Influenza A viruses (IAV) are contagious pathogens responsible of seasonal respiratory tract infections in both humans and animals worldwide. Upon infection, the innate immune system provides the first line of defense to limit viral replication. This fast and broadly response brings the cells into an alerted state, ultimately leading to the induction and production of interferon (IFN). At the same time, IAV have developed very diverse mechanisms and strategies of immune evasion in order to avoid or circumvent the host antiviral response and promote viral replication. Many of these functions are mediated by the viral protein NS1 which is considered as a multitasking virulence factor and the main antagonist of the innate immune response during IAV infection. My research at the García-Sastre laboratory is mainly focused in characterizing the mechanisms by which NS1 is able to adapt to different hosts as well as identifying novel NS1-host interactors. Making use of classical molecular biology techniques in combination with cutting edge high throughput deep sequencing and OMICs approaches will help us to identify new targets and design novel therapies and more effective vaccines and antivirals against IAV.
Jahan AS, Biguand E, Muñoz-Moreno R, Le Quang A, Mok CK, Wong HH, Teo QW, Valkenburg SA, Chin AWH, Man Poon LL, Te Velthuis A, García-Sastre A, Demeret C, Sanyal S. OTUB1 Is a Key Regulator of RIG-I-Dependent Immune Signaling and Is Targeted for Proteasomal Degradation by Influenza A NS1. Cell Rep. 2020 Feb 4;30(5):1570-1584.
Muñoz-Moreno R, Martínez-Romero C, Blanco-Melo D, Forst CV, Nachbagauer R, Benitez AA, Mena I, Aslam S, Balasubramaniam V, Lee I, Panis M, Ayllón J, Sachs D, Park MS, Krammer F, tenOever BR, García-Sastre A. Viral Fitness Landscapes in Diverse Host Species Reveal Multiple Evolutionary Lines for the NS1 Gene of Influenza A Viruses. Cell Rep. 2019 Dec 17;29(12):3997-4009.
Monteagudo PL, Muñoz-Moreno R, Fribourg M, Potla U, Mena I, Marjanovic N, Hartmann BM, Sealfon SC, García-Sastre A, Ramos I, Fernández-Sesma A. Differential Modulation of Innate Immune Responses in Human Primary Cells by Influenza A Viruses Carrying Human or Avian Nonstructural Protein 1. J Virol. 2019 Dec 12;94(1). pii: e00999-19.
Zhang K, Xie Y, Muñoz-Moreno R, Wang J, Zhang L, Esparza M, García-Sastre A, Fontoura BMA, Ren Y. Structural basis for influenza virus NS1 protein block of mRNA nuclear export. Nat Microbiol. 2019 Oct;4(10):1671-1679.
Thompson MG, Muñoz-Moreno R, Bhat P, Roytenberg R, Lindberg J, Gazzara MR, Mallory MJ, Zhang K, García-Sastre A, Fontoura BMA, Lynch KW. Co-regulatory activity of hnRNP K and NS1-BP in influenza and human mRNA splicing. Nat Commun. 2018 Jun 19;9(1):2407.