**5. Virus-host interactions**

different viral strains and serotypes. Although most of the DENV proteins are with known

DENV is mostly introduced in human by infected *Ae. aegypti* mosquitoes. After the introduction, DENV particularly targets mononuclear phagocyte lineage cells including the skin resistant Langerhans cells [31, 32]. However, in mosquitoes, DENV is thought to initially target midgut and then extends and replicate in other peripheral tissues [33]. DENV can infect a very diverse range of cell lines including human, mosquito, monkey, hamster, and murine cell linages. This suggests that either DENV uses a ubiquitous receptor or it uses multiple receptors for its entry [33]. In mosquito cells, different independent groups have reported many potential DENV receptors like heat shock protein 70 (HSP), R80, R60, and 45 kDa protein [33]. In human beings, heparan sulfate [34], Hsp90 [35], CD14 [36], GRP78/BiP [37], and a 37/67-kDa high-affinity laminin receptor have been reported [38]. DENV particles interact with human myeloid cells by C-type lectin receptors (CLR) including DC-specific intracellular adhesion molecule 3 (ICAM-3)-grabbing no integrin (DC-SIGN, CD209) [39, 40], mannose

receptor (MR), and C-type lectin domain family 5, member A (CLEC5, MDL-1) [41].

functions but some remains to be explored (**Table 1**) [31].

**Table 1.** Functions of DENV genome structural and nonstructural proteins.

96 Current Topics in Tropical Emerging Diseases and Travel Medicine

**3. Viral entry**

In nature, almost every organism engages in ecological or molecular interactions whether antagonistic or mutualistic with other organisms of different species to thrive and excel. These interactions are major drivers of diversification and adaptive evolution. Among these interactions, most fascinating examples are those involved in invertebrate susceptibility to pathogens [50]. According to a recent study, the susceptibility of *Ae. aegypti* to dengue virus has a genetic basis for genotype-by-genotype interactions [51]. It is evident by the fact that despite pathogenic nature of dengue virus in human, its interaction with *Ae. aegypti* mosquito is somehow mutualistic. DENV has somehow improvised to overcome mosquito defenses and manipulate its cellular machinery in a way still not well known that emancipates its replication without interfering too much with normal growth of mosquitos.
