Dendritic Cell Precursors Are Permissive to Dengue Virus and Human Immunodeficiency Virus Infection

Abstract

CD14؉ interstitial cells reside beneath the epidermis of skin and mucosal tissue and may therefore play an important role in viral infections and the shaping of an antiviral immune response. However, in contrast to dendritic cells (DC) or blood monocytes, these antigen-presenting cells (APC) have not been well studied. We have previously described long-lived CD14؉ cells generated from CD34 ؉ hematopoietic progenitors, which may represent model cells for interstitial CD14؉ APC. Here, we show that these cells carry DC-SIGN and differentiate into immature DC in the presence of granulocyte-macrophage colony-stimulating factor. We have compared the CD14 ؉ cells and the DC derived from these cells with respect to dengue virus and human immunodeficiency virus type 1 (HIV-1) infection. Both cell types are permissive to dengue virus infection, but the CD14؉ cells secrete the anti-inflammatory cytokine interleukin 10 and no tumor necrosis factor alpha. Regarding HIV, the CD14 ؉ cells are permissive to HIV-1, release higher p24 levels than the derived DC, and more efficiently activate HIV Pol-specific CD8؉ memory T cells. The CD14 ؉ DC precursors infected with either virus retain their DC differentiation potential. The results suggest that interstitial CD14 ؉ APC may contribute to HIV-1 and dengue virus infection and the shaping of an antiviral immune response.

Dengue Virus Utilizes a Novel Strategy for Translation Initiation When Cap-Dependent Translation Is Inhibited

“…The biological relevance of the reduced dependence of DEN translation on eIF4E may correlate with the ability of DEN to translate under conditions in which cellular translation is limited, for example, in differentiated cells such as myeloid and dendritic cells, known to be in vivo targets of DEN, that contain lower levels of available eIF4E (29,41). Consistent with this hypothesis, we have previously shown that an increase in DEN replication coincides with differentiation in human myeloid cells (42), and we are currently evaluating whether translation of DEN proteins and functionally and nonfunctionally capped DEN RNA constructs also increases under these conditions. In addition, mammalian cellular stress response and immune functions, such as the interferon antiviral response (24), may compel viral translation by one mechanism over the other.…”

Dengue

“…When the virus is introduced into the skin, the first target cell is the dendritic cell present in the epidermis (Palucka, 2000;Kwan et al, 2005), especially the Langerhans cells, which are activated and present the virus to the lymphocyte t. similarly, the viruses that have broken into the blood are identified by the monocyte and endothelial cells, which also perform the presenting function. the first lymphocytes to be activated are the Cd4 and then the Cd8, with the release of cytokines (Cardier et al, 2005).…”

Targeted Delivery of Small Interfering RNA to Human Dendritic Cells To Suppress Dengue Virus Infection and Associated Proinflammatory Cytokine Production

“…Following the bite of an infected Aedes mosquito, the initial local viral replication is believed to take place in the skin DCs, including myeloid DCs and Langerhans cells (31,53,59). Dengue-infected DCs play a key role in the immunopathogenesis of DHF/DSS, as, along with macrophages, they release proinflammatory cytokines and soluble factors that mediate plasma leakage, thrombocytopenia, and hypovolemic shock associated with severe dengue infection (14,15,29,38).…”