Limitations of the human-PBL-SCID mouse model for vaginal transmission of HIV-1.
OBJECTIVE
SCID mice reconstituted with human peripheral blood lymphocytes (PBL) are amenable to vaginal transmission of HIV-1. We investigated the effectiveness of this model to establish systemic HIV-1 infection.


METHODS
Eighty progesterone-primed C.B-17 SCID mice were reconstituted with human-PBLs and intravaginally inoculated with CCR5 HIV-1 (BaL or 92BR09) infected human-PBLs in the presence of human semen. After two weeks, viral RNA load in spleen, peritoneal lavage (PL), and serum was quantitated by the nucleic acid sequence-based amplification method.


RESULTS
In five independent experiments, spleen from 8/60 (13.3%), PL from 7/60 (11.6%), and serum from 16/56 (28.5%) mice were positive for BaL HIV-1 infection. Similarly, spleen from 4/20 (20%), PL from 1/20 (5%) and serum from 5/20 (25%) mice vaginally inoculated with 92BR09-infected human-PBLs were positive for HIV-1. A one-sided power analysis using normal approximation revealed that at 5% significance level, the overall response rate need to increase form 0.29 to 0.9 and 80% of the control groups needs to achieve a response rate between 6/10 and 9/10 to make the assay feasible.


CONCLUSIONS
The incidence of vaginal transmission of CCR5 HIV-1 in the human-PBL-SCID mouse was low and variable, which constitutes a major disadvantage for preclinical evaluation of vaginal microbicides.
D'Cruz
Osmond J
OJ
Parker Hughes Institute, St Paul, MN 55113, USA. odcruz@ih.org
Uckun
Fatih M
FM
D000818:Animals; D001202:Ascitic Fluid / Q000821:virology; D004195:Disease Models, Animal; D005240:Feasibility Studies; D005260:Female; D015658:HIV Infections / Q000635:transmission* / Q000821:virology; D015497:HIV-1 / Q000235:genetics*; D006801:Humans; D017710:Lymphocyte Transfusion; D008214:Lymphocytes / Q000821:virology*; D008297:Male; D051379:Mice; D016513:Mice, SCID; D016133:Polymerase Chain Reaction / Q000379:methods; D012367:RNA, Viral / Q000097:blood*; D013154:Spleen / Q000821:virology; D013997:Time Factors; D014621:Vagina / Q000821:virology*; D019562:Viral Load
D012367:RNA, Viral