Myeloid-related protein (MRP)-8 from cervico-vaginal secretions activates HIV replication.
OBJECTIVE
To identify a substance found in female genital tract secretions that enhances HIV expression in infected cells.


METHODS
Cervico-vaginal lavages (CVL), collected in sterile normal saline, were fractionated and tested for HIV-inducing activity using HIV-infected monocytes.


METHODS
To purify the component(s) of CVL that enhance HIV production, Mono-Q ion exchange chromatography followed by Superose-12 molecular sieve analysis, and SDS--PAGE were performed. The purified protein was identified by amino acid sequence analysis.


RESULTS
SDS--PAGE of bioactive fractions showed a 14 kDa polypeptide band. Amino acid sequence analysis of selected peptides from the 14 kDa band showed 100% homology with the myeloid-related protein (MRP)-8, an inflammatory protein found in mucosal secretions. Western blot analysis revealed that bioactive CVL contained more immunoreactive MRP-8 than samples without bioactivity. 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 reduce risk of sexual as well as maternal--infant transmission of HIV.
Hashemi
F B
FB
Department of Immunology/Microbiology, Section of Infectious Diseases, Rush Medical College, Chicago, Illinois 60612, USA.
Mollenhauer
J
J
Madsen
L D
LD
Sha
B E
BE
Nacken
W
W
Moyer
M B
MB
Sorg
C
C
Spear
G T
GT
D000595:Amino Acid Sequence; D000943:Antigens, Differentiation / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D002135:Calcium-Binding Proteins / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D040501:Calgranulin A; D002460:Cell Line; D002584:Cervix Uteri / Q000737:chemistry / Q000378:metabolism*; D005260:Female; D015497:HIV-1 / Q000235:genetics*; D006801:Humans; D011994:Recombinant Proteins / Q000494:pharmacology; D014621:Vagina / Q000737:chemistry / Q000378:metabolism*; D014775:Virus Activation
D000943:Antigens, Differentiation; D002135:Calcium-Binding Proteins; D040501:Calgranulin A; D011994:Recombinant Proteins