Abstract
During sexual transmission of human immunodeficiency virus (HIV), macrophages are initial targets for HIV infection. Secretory leukocyte protease inhibitor (SLPI) has been shown to protect against HIV infection of macrophages through interactions with annexin A2 (A2), which is found on the macrophage cell surface as a heterotetramer (A2t) consisting of A2 and S100A10. Therefore, we investigated potential protein-protein interactions between A2 and HIV-1 gp120 through a series of co-immunoprecipitation assays and a single molecule pulldown (SiMPull) technique. Additionally, inhibitors of A2t (A2ti) that target the interaction between A2 and S100A10 were tested for their ability to impair productive HIV-1 infection of macrophages. Our data suggest that interactions between HIV-1 gp120 and A2 exist, though this interaction may be indirect. Furthermore, an anti-A2 antibody impaired HIV-1 particle production in macrophages in vitro, whereas A2ti did not indicating that annexin A2 may promote HIV-1 infection of macrophages in its monomeric rather than tetrameric form.
Highlights
During sexual transmission of human immunodeficiency virus (HIV), macrophages of the cervical, anal, and foreskin epithelium are among the first immune cells to encounter the virus, which makes them initial targets for HIV infection [1, 2]
Through a series of enzyme-linked immunosorbent assays (ELISA) and co-immunoprecipitation assays, we investigated whether Annexin A2 (A2) directly interacts with the primary HIV-1 envelope protein gp120
Following published procedures that we utilized for the evaluation of A2 interactions with Human papillomavirus type 16 (HPV16) [18], we found that recombinant gp120 was not able to bind to purified A2 or S100A10 when measured via ELISA, and that gp120 incubated with macrophages was unable to co-IP with A2
Summary
During sexual transmission of human immunodeficiency virus (HIV), macrophages of the cervical, anal, and foreskin epithelium are among the first immune cells to encounter the virus, which makes them initial targets for HIV infection [1, 2]. HIV-1 infects macrophages through the canonical CD4 receptor CCR5 coreceptor pathway [2, 9], though numerous cofactors can affect the efficiency of this process and the rate of infection [5, 6]. Entry inhibitors, such as the CCR5 antagonist maraviroc [10], often lead to the emergence of resistant HIV-1 strains that can use alternative pathways [9]. Alternative pathways of HIV-1 infection are likely to differ in macrophages and CD4+ T cells as they express different membrane
Sign-in/Register to view highlights & summary 
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call