Ana Fernandez-Sesma, PhD
Research Topics:AIDS/HIV, Antivirals, Dendritic Cells, Immune Antagonism, Infectious Disease, Inflammation, Influenza Virus, Interferon, Interferon Antagonists, Macrophage, Mucosal Immunology, Viruses and Virology
Watch a video featuring the Microbiology and Virology PhD Graduate School Program.
For a complete list of Dr. Fernandez-Sesma's publications follow this link:
Multi-Disciplinary Training AreasImmunology [IMM], Microbiology [MIC]
MS, University of Salamanca
PhD, Mount Sinai Graduate School (CUNY)
Best Faculty Mentor to Postdoctoral Fellows
Innate immunity to influenza virus and HIV
- Influenza virus is another important human pathogen that causes epidemics yearly in humans as well as occasional pandemics. Influenza virus has been shown by us and others to inhibit important elements of immunity such as the type I interferon (IFN) system as well as the ability of DCs to get activated. As part of our NIH funded Center for research in influenza pathogenesis (CRIP) http://www.mssm.edu/research/centers/center-for-research-on-influenza-pathogenesis/, lead by Dr. Adolfo Garcia-Sastre, in the department of Microbiology at MSSM, http://www.mssm.edu/profiles/adolfo-garcia-sastre#bot, which is one of the Centers of excellence for influenza research (CEIRS) we are using recombinant influenza viruses with specific mutations in several virulence genes, such as the NS1 and HA, among others, and analyzing the ability of different influenza viruses to interfere with different aspects of immunity in primary human systems.
- Human Immunodeficiency virus (HIV), is responsible for one of the most devastating current human epidemics. Our newest project is the study of global innate immune responses to HIV-1 infection in primary human cells. We were recently awarded with an NIH program project grant (HIV immune networks team, or HINT) www.hint.org, with Dr. John Young at the Salk Institute as the principal investigator. This is a multi-investigator program project to study the interactions between HIV and innate immunity. It combines systems biology, molecular virology, innate immunity and viral immunology components. Our project, in collaboration with Dr. Viviana Simon, in the department of Microbiology at MSSM, http://www.mssm.edu/profiles/viviana-a-simon#bot, focuses on the interactions between HIV and primary immune cells (DCs, macrophages and T cells) that may account for the generation of weak adaptive immunity to HIV in patients.
Evasion of innate immunity by dengue virus (DENV)
Specific Clinical/Research Interests Mechanisms of evasion of immunity by dengue and influenza viruses; human immunology in viral infections. Generation of recombinant viruses.
Current Students: Rebecca Hamlin (MDPhD student), Anthony Fredericks (Master Student)
Postdoctoral Fellows: Sebastian Aguirre,PhD, Ana Maestre, PhD, Kevin Maringer, PhD, Irene Ramos, PhD.
Research Personnel: Dabeiba Bernal-Rubio.
Past Members: Sarah Pagni, PhD, Juan R. Rodriguez, PhD, Timothy Savage, MS, Phoenix Bell, MS.
Summary of Research Studies:
The main focuses of study in the Fernandez-Sesma laboratory are the interactions of important human pathogens with primary human immune cells.
- Dengue virus (DENV)is an important human pathogen for which there is no vaccine or treatment available. Dengue is a flavivirus transmitted to humans by the bite of the mosquito aedes aegipti. We are studying the role of different primary human cells, such as dendritic cells (DCs) and macrophages in the initiation or evasion of immunity by DENV. We have analyzed the pattern of gene expression and cytokine secretion in different primary cells after DENV infection and have recently shown that the DENV protease complex (NS2B/3) is crucial for the inhibition of type I IFN production by DENV in primary human DCs, an important step in the generation of the innate and adaptive immune responses by this virus. We are currently studying how primary isolates of DENV are able to initiate or evade immune responses in human primary cells.
- We are also studying adaptation of DENV to human and mosquito cells as part of a DARPA funded multi-investigator project led by Dr. Raul Andino at UCSF. Our laboratory is interested in innate immune evasion by this virus as a measure of adaptation and fitness.
Maringer K, Fernandez-Sesma A. Message in a bottle: lessons learned from antagonism of STING signalling during RNA virus infection. Cytokine & growth factor reviews 2014 Aug;.
Rajsbaum R, Versteeg GA, Schmid S, Maestre AM, Belicha-Villanueva A, Martínez-Romero C, Patel JR, Morrison J, Pisanelli G, Miorin L, Laurent-Rolle M, Moulton HM, Stein DA, Fernandez-Sesma A, tenOever BR, García-Sastre A. Unanchored K48-linked polyubiquitin synthesized by the E3-ubiquitin ligase TRIM6 stimulates the interferon-IKKε kinase-mediated antiviral response. Immunity 2014 Jun; 40(6).
Manganaro L, Pache L, Herrmann T, Marlett J, Hwang Y, Murry J, Miorin L, Ting AT, König R, García-Sastre A, Bushman FD, Chanda SK, Young JA, Fernandez-Sesma A, Simon V. Tumor suppressor cylindromatosis (CYLD) controls HIV transcription in an NF-κB-dependent manner. Journal of virology 2014 Jul; 88(13).
Suthar MS, Aguirre S, Fernandez-Sesma A. Innate immune sensing of flaviviruses. PLoS pathogens 2013 Sep; 9(9).
