title: Salivary agglutinin inhibits HIV type 1 infectivity through interaction with viral glycoprotein 120.
abstract: Salivary agglutinin (SAG) is a high molecular mass glycoprotein (340 kDa) that plays important roles in innate immunity. SAG has been found to specifically inhibit HIV-1 infectivity and to bind to virus through the envelope protein gp120. Although SAG binds to gp120 of the virus, the exact nature of this binding has not been characterized. Using surface plasmon resonance technology, we have found that SAG interacts with recombinant envelopes derived from diverse HIV-1 isolates with K(D) values ranging from 10(-7) to 10(-10) M, comparable to gp120-sCD4 binding. Furthermore, SAG binding to gp120 is Ca(2+) dependent. sCD4 prebound to gp120 failed to abrogate SAG binding, suggesting a distinct mechanism for SAG inhibition of HIV-1 infectivity. Inhibition by monoclonal antibodies specific for carbohydrates also implicates the involvement of carbohydrates in the interaction between SAG and gp120. These results argue that the anti-HIV-1 activity of SAG is due to carbohydrate-mediated binding to gp120. A demonstration that SAG is related to lung scavenger receptor, gp-340, further suggests the roles of SAG in preventing pathogen invasion at the entry portal and raises its potential as an anti-HIV-1 drug candidate.
authors.affiliation: Department of Biochemistry, School of Dental Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Zhiwei
authors.initials: Z
authors.lastname: Wu
authors.forename: Donald
authors.initials: D
authors.lastname: Van Ryk
authors.forename: Cheryl
authors.initials: C
authors.lastname: Davis
authors.forename: William R
authors.initials: WR
authors.lastname: Abrams
authors.forename: Irwin
authors.initials: I
authors.lastname: Chaiken
authors.forename: John
authors.initials: J
authors.lastname: Magnani
authors.forename: Daniel
authors.initials: D
authors.lastname: Malamud
mesh_terms: D000373:Agglutinins / Q000276:immunology / Q000494:pharmacology*; D000911:Antibodies, Monoclonal / Q000276:immunology; D001665:Binding Sites; D002118:Calcium / Q000378:metabolism; D018929:Cell Culture Techniques; D015699:HIV Envelope Protein gp120 / Q000276:immunology / Q000378:metabolism*; D015497:HIV-1 / Q000737:chemistry / Q000187:drug effects*; D006801:Humans; D012469:Salivary Glands / Q000737:chemistry*
chemical_list: D000373:Agglutinins; D000911:Antibodies, Monoclonal; D015699:HIV Envelope Protein gp120; D002118:Calcium