Objectives: To identify a substance found in female genital tract secretion
s that enhances HIV expression in infected cells.
Design: Cervico-vaginal lavages (CVL), collected in sterile normal saline,
were fractionated and tested for HIV-inducing activity using HIV-infected m
onocytes.
Methods: To purify the component(s) of CVL that enhance HIV production, Mon
o-Q ion exchange chromatography followed by Superose-12 molecular sieve ana
lysis, and SDS-PAGE were performed. The purified protein was identified by
amino acid sequence analysis.
Results: SDS-PACE of bioactive fractions showed a 14 kDa polypeptide band.
Amino acid sequence analysis of selected peptides from the 14 kDa band show
ed 100% homology with the myeloid-related protein (MRP)-8, an inflammatory
protein found in mucosal secretions. Western blot analysis revealed that bi
oactive CVL contained more immunoreactive MRP-8 than samples without bioact
ivity. The HIV-inducing activity of MRP-8 was further confirmed by showing
that human recombinant MRP-8 increased HIV expression by up to 40-fold.
Conclusions: MRP-8 in cervico-vaginal secretions stimulates HIV production.
Strategies aimed at blocking MRP-8 activity in the genital tract could red
uce risk of sexual as well as maternal-infant transmission of HIV. (C) 2001
Lippincott Williams & Wilkins.