Dengue Virus Cellular Receptors and Tropism

Abstract

Viral entry into host cells primordially defines tropism and represents an attractive target to counteract infection either by antiviral agents or by immune mediated mechanisms. Research on Dengue virus entry presents interesting challenges. Whatever the mechanism dengue virus exploits to gain entry into cells, this had to be evolutionarily conserved, so that it is now present in arthropod and human cells. Until now, dengue cellular receptors were not completely unraveled. However, we have clues about the key steps dengue virus is relying on. Initially a group of factors that interact with the virus through carbohydrate interaction assure its adherence and further contact with a protein receptor complex, which is held together thanks to its special interaction with cell membrane lipidic platforms. This interaction may be so intimate that it may trigger not only viral entry through receptormediated endocytosis, but also activation of cell signaling pathways that the virus is going to subvert to its advantage.

Insight into the Tropism of Dengue Virus in Humans

“…Hence further studies would exaggerate our insight into the tropism of DENV in regard to these cells and help in identifying its new replication source/s. c. Activated monocytes and U937 cells prM and NS3 [17,125,127,128,[148][149][150] d. Blood-derived DCs Negative-sense (−) and positive-sense (+) RNA, DENV E and NS1 [25,124,126,151,152] resident macrophages (and other unknown cells) are infected and carry the virus to the lymphatic and vascular system, leading to the infection of bone marrow and spleen. (4) and (5) Later, Peyer's patches and lymph nodes are infected and might receive DENV directly from DLNs or via bone marrow and spleen.…”

Gene Expression Profiling of Different Huh7 Variants Reveals Novel Hepatitis C Virus Host Factors

“…In fact, only the Huh7 cell line-and especially some derived clones and subclones-proved to be robustly permissive to HCV in vitro [25]. This extreme degree of host cell selectivity is in contrast to even rather closely related viruses, such as the Flaviviruses [84][85][86], and likely reflects HCV's finely tuned virus-host-interface that also permits the virus to replicate persistently within a cell.…”

The Role of Host Cholesterol During Flavivirus Infection

“…In this step, the viral particles have to bind to specific molecules on the cell surface such as receptors and coreceptors to enter into the host cell (Figure 1A ). Since several of the attachment and receptor molecules described for viruses are present in lipid rafts (Takahashi and Suzuki, 2009 ), lipids and cholesterol-rich plasma membrane microdomains that are essential during entry of DENV (Lee et al, 2008 ; Puerta-Guardo et al, 2010 ; Soto-Acosta et al, 2013 ; García Cordero et al, 2014 ; Reyes-del Valle et al, 2014 ; Diwaker et al, 2015 ), and WNV (Medigeshi et al, 2008 ) (Figure 1A ). The use of cholesterol-depleting drugs such as methyl-β-cyclodextrin (MβCD) or filipin, which binds to cellular cholesterol forming complexes and avoiding the formation of lipid rafts before viral entry.…”

“…This observation suggests the formation of lipoviroparticles (LVPs) in DENV infection. However, the presence of LVPs has not been observed during in vivo DENV infection, and the direct function of LVPs in DENV attachment or entry steps has not been analyzed (Reyes-del Valle et al, 2014 ). Besides, there is a report where apolipoprotein A-1 (Apo A-1), the main component of high-density lipoprotein (HDL), interact with DENV particles and facilitates viral entry through the scavenger receptor class B type I (SR-BI), the cell receptor for Apo A-I (Li et al, 2013 ) (Figure 1A ).…”