Anti-HIV-1 activity of anionic polymers: a comparative study of candidate microbicides.
BACKGROUND
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. 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.


METHODS
Enzyme 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 beta-gal gene and expressing CD4 and coreceptors CXCR4 or CCR5 were used to measure virus infectivity.


RESULTS
1) 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.


CONCLUSIONS
Micronized 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.
Neurath
A Robert
AR
Biochemical Virology Laboratory, The Lindsley F, Kimball Research Institute of the New York Blood Center, New York, NY 10021, USA. arneurath@worldnet.att.net
Strick
Nathan
N
Li
Yun-Yao
YY
D000180:Acrylic Resins; D019380:Anti-HIV Agents / Q000494:pharmacology*; D001777:Blood Coagulation / Q000187:drug effects; D002351:Carrageenan / Q000494:pharmacology; D002478:Cells, Cultured; D002482:Cellulose / Q000031:analogs & derivatives* / Q000494:pharmacology; D016264:Dextran Sulfate / Q000494:pharmacology; D003911:Dextrans / Q000494:pharmacology; D015700:HIV Envelope Protein gp41 / Q000737:chemistry; D015497:HIV-1 / Q000187:drug effects*; D006801:Humans; D008826:Microbial Sensitivity Tests; D017433:Protein Structure, Secondary / Q000187:drug effects; D013089:Spermatocidal Agents / Q000494:pharmacology
D000180:Acrylic Resins; D019380:Anti-HIV Agents; C420918:BufferGel; D003911:Dextrans; D015700:HIV Envelope Protein gp41; D013089:Spermatocidal Agents; D002351:Carrageenan; D002482:Cellulose; C020254:cellulose sulfate; D016264:Dextran Sulfate