Ramos I, Krammer F, Hai R, Aguilera D, Bernal-Rubio D, Steel J, García-Sastre A, Fernandez-Sesma A. H7N9 influenza viruses interact preferentially with α2,3-linked sialic acids and bind weakly to α2,6-linked sialic acids. The Journal of general virology 2013 Nov; 94(Pt 11).
Ramos I, Carnero E, Bernal-Rubio D, Seibert CW, Westera L, García-Sastre A, Fernandez-Sesma A. Contribution of double-stranded RNA and CPSF30 binding domains of influenza virus NS1 to the inhibition of type I interferon production and activation of human dendritic cells. Journal of virology 2013 Mar; 87(5).
Stefanidou M, Ramos I, Mas Casullo V, Trépanier JB, Rosenbaum S, Fernandez-Sesma A, Herold BC. Herpes simplex virus 2 (HSV-2) prevents dendritic cell maturation, induces apoptosis, and triggers release of proinflammatory cytokines: potential links to HSV-HIV synergy. Journal of virology 2013 Feb; 87(3).
Versteeg GA, Rajsbaum R, Sánchez-Aparicio MT, Maestre AM, Valdiviezo J, Shi M, Inn KS, Fernandez-Sesma A, Jung J, García-Sastre A. The E3-ligase TRIM family of proteins regulates signaling pathways triggered by innate immune pattern-recognition receptors. Immunity 2013 Feb; 38(2).
Morrison J, Laurent-Rolle M, Maestre AM, Rajsbaum R, Pisanelli G, Simon V, Mulder LC, Fernandez-Sesma A, García-Sastre A. Dengue virus co-opts UBR4 to degrade STAT2 and antagonize type I interferon signaling. PLoS pathogens 2013 Mar; 9(3).
Aguirre S, Maestre AM, Pagni S, Patel JR, Savage T, Gutman D, Maringer K, Bernal-Rubio D, Shabman RS, Simon V, Rodriguez-Madoz JR, Mulder LC, Barber GN, Fernandez-Sesma A. DENV Inhibits Type I IFN Production in Infected Cells by Cleaving Human STING.. PLoS Pathogens 2012 Oct; 8((10)): e1002934doi: 10.1371/journal.ppat.1002934. Epub 2012 Oct 4.
Chiang C, Engel A, Opaluch A, Ramos I, Maestre A, Secundino I, De Jesus P, Nguyen Q, Welch G, Bonamy G, Miraglia L, Orth A, Nizet V, Fernandez-Sesma A, Zhou Y, Barton G, Chanda S. Cofactors required for TLR7- and TLR9-dependent innate immune responses. . Cell Host and Microbe 2012 March 15; 11(3): 306-318.
Berger A, Sommer AF, Zwarg J, Hamdorf M, Welzel K, Esly N, Panitz S, Reuter A, Ramos I, Jatiani A, Mulder LC, Fernandez-Sesma A, Rutsch F, Simon V, König R, Flory E. SAMHD1-deficient CD14+ cells from individuals with Aicardi-Goutières syndrome are highly susceptible to HIV-1 infection. PLoS pathogens 2011 Dec; 7(12).
Varga ZT, Ramos I, Hai R, Schmolke M, García-Sastre A, Fernandez-Sesma A, Palese P. The influenza virus protein PB1-F2 inhibits the induction of type I interferon at the level of the MAVS adaptor protein. PLoS pathogens 2011 Jun; 7(6).
Ramos I, Bernal-Rubio D, Durham N, Belicha-Villanueva A, Lowen AC, Steel J, Fernandez-Sesma A. Effects of receptor binding specificity of avian influenza virus on the human innate immune response. Journal of virology 2011 May; 85(9).
Ashour J, Morrison J, Laurent-Rolle M, Belicha-Villanueva A, Plumlee CR, Bernal-Rubio D, Williams KL, Harris E, Fernandez-Sesma A, Schindler C, García-Sastre A. Mouse STAT2 restricts early dengue virus replication. Cell host & microbe 2010 Nov; 8(5).
Rodriguez-Madoz JR, Belicha-Villanueva A, Bernal-Rubio D, Ashour J, Ayllon J, Fernandez-Sesma A. Inhibition of type I IFN response in human dendritic cells by dengue virus infection requires catalytically active NS2B3 complex. J. Virol 2010 Oct; 84(19): 9760-9774.
Rodriguez-Madoz JR, Bernal-Rubio D, Kaminski D, Boyd K, Fernandez-Sesma A. Dengue virus inhibits the production of type I interferon in primary human dendritic cells. J. Virol 2010 May; 84(9): 4845-4850.
Haye K, Burmakina S, Moran T, García-Sastre A, Fernandez-Sesma A. The NS1 protein of a human influenza virus inhibits type I interferon production and the induction of antiviral responses in primary human dendritic and respiratory epithelial cells. Journal of virology 2009 Jul; 83(13).
Phipps-Yonas H, Seto J, Sealfon SC, Moran TM, Fernandez-Sesma A. Interferon- pretreatment of conventional and plasmacytoid human dendritic cells enhances their activation by influenza virus. PLoS Pathogens 2008 Oct 31; 4(10): e1000193.
Fernandez-Sesma A, Marukian S, Ebersole BJ, Kaminski D, Park MS, Yuen T, Sealfon SC, García-Sastre A, Moran TM. Influenza virus evades innate and adaptive immunity via the NS1 protein. Journal of virology 2006 Jul; 80(13).