HIV-1 infectivity and host range modification by cathepsin D present in human vaginal secretions.
OBJECTIVE
To investigate HIV-1 infectivity in the natural environment of vaginal secretions.


METHODS
Vaginal wash samples collected from 14 healthy women were incubated in vitro with various HIV-1 strains for 10 min at 37 degrees C and then assayed for infectivity on primary lymphocyte cultures, or on CEM cells, or on CD4- ME180 cells derived from vaginal epithelium.


METHODS
HIV-1 infectivity was measured by early virus growth in the various host cells tested using a quantitative p24 assay and by the Karber procedure.


RESULTS
Preincubation of HIV-1(IIIB) with vaginal wash samples or 2 microg/ml cathepsin D increased the ability of the virus to grow in lymphocyte cultures. The vaginal wash effect was abolished by 5 microg/ml pepstatin A, an inhibitor of aspartyl proteases. Presence of precursor and mature forms of cathepsin D in vaginal wash was demonstrated after passage through a pepstatin A-agarose column. Median tissue culture infective doses of HIV-1(IIIB) and HIV-1(JRFL) strains were increased 14.4-fold and 18-fold, respectively, after preincubation in vaginal wash sample, and were increased by pretreatment with 2 microg/ml cathepsin D. When CD4 receptors of CEMss cells were blocked by OKT4a monoclonal antibody, the cells lost susceptibility to HIV-1 (IIIB), but supported the growth of virus pretreated with vaginal wash sample or cathepsin D. These treated viruses were able to initiate infection of CD4-ME180 epithelial cells, which were not receptive to untreated virus. ME180 cells were shown to possess the messenger of CXC-chemokine receptor-4.


CONCLUSIONS
Vaginal secretions may help HIV-1 transmission to women by increasing infectivity for CD4+ cells and allowing entrance into some CD4-epithelial cells.
El Messaoudi
K
K
Department of Applied Genetics, Faculty of Sciences, Erasme Hospital, Université Libre de Bruxelles, Nivelles, Belgium.
Thiry
L
L
Van Tieghem
N
N
Liesnard
C
C
Englert
Y
Y
Moguilevsky
N
N
Bollen
A
A
D015496:CD4-Positive T-Lymphocytes / Q000821:virology; D002402:Cathepsin D / Q000302:isolation & purification / Q000378:metabolism* / Q000494:pharmacology; D002478:Cells, Cultured; D005260:Female; D016655:HIV Core Protein p24 / Q000378:metabolism; D015658:HIV Infections / Q000635:transmission / Q000821:virology*; D015497:HIV-1 / Q000254:growth & development* / Q000472:pathogenicity*; D006801:Humans; D019713:Receptors, CCR5 / Q000378:metabolism; D019718:Receptors, CXCR4 / Q000378:metabolism; D014621:Vagina / Q000276:immunology / Q000378:metabolism* / Q000821:virology
D016655:HIV Core Protein p24; D019713:Receptors, CCR5; D019718:Receptors, CXCR4; D002402:Cathepsin D