Surfactant Protein A Binds to HIV and Inhibits Direct Infection of CD4+ Cells, but Enhances Dendritic Cell-Mediated Viral Transfer

Abstract

The identification of surfactant protein A (SP-A) as an important innate immune factor of the lungs, amniotic fluid, and the vaginal tract suggests that it could play an important role during various stages of HIV disease progression and transmission. Therefore, we examined whether SP-A could bind to HIV and also had any effect on viral infectivity. Our data demonstrate that SP-A binds to HIV in a calcium-dependent manner that is inhibitable by mannose and EDTA. Affinity capture of the HIV viral lysate reveals that SP-A targets the envelope glycoprotein of HIV (gp120), which was confirmed by ELISA using recombinant gp120. Digestion of gp120 with endoglycosidase H abrogates the binding of SP-A, indicating that the high mannose structures on gp120 are the target of the collectin. Infectivity studies reveal that SP-A inhibits the infection of CD4+ T cells by two strains of HIV (BaL, IIIB) by >80%. Competition assays with CD4 and mAbs F105 and b12 suggest that SP-A inhibits infectivity by occlusion of the CD4-binding site. Studies with dendritic cells (DCs) demonstrate that SP-A enhances the binding of gp120 to DCs, the uptake of viral particles, and the transfer of virus from DCs to CD4+ T cells by >5-fold at a pH representative of the vaginal tract. Collectively, these results suggest that SP-A acts as a dual modulator of HIV infection by protecting CD4+ T cells from direct infection but enhancing the transfer of infection to CD4+ T cells mediated by DCs.

Carbohydrate-functionalized nanovaccines preserve HIV-1 antigen stability and activate antigen presenting cells

“…Purified protein was finally dialyzed in PBS (pH 8). The endotoxin content in gp41-54Q–GHC was quantified using a commercially available QCL-1000 Limulus Amebocyte Lysate (LAL) kit (Lonza, Switzerland) and found to be <0.1pg/µg of protein, which is acceptable for use in cell-based assays [36–38] for subunit proteins.…”

Synthesis of β-arabinofuranoside glycolipids, studies of their binding to surfactant protein-A and effect on sliding motilities of M. smegmatis

“…SP-A has a bouquet structure of six trimers and possesses molecular weight in the range of 26-38 kDa [14]. SP-A is known to bind pathogens, such as, HIV and mycobacterium by interacting with oligosaccharide glycolipids present on the cell surfaces [15][16][17]. The binding studies of SP-A with the polysaccharide glycolipids extracted from mycobacterial cell wall components were studied in detail, with the aid of SPR technique [2].…”

Secreted Mucosal Antimicrobials in the Female Reproductive Tract that are Important to Consider forHIVPrevention

“…13, 45 Some endogenous antimicrobials, such as surfactants, are lectin-like molecules [46][47][48] or glycoproteins (e.g., thrombospondin). 49 Lectins are a class of pattern recognition molecules that are chemotactic, and several surfactants, for example, surfactants A and D, are present in the FRT and have been shown to have anti-HIV functions.…”

“…49 Lectins are a class of pattern recognition molecules that are chemotactic, and several surfactants, for example, surfactants A and D, are present in the FRT and have been shown to have anti-HIV functions. 46,47,50,51 Another class of FRT molecules that can have pathogen-inhibiting functions is mucin. Mucins are the predominant component of mucus, a thick viscous fluid that covers all mucosal surfaces and acts as a protective barrier against invading pathogens.…”