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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
agricultural and biological sciences
Anti-HIV-1 activity of elafin is more potent than its precursor's, trappin-2, in genital epithelial cells
Journal of Virology, Volume 86, No. 8, Year 2012
Notification
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Description
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. © 2012, American Society for Microbiology.
Authors & Co-Authors
Drannik, Anna
Canada, Hamilton
Michael G. Degroote Institute for Infectious Disease Research
Nag, Kakon
Canada, Hamilton
Michael G. Degroote Institute for Infectious Disease Research
Yao, Xiaodan
Canada, Hamilton
Michael G. Degroote Institute for Infectious Disease Research
Henrick, Bethany M.
Canada, Hamilton
Michael G. Degroote Institute for Infectious Disease Research
Jain, Sumiti
Canada, Hamilton
Michael G. Degroote Institute for Infectious Disease Research
Blake Ball, T.
Canada, Winnipeg
University of Manitoba
Canada, Ottawa
Public Health Agency of Canada
Plummer, Francis Allan
Canada, Winnipeg
University of Manitoba
Canada, Ottawa
Public Health Agency of Canada
Wachihi, Charles
Kenya, Nairobi
University of Nairobi
Kimani, Joshua
Kenya, Nairobi
University of Nairobi
Rosenthal, Kenneth Lee
Canada, Hamilton
Michael G. Degroote Institute for Infectious Disease Research
Statistics
Citations: 29
Authors: 10
Affiliations: 4
Identifiers
Doi:
10.1128/JVI.06561-11
ISSN:
0022538X
e-ISSN:
10985514
Research Areas
Infectious Diseases
Sexual And Reproductive Health