Understanding the role of GCN2 mediated amino acid sensing pathway in the pathogenesis of Dengue virus infection

Abstract

DENV infection is expanding at an alarming rate and is currently one of the most frequent resurging viral infections globally. With an estimated ~400 million infections annually (Aguirre et al., 2017; Jayathilaka et al., 2018; N. E. A. Murray, Quam, & Wilder-Smith, 2013), Dengue indeed embodies a global threat. The continuous resurgence and expansion of Dengue is predominantly attributed to the geographical expansion of both vector and virus with many urban areas of tropics witnessing hyperendemic state and non-availability of an effective licensed Dengue vaccine capable of neutralizing all DENV serotypes (Afroz, Giddaluru, Manzar Abbas, & Khan, 2016; Bhatt et al., 2013). Lack of a coherent archetype to discourse the pathological impacts of Dengue as well as the strategies employed by the virus to evade the host immune responses has created enormous challenges for the designing of a safe, efficacious therapeutic interventions against DENV infection (McArthur, Sztein, & Edelman, 2013). The efforts for designing Dengue vaccine dates back to the Second World war when the virus strains were isolated(Rothman, 2011). While the pace towards Dengue vaccine development since then has been considerably unsatisfactory, the incidence and geographical range of Dengue has increased to greater than 30 fold across most of the subtropical and tropical regions worldwide(Maria G Guzman, Gubler, Izquierdo, Martinez, & Halstead, 2016; Rothman, 2011). The unavailability of an appropriate animal model(Afroz et al., 2016) that can reproduce human disease has made it even more challenging to design a potent vaccine against Dengue. The slow progress towards Dengue vaccine development indicates the rare challenges the disease brings with itself.