Immune evasion strategies of flaviviruses

Flavivirus is a genus of the family Flaviviridae. It includes West Nile virus (WNV), dengue virus (DENV), yellow fever virus (YFV), Japanese encephalitis virus (JEV), tick-borne encephalitis virus (TBEV), and several other viruses which lead to extensive morbidity and mortality in humans. To establish infection and replication in the hosts, flaviviruses have evolved a variety of strategies to modulate the host's immune responses. In this review, the strategies employed by flaviviruses to evade the innate and adaptive immunity of host are summarized based on current studies, with a major focus on the inhibition of interferon, complement, natural killer (NK) cell, B cell, and T cell responses. This review aims to provide an overview of the current understanding for the mechanisms used by flaviviruses to escape the host's immune response, which will facilitate the future studies on flavivirus pathogenesis and the development of anti-flavivirus therapeutics.

► Flaviviruses have evolved a variety of strategies to modulate the immune responses of host.
► Mechanisms by which flaviviruses evade the innate and adaptive immunity of the host are summarized based on current studies.
► Flaviviruses limit type I IFN signaling by blocking the host gene expression, thus attenuating innate immunity.
► Flaviviruses also inhibit the antiviral immune response of complement system and NK cells.
► High genetic variability of viral antigens allows viral escape from both humoral and cellular immunity against flaviviruses.