Dengue virus clinical isolates sustain viability of infected hepatic cells by counteracting apoptosis-mediated DNA breakage

Abstract

NS1, a virotoxin, abundantly present in Dengue patients blood, is a major player behind disease patho-biogenesis including plasma leakage and damage to the liver. Despite the presence of NS1 in blood, Dengue is asymptomatic and self-limiting in [≥]80% Dengue virus (DV) infected people. We investigated this observation and found that plasmid-mediated NS1 expression and secretion in liver cells (Huh7) are sufficient to cause programmed cell death (apoptosis) and associated cellular DNA breakage. However, liver or kidney cell lines infected with DV and secreting equivalent amounts of NS1 didnt exhibit apoptotic DNA breakage. In fact, DV-infected cells showed better survival than cells in which only NS1 was transiently expressed by transfection. We also found that DV can even prevent chemical-induced apoptotic DNA damage in infected host cells. So, DV thwarts host antiviral defence i.e. apoptosis, by counteracting cellular DNA breakages and keeps the infected cells metabolically active to prolong virus replication.