Title:	HIV-1 Tat protein enhances the intracellular growth of Leishmania amazonensis via the ds-RNA induced protein PKR
Authors:	Vivarini, Aislan de Carvalho Pereira, Renata de Meirelles Santos Souza, Victor Barreto de Temerozo, Jairo Ramos Soares, Deivid C. Saraiva, Elvira M. Saliba, Alessandra Mattos Bou-Habib, Dumith Chequer Lopes, Ulisses Gazos
Affilliation:	Universidade Federal do Rio Janeiro. Centro de Ciências da Saúde. Instituto de Biofísica Carlos Chagas Filho. Laboratório de Parasitologia Molecular. Rio de Janeiro, RJ, Brasil. Universidade Federal do Rio Janeiro. Centro de Ciências da Saúde. Instituto de Biofísica Carlos Chagas Filho. Laboratório de Parasitologia Molecular. Rio de Janeiro, RJ, Brasil. Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Pesquisa sobre o Timo. Rio de Janeiro, RJ, Brasil. Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Pesquisa sobre o Timo. Rio de Janeiro, RJ, Brasil. Universidade Federal do Rio Janeiro. Instituto de Microbiologia Paulo Góes. Laboratório de Imunobiologia de Leishmanioses. Rio de Janeiro, RJ, Brasil. Universidade Federal do Rio Janeiro. Instituto de Microbiologia Paulo Góes. Laboratório de Imunobiologia de Leishmanioses. Rio de Janeiro, RJ, Brasil. Universidade do Estado do Rio de Janeiro. Faculdade de Ciências Médicas. Departamento de Microbiologia. Rio de Janeiro, RJ, Brasil. Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Pesquisa sobre o Timo. Rio de Janeiro, RJ, Brasil. Universidade Federal do Rio Janeiro. Centro de Ciências da Saúde. Instituto de Biofísica Carlos Chagas Filho. Laboratório de Parasitologia Molecular. Rio de Janeiro, RJ, Brasil.
Abstract:	HIV-1 co-infection with human parasitic diseases is a growing public health problem worldwide. Leishmania parasites infect and replicate inside macrophages, thereby subverting host signaling pathways, including the response mediated by PKR. The HIV-1 Tat protein interacts with PKR and plays a pivotal role in HIV-1 replication. This study shows that Tat increases both the expression and activation of PKR in Leishmania-infected macrophages. Importantly, the positive effect of Tat addition on parasite growth was dependent on PKR signaling, as demonstrated in PKR-deficient macrophages or macrophages treated with the PKR inhibitor. The effect of HIV-1 Tat on parasite growth was prevented when the supernatant of HIV-1-infected macrophages was treated with neutralizing anti-HIV-1 Tat prior to Leishmania infection. The addition of HIV-1 Tat to Leishmania-infected macrophages led to inhibition of iNOS expression, modulation of NF-kB activation and enhancement of IL-10 expression. Accordingly, the expression of a Tat construct containing mutations in the basic region (49-57aa), which is responsible for the interaction with PKR, favored neither parasite growth nor IL-10 expression in infected macrophages. In summary, we show that Tat enhances Leishmania growth through PKR signaling.
Keywords:	HIV-1 Tat protein Leishmania amazonensis protein PKR ds-RNA
DeCS:	HIV-1 Produtos do Gene tat Leishmania braziliensis eIF-2 Quinase
Issue Date:	2015
Publisher:	Nature Publishing Group
Citation:	VIVARINI, Aislan de Carvalho; et al. HIV-1 Tat protein enhances the intracellular growth of Leishmania amazonensis via the ds-RNA induced protein PKR. Scientific Reports, v.5:16777, 11p, Nov. 2015.
DOI:	10.1038/srep16777
ISSN:	2045-2322
Copyright:	open access
Appears in Collections:	IOC - Artigos de Periódicos

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