Salivary basic proline-rich proteins are elevated in HIV-exposed seronegative men who have sex with men

Abstract

Innate mucosal factors are associated with protection in HIV-exposed seronegative (HESN) individuals, but studies of MSM have been very limited. We performed proteomic analysis of saliva from a cohort of HESN MSM who have regular unprotected oral receptive intercourse with their HIV-infected partner. Saliva samples from HESN (n = 25) and non-exposed male controls (n = 22) were analyzed by 2D-LC mass spectrometry. An overexpressed innate protein factor was further characterized by immunoblot, and compared with CC-chemokine expression, HIV-neutralizing activity, clinical factors, and sexual behavior. Of 337 total proteins, seven were identified as differentially abundant in the HESN group. The five overabundant proteins (Basic salivary proline-rich proteins (bPRP) 2 and 3, Histatin-3, Lysozyme C, and SLPI) have known antimicrobial activity. bPRP2 showed the highest overabundance (>six-fold) in HESN individuals compared with controls (P = 0.009), including multiple isoforms. Salivary bPRP2 correlated with CC-chemokine levels in HESN individuals including RANTES (P = 0.02), MIP-1-alpha (P = 0.01), MIP-1-beta (P = 0.0002), MCP-1 (P = 0.005) and Eotaxin (P = 0.003) but not with frequency of HIV neutralizing activity, oral sexual practices, or viral load of the sexual partner. This study identifies salivary bPRP2 as a novel soluble factor elevated in the oral compartment of HIV-exposed MSM.