Evasion of Influenza A Viruses from Innate and Adaptive Immune Responses.docVIP

Viruses 2012, 4, 1438-1476; doi:10.3390/v4091438 OPEN ACCESS viruses ISSN 1999-4915 /journal/viruses Review Evasion of Influenza A Viruses from Innate and Adaptive Immune Responses Carolien E. van de Sandt, Joost H. C. M. Kreijtz and Guus F. Rimmelzwaan * Department of Virology, ErasmusMC, Dr. Molewaterplein 50, 3015 GE, Rotterdam, The Netherlands; E-Mails: c.vandesandt@erasmusmc.nl (C.E.S.); j.kreijtz@erasmusmc.nl (J.H.C.M.K.) * Author to whom correspondence should be addressed; E-Mail: g.rimmelzwaan@erasmusmc.nl; Tel.: +31-10-704-4243; Fax: +31-10-704-4760. Received: 3 July 2012; in revised form: 10 August 2012 / Accepted: 22 August 2012 / Published: 3 September 2012 Abstract: The influenza A virus is one of the leading causes of respiratory tract infections in humans. Upon infection with an influenza A virus, both innate and adaptive immune responses are induced. Here we discuss various strategies used by influenza A viruses to evade innate immune responses and recognition by components of the humoral and cellular immune response, which consequently may result in reduced clearing of the virus and virus-infected cells. Finally, we discuss how the current knowledge about immune evasion can be used to improve influenza A vaccination strategies. Keywords: influenza; evasion; innate immunity; adaptive immunity 1. Introduction Influenza viruses belong to the family of orthomyxoviridae and are one of the leading causes of respiratory tract infections in humans [1]. Yearly, influenza viruses cause an estimated 3–5 million severe clinical infections and 250,000–500,000 fatal cases [2,3]. The genome of influenza A viruses consists of eight gene segments of single-stranded negative-sense RNA encoding 12 proteins: surface glycoproteins, hemaglutinin (HA) and neuraminidase (NA), two matrix proteins (M1 and M2), the nucleoprotein (NP), three polymerase complex proteins PB1, PB2 and PA, and four non-structural