dc.contributor.author | Drannik, Anna G | |
dc.contributor.author | Nag, Kakon | |
dc.contributor.author | Yao, Xiao-Dan | |
dc.contributor.author | Henrick, Bethany M | |
dc.contributor.author | Jain, Sumiti | |
dc.contributor.author | Ball, Blake T | |
dc.contributor.author | Plummer, Francis A | |
dc.contributor.author | Wachihi, Charles | |
dc.contributor.author | Kimani, Joshua | |
dc.contributor.author | Rosenthal, Kenneth L | |
dc.date.accessioned | 2013-05-03T12:10:16Z | |
dc.date.available | 2013-05-03T12:10:16Z | |
dc.date.issued | 2012 | |
dc.identifier.citation | J Virol. 2012 April; 86(8): 4599–4610. | en |
dc.identifier.uri | http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3318644/ | |
dc.identifier.uri | http://erepository.uonbi.ac.ke:8080/xmlui/handle/123456789/18701 | |
dc.description | Full text | en |
dc.description.abstract | Cervicovaginal lavage fluid (CVL) is a natural source of anti-HIV-1 factors; however, molecular characterization of the anti-HIV-1 activity of CVL remains elusive. In this study, we confirmed that CVLs from HIV-1-resistant (HIV-R) compared to HIV-1-susceptible (HIV-S) commercial sex workers (CSWs) contain significantly larger amounts of serine antiprotease trappin-2 (Tr) and its processed form, elafin (E). We assessed anti-HIV-1 activity of CVLs of CSWs and recombinant E and Tr on genital epithelial cells (ECs) that possess (TZM-bl) or lack (HEC-1A) canonical HIV-1 receptors. Our results showed that immunodepletion of 30% of Tr/E from CVL accounted for up to 60% of total anti-HIV-1 activity of CVL. Knockdown of endogenous Tr/E in HEC-1A cells resulted in significantly increased shedding of infectious R5 and X4 HIV-1. Pretreatment of R5, but not X4 HIV-1, with either Tr or E led to inhibition of HIV-1 infection of TZM-bl cells. Interestingly, when either HIV-1 or cells lacking canonical HIV-1 receptors were pretreated with Tr or E, HIV-1 attachment and transcytosis were significantly reduced, and decreased attachment was not associated with altered expression of syndecan-1 or CXCR4. Determination of 50% inhibitory concentrations (IC50) of Tr and E anti-HIV-1 activity indicated that E is ~130 times more potent than its precursor, Tr, despite their equipotent antiprotease activities. This study provides the first experimental evidence that (i) Tr and E are among the principal anti-HIV-1 molecules of CVL; (ii) Tr and E affect cell attachment and transcytosis of HIV-1; (iii) E is more efficient than Tr regarding anti-HIV-1 activity; and (iv) the anti-HIV-1 effect of Tr and E is contextual | en |
dc.language.iso | en | en |
dc.subject | HIV-1 | en |
dc.subject | Genital Epithelial Cells | en |
dc.subject | Cervicovaginal lavage fluid | en |
dc.title | Anti-HIV-1 Activity of Elafin Is More Potent than Its Precursor's, Trappin-2, in Genital Epithelial Cells | en |
dc.type | Article | en |
local.publisher | Department of Medical Microbiology | en |