Macaca fascicularis are highly susceptible to an RT-SHIV following intravaginal inoculation: a new model for microbicide evaluation.
BACKGROUND
Human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) is a major target for antiretroviral strategy to block or curtail HIV infection. A suitable RT-SHIV/macaque model is urgently needed for the evaluation of HIV/AIDS therapies and microbicides specifically targeting HIV-1 RT.


METHODS
Fifteen cynomolgus macaques (Macaca fascicularis) were divided into three groups (n = 5) and intravaginally inoculated with 4800, 1200, or 300 TCID(50) of RT-SHIVtc. Systemic infections of RT-SHIVtc exposed macaques were determined by both virological and immunologic parameters during 24 weeks post-challenge.


RESULTS
Within 2 weeks post-inoculation, 13 of 15 macaques became infected as confirmed by virus isolation, plasma viral RNA, proviral DNA, declined CD4(+)T cell counts in peripheral blood and seroconversion.


CONCLUSIONS
Results serve to validate the infectivity and pathogenicity of RT-SHIVtc following vaginal exposure in M. fascicularis. This RT-SHIVtc/macaque model could be suitable for the pre-clinical evaluation of non-nucleoside RT inhibitor-based anti-HIV microbicides.
Washington National Primate Research Center, University of Washington, Seattle, WA 98195-7330, USA.
Y
Y
Jiang
B
B
Tian
M B
MB
Agy
M
M
Saifuddin
C-C
CC
Tsai
D000282:Administration, Intravaginal; D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D018791:CD4 Lymphocyte Count; D002460:Cell Line; D004195:Disease Models, Animal; D004198:Disease Susceptibility; D004341:Drug Evaluation; D005260:Female; D015658:HIV Infections; D054303:HIV Reverse Transcriptase; D015497:HIV-1 / Q000276:immunology; D006801:Humans; D008252:Macaca fascicularis; D012367:RNA, Viral / Q000097:blood; D015302:Simian Immunodeficiency Virus / Q000276:immunology
D000914:Antibodies, Viral; D012367:RNA, Viral; D054303:HIV Reverse Transcriptase