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Abstract



ACTIVATION OF HUMAN IMMUNODEFICIENCY VIRUS BY LEISHMANIA DONOVANI IN HUMAN TONSILLAR TISSUE CULTURED EX VIVO

C. Zhao, M.J. Tremblay
Centre de Recherche en Infectiologie, Pavillon CHUL et Département de Biologie médicale, Faculté de médecine, Université Laval, Ste-Foy, Québec, Canada


Parasitic infections, such as leishmaniasis, can modulate the life cycle of human immunodeficiency virus (HIV) and disease progression. In fact, HIV/Leishmania co-infection has been emerging as an extremely serious, new disease and threat in many countries. Although there are numerous clinical evidences supporting the co-factor role played by Leishmania in HIV-infected patients, there is a paucity of data with respect to the molecular events underlying the effects of HIV/Leishmania co-infection in the process of HIV infection. In the present study we wanted to explore the putative modulatory effect(s) on the process of HIV replication using human lymphoid tissue, which is considered as a major in vivo site of virus production. We found that the protozoan parasite Leishmania enhances both HIV-1 transcription and virus production following infection of human tonsillar tissues cultured ex vivo with strains of HIV-1 bearing distinct co-receptor usage profiles (i.e. T-tropic, macrophage-tropic, and dual-tropic). Furthermore, we demonstrated that the Leishmania-mediated increase in HIV production was severely diminished by a treatment with pentoxifylline, a known down-regulator of the production of proinflammatory cytokines, particularly TNF-?. These results suggest that Leishmania increases HIV production in human lymphoid tissue cultured ex vivo through cytokine dysregulation mechanisms and that TNF-α secretion was pivotal in this process. Our findings raise the idea that pentoxifylline might be considered as a potential adjuvant for the treatment of individuals co-infected with both HIV and Leishmania. This work also indicates that histocultures of human lymphoid tisue infected ex vivo with both pathogens represents an ideal experimental cell system to scrutinize putative bi-directional interactions between HIV and Leishmania in a human microenvironment.





The 2nd IAS Conference on HIV Pathogenesis and Treatment
Abstract no. 902


Suggested Citation
" C. Zhao, et al. ACTIVATION OF HUMAN IMMUNODEFICIENCY VIRUS BY LEISHMANIA DONOVANI IN HUMAN TONSILLAR TISSUE CULTURED EX VIVO. Poster: The 2nd IAS Conference on HIV Pathogenesis and Treatment: Abstract no. 902"