Words similar to coreceptors
Example sentences for: coreceptors
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Cellulose acetate phthalate (CAP) is a promising microbicide candidate for prevention of infection by sexually transmitted disease (STD) pathogens, including HIV-1 [ 1 2 3 4 5 6 7 ] . CAP inactivates HIV-1 and blocks the coreceptor binding site on the virus envelope glycoprotein gp120, while leaving the site for the primary cellular receptor CD4 accessible [ 8 9 ] Soluble CD4 (sCD4) was shown to inhibit HIV-1 infection by two mechanisms: reversible blockage of virus binding to receptors, and irreversible inactivation of virus infectivity [ 10 ] . Since CAP and sCD4 bind to distinct domains on the HIV-1 envelope, it was of interest to determine whether or not these two ligands affect virus infectivity synergistically as do other combinations of anti-HIV-1 drugs and sCD4 [ 11 12 ] Binding of sCD4 leads to conformational changes in gp120 [ 13 14 15 16 17 ] . Binding of gp120 to coreceptors CXCR4 and CCR5, respectively, triggers additional conformational changes in HIV-1 envelope glycoproteins [ 18 19 ] For these reasons it was of interest to determine whether a) pretreatment of HIV-1 with sCD4 would affect subsequent binding of CAP to virus particles, and b) CAP binding to virus particles in the presence or absence of sCD4 would elicit conformational changes which could affect HIV-1 infectivity.
Pretreatment with CAP impairs gp120 binding to coreceptors
Earlier studies describing the underlying molecular mechanisms involved in the HIV-1 inhibitory effect of the candidate microbicide CAP indicated that this compound remains bound to HIV-1, impairing virus infectivity by blockade of binding sites for cellular coreceptors CXCR4 and CCR5 [ 8 ] . Results reported here further extend these findings and show that: 1) there is synergism between sCD4 and CAP for inhibition of virus infectivity; 2) CAP binding to HIV-1 leads to conformational changes in viral envelope glycoproteins resulting in the expression of functionally inert six-helix bundle structures.
These results indicate that treated HIV-1 particles, utilizing either CXCR4 or CCR5 as coreceptors, retain CAP on their surface and suggest that this is responsible for the altered properties and impaired infectivity of the treated viruses.
Thus, CAP would be expected to affect one or more steps required for HIV-1 entry into cells, i.e. binding to cellular CD4, to the major HIV-1 coreceptors CXCR4 or CCR5 for X4 and R5 viruses [ 6 ] , respectively, and fusion with cell membranes [ 7 8 9 10 11 12 13 14 15 ] . Results presented here show that CAP pretreated HIV-1 has a reduced capacity to bind to the coreceptors leading to impaired virus infectivity.
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