The Fernandez-Sesma group has developed and optimized human primary cell systems to study the interactions of DENV and other viruses with human primary immune cells, such as monocytes, dendritic cells (DCs) and macrophages and has recently developed a human tonsil system to study DENV infections. Using these systems her group identified the interferon (IFN) antagonist for DENV, the NS2B3 protease complex, which inhibits the production of this important antiviral cytokine in primary human cells by cleaving the adaptor molecule STING, and more recently we found that components of the viral protease also target cGAS for degradation in infected cells. The Fernandez-Sesma lab is currently characterizing the mechanisms of immune evasion by DENV in primary human systems and developing novel model systems to study this virus, including mice transgenic for human genes that may facilitate DENV infection in more immune competent systems than the ones currently available.
Our research team also participates in several past and current multi-investigator projects on HIV, influenza and dengue virus. Some of the past projects include a department of defense (DARPA) funded project together with several other investigators from other institutions to study evolution and fitness of DENV in mosquito and mammalian systems. We also participated in a NIH-funded multi-investigator program project to study innate immunity in HIV (HINT) (in which studying the role of those factors on HIV infections of primary human cells. Of the current projects, two of them focus on influenza virus. One of them, Center for Research on Influenza Pathogenesis (CRIP), led by Dr. Garcia-Sastre focuses on influenza virus immune evasion strategies using human systems, and is one of the NIH/NIAID-funded Centers of Excellence of Influenza Research and Surveillance (CEIRS). In particular, we study how influenza viruses of avian origin interact with cells of the immune system as compared to human influenza viruses via their receptor binding properties. We also participate in the NIH-funded Program for Research on Immune Modeling and Experimentation (PRiME), led by Dr. Stuart Sealfon, and we focus on the infection and immune antagonistic kinetics of influenza virus in primary human epithelial systems.
More recently Dr. Fernandez-Sesma was able to gather an impressive team of existing and new collaborators from ISMMS, as well as several other institutions to investigate the human innate immune responses to DENV in infected and vaccinated individuals as well as ex vivo infections of primary human systems with DENV in as part of the NIH/NIAID Human Immunology Human Project Consortia (HIPC). Our center, led by Dr. Fernandez-Sesma (PI) and Dr. Eva Harris (Co-PI), named Dengue Human Immunology Project Consortia( DHIPC), is focused on the study of human immune responses to dengue virus after infection and vaccination using state of the art immune profiling, proteomics, genomics and systems biology approaches. Recently, the project also includes studies on human immune responses to Chikungunya and Zika viruses.