Comparison of Human Immunodeficiency Virus Type 1-Specific Inhibitory Activities in Saliva and Other Human Mucosal Fluids

Abstract

Several human mucosal fluids are known to possess an innate ability to inhibit human immunodeficiency virus type 1 (HIV-1) infection and replication in vitro. This study compared the HIV-1 inhibitory activities of several mucosal fluids, whole, submandibular/sublingual (sm/sl), and parotid saliva, breast milk, colostrum, seminal plasma, and cervicovaginal secretions, from HIV-1-seronegative donors by using a 3-day microtiter infection assay. A wide range of HIV-1 inhibitory activity was exhibited in all mucosal fluids tested, with some donors exhibiting high levels of activity while others showed significantly lower levels. Colostrum, whole milk, and whole saliva possessed the highest levels of anti-HIV-1 activity, seminal fluid, cervicovaginal secretions, and sm/sl exhibited moderate levels, and parotid saliva consistently demonstrated the lowest levels of HIV-1 inhibition. Fast protein liquid chromatography gel filtration studies revealed the presence of at least three distinct peaks of inhibitory activity against HIV-1 in saliva and breast milk. Incubation of unfractionated and fractionated whole saliva with antibodies raised against human lactoferrin (hLf), secretory leukocyte protease inhibitor (SLPI), and, to a lesser extent, MG2 (high-molecular-weight mucinous glycoprotein) reduced the HIV-1 inhibitory activity significantly. The results suggest that hLf and SLPI are two key components responsible for HIV-1 inhibitory activity in different mucosal secretions. The variation in HIV inhibitory activity between the fluids and between individuals suggests that there may be major differences in susceptibility to HIV infection depending both on the individual and on the mucosal fluid involved.

Association of HIV-1 Envelope-Specific Breast Milk IgA Responses with Reduced Risk of Postnatal Mother-to-Child Transmission of HIV-1

“…To investigate if maternal neutralization responses were associated with postnatal transmission in our study cohort, we assessed the HIV-1 neutralization activity of breast milk from transmitting and nontransmitting mothers using the TZM-bl HIV-1 neutralization assay. Milk from HIV-1-uninfected women was included to define the low, innate background levels of neutralization commonly observed with breast milk and other mucosal samples (8,34,35). We found that the milk from transmitting and nontransmitting women had higher neutralization activities against the tier 1 clade-matched isolate C.MW965 than those observed in uninfected control women (Fig.…”

Human Seminal Plasma Abrogates the Capture and Transmission of Human Immunodeficiency Virus Type 1 to CD4 + T Cells Mediated by DC-SIGN

“…By analyzing samples of cervicovaginal fluids, these authors found that 12.6% of these samples were able to inhibit the interaction of HIV-1 to B-THP-1-DC-SIGN cells and that the inhibitory activity is mediated by a highmolecular-weight glycoprotein. Endogenous anti-HIV-1 activity has been also demonstrated in whole, parotid, and submandibular/sublingual saliva, with lactoferrin, secretory leukocyte protease, and high-molecular-weight mucinous glycoprotein being the three major compounds responsible for this effect (26). Another natural HIV-1 inhibitor was recently described by Munch et al (36).…”

Tenascin-C is an innate broad-spectrum, HIV-1–neutralizing protein in breast milk

“…In addition, a recent study reported an association between the prevalence of certain oligosaccharides in milk and the risk of infant HIV-1 acquisition (16), potentially explained by the ability of oligosaccharides to prevent HIV-1 virion interaction with dendritic cells (17,18). However, a previous report of the HIV-1-inhibitory properties of mucosal fluids noted that the majority of the HIVneutralizing activity of milk was solely contained in the high molecular mass protein fraction (>500 kDa), which would not be accounted for by previously identified HIV-1-neutralizing factors in breast milk (7). Thus, the primary, high molecular mass HIV-1-neutralizing factor in breast milk remains to be identified, and identification of this factor may inform immunologic strategies to prevent postnatal HIV-1 transmission.…”