HIV coreceptor and chemokine ligand gene expression in the male urethra and female cervix.
OBJECTIVE
Isolates with a tropism for the coreceptor CCR5 are the predominant viral strain transmitted following heterosexual transmission. We have investigated coreceptor expression levels within male and female genital epithelia to assess whether selective transmission can be explained by elevated CCR5 expression within the genital epithelia per se.


METHODS
Individuals attending a local genitourinary medicine unit were recruited, and samples of genital epithelia obtained using either a cytobrush (females) or urethral swab (males). Expression of coreceptor and cell marker mRNAs was then determined by reverse transcription (RT)-PCR.


METHODS
RNA was recovered from the epithelial cell samples then used as templates in competitive quantitative RT-PCR to measure mRNA expression of key chemokines, coreceptors and cell-type markers in the epithelial cell samples. Cell-surface coreceptor expression was also assessed in a sample of patients using fluorescent cell staining.


RESULTS
CXCR4 and CCR3 coreceptors were expressed at significantly higher levels than CCR5 within the female endo- and ectocervix and distal end of the male urethra. Increased levels of cell surface expressed CXCR4 compared to CCR5 was confirmed in samples obtained from the female genital tract by FACS analysis.


CONCLUSIONS
The selective transmission of CCR5-tropic viral variants is unlikely to result simply from differential coreceptor abundance at the genital epithelia.
McClure
C Patrick
CP
Division of Microbiology and Infectious Diseases Institute of Infection, Immunity and Inflammation, University of Nottingham, UK.
Tighe
Patrick J
PJ
Robins
R Adrian
RA
Bansal
Deepa
D
Bowman
Christine A
CA
Kingston
Margaret
M
Ball
Jonathan K
JK
D048868:Adaptor Proteins, Signal Transducing; D000293:Adolescent; D000328:Adult; D000368:Aged; D002352:Carrier Proteins / Q000378:metabolism; D002584:Cervix Uteri / Q000378:metabolism*; D018946:Chemokine CCL5 / Q000378:metabolism; D004847:Epithelial Cells / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000378:metabolism; D054397:Receptors, CCR3; D019713:Receptors, CCR5 / Q000378:metabolism*; D019718:Receptors, CXCR4 / Q000378:metabolism*; D019707:Receptors, Chemokine / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014521:Urethra / Q000378:metabolism*
D048868:Adaptor Proteins, Signal Transducing; C515350:CCR3 protein, human; D002352:Carrier Proteins; D018946:Chemokine CCL5; C493277:MAPKAP1 protein, human; D012333:RNA, Messenger; D054397:Receptors, CCR3; D019713:Receptors, CCR5; D019718:Receptors, CXCR4; D019707:Receptors, Chemokine