Kaposi's-sarcoma-associated-herpesvirus-activated dendritic cells promote HIV-1 trans-infection and suppress CD4+ T cell proliferation

Abstract

Infection of Kaposi's sarcoma-associated herpesvirus (KSHV) is commonly occurred in AIDS patients. KSHV and HIV-1 act cooperatively in regulating infection with each other and in human carcinogenesis. Dendritic cells (DCs), as the pivotal cells in host immunity, may be modulated by both viruses, for immunoevasion and dissemination, therefore, the interaction between DCs and each virus has been a prior focus for pathogenesis elucidation. Here, we assessed the potential effect of KSHV on DC-HIV-1 interaction. We found that KSHV stimulation could promote maturation of monocyte-derived DCs (MDDCs) and impaired the ability of MDDCs to drive proliferation of resting CD4(+) T cells, demonstrating the immunosuppression induced by KSHV. More importantly, KSHV-stimulated MDDCs could capture more HIV-1 and efficiently transferred these infectious viruses to Hut/CCR5 T cell line. Our results reveal the novel modulation of DC-mediated HIV-1 dissemination by KSHV, and highlight the importance of studying DC-HIV-1 interaction to elucidate HIV/AIDS pathogenesis.

Células dendríticas plasmocitóides, expressão de receptores "Toll-like" 9 e 3 e de podoplanina nas lesões cutâneas do Sarcoma de Kaposi associado à síndrome de imunodeficiência adquirida e esporádico

“…Células dendríticas infectadas pelo HHV-8 são estimuladas, passando a capturar mais partículas do HIV e transmitindo-o para os linfócitos T CD4+ (Liu et al, 2013). LANA ativa a transcrição do HIV pois interage, de maneira sinérgica, com Tat.…”

“…Existem mecanismos de cooperação mútua desses dois vírus tanto na patogênese como na carcinogênese do SK de Oliveira, 2011). A imunodepressão causada pelo HIV facilita a evasão do HHV-8 dos mecanismos da imunidade, assim como o processo de carcinogênese (Liu et al, 2013). Além disso, o HIV induz a reativação e replicação lítica do HHV-8 (Harrington et al, 1997).…”