Dengue virus sustains viability of infected cells by counteracting apoptosis-mediated DNA breakage

NS1, a virotoxin, abundantly present in Dengue patients blood, is a major player behind disease patho-biogenesis including plasma leakage. Despite the presence of NS1 in blood, Dengue is asymptomatic and self-limiting in more than;80% dengue virus (DV) infected people. We investigated this observation and found that plasmid-mediated NS1 expression and secretion in cells are sufficient to cause programmed cell death (apoptosis) and associated cellular DNA breakage. However, cells infected with dengue virus and secreting equivalent amounts of NS1 did not exhibit apoptotic DNA breakage. Consequently, DV-infected cells showed better survival than cells in which only NS1 was transiently expressed by transfection with expression plasmid. We also found that DV can even prevent chemical-induced apoptotic DNA damage in infected host cells. So, DV bypasses host antiviral defense i.e. apoptosis by counteracting cellular DNA breakages and keeps the infected cells metabolically active to prolong virus replication.