviral functions of defensins in mucosal epithelial cells, the.