Abstract
BackgroundCellulose acetate phthalate (CAP) in soluble form blocks coreceptor binding sites on the virus envelope glycoprotein gp120 and elicits gp41 six-helix bundle formation, processes involved in virus inactivation. CAP is not soluble at pH < 5.5, normal for microbicide target sites. Therefore, the interaction between insoluble micronized CAP and HIV-1 was studied. Carbomer 974P/BufferGel; carrageenan; cellulose sulfate; dextran/dextrin sulfate, poly(napthalene sulfonate) and poly(styrene-4-sulfonate) are also being considered as anti-HIV-1 microbicides, and their antiviral properties were compared with those of CAP.MethodsEnzyme linked immunosorbent assays (ELISA) were used to (1) study HIV-1 IIIB and BaL binding to micronized CAP; (2) detect virus disintegration; and (3) measure gp41 six-helix bundle formation. Cells containing integrated HIV-1 LTR linked to the β-gal gene and expressing CD4 and coreceptors CXCR4 or CCR5 were used to measure virus infectivity.Results1) HIV-1 IIIB and BaL, respectively, effectively bound to micronized CAP. 2) The interaction between HIV-1 and micronized CAP led to: (a) gp41 six-helix bundle formation; (b) virus disintegration and shedding of envelope glycoproteins; and (c) rapid loss of infectivity. Polymers other than CAP, except Carbomer 974P, elicited gp41 six-helix bundle formation in HIV-1 IIIB but only poly(napthalene sulfonate), in addition to CAP, had this effect on HIV-1 BaL. These polymers differed with respect to their virucidal activities, the differences being more pronounced for HIV-1 BaL.ConclusionsMicronized CAP is the only candidate topical microbicide with the capacity to remove rapidly by adsorption from physiological fluids HIV-1 of both the X4 and R5 biotypes and is likely to prevent virus contact with target cells. The interaction between micronized CAP and HIV-1 leads to rapid virus inactivation. Among other anionic polymers, cellulose sulfate, BufferGel and aryl sulfonates appear most effective in this respect.
Highlights
Cellulose acetate phthalate (CAP) in soluble form blocks coreceptor binding sites on the virus envelope glycoprotein gp120 and elicits gp41 six-helix bundle formation, processes involved in virus inactivation
Effect of anionic polymeric microbicide candidates on the integrity of human immunodeficiency virus type 1 (HIV-1) particles Since micronized CAP caused the dissociation of HIV-1 particles [31]; (Fig. 3), it was of interest to determine whether anionic polymeric candidate microbicides in soluble form at neutral pH would have similar effects
While no such effects were seen with HIV-1 IIIB, the integrity of HIV-1 BaL appeared to be partially diminished by treatment with CAP and drastically affected by cellulose sulfate (Fig. 6)
Summary
Cellulose acetate phthalate (CAP) in soluble form blocks coreceptor binding sites on the virus envelope glycoprotein gp120 and elicits gp six-helix bundle formation, processes involved in virus inactivation. Several anionic polymers were shown to have HIV-1 inhibitory activity and are being considered and evaluated as vaginal topical microbicides for prevention of transmission of sexually transmitted disease (STD) pathogens, including HIV-1 These polymers belong to several classes: (1) sulfate esters of polysaccharides (dextrin and dextran sulfates [1,2,3,4,5,6,7,8,9,10,11]; cellulose sulfate [12,13,14,15]; sulfate esters of (page number not for citation purposes). It is preferable that microbicides irreversibly inactivate the virus upon the first compound/HIV-1 encounter in the vaginal environment, i.e. microbicides should have direct virucidal activity Such activity was reported for dextran sulfate after 2 h incubation with HIV-1 [2] but results of other studies indicated that dextran sulfate failed to neutralize virus infectivity [4,10]. It was of interest to determine how CAP in micronized form and other candidate polymeric microbicides affect X4 and R5 viruses represented by HIV-1 IIIB and BaL, respectively
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
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 callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
