Emerging and re-emerging viruses: biology, pathogenesis and prospection

Abstract

This thematic research project is proposed based on a central backbone of research on viruses of great importance for human health. The proposal comes from five collaborative research groups, led by established professors, and consists of subprojects distributed in four major areas of work: 1) Virus-cell interaction; 2) Pathogenesis of viral infections; 3) Diagnosis and prospection of human viruses; 4) Testing of drugs and antiviral vaccines. The pathogens to be addressed in this Thematic are: the human immunodeficiency virus (HIV); Zika arboviruses (ZIKV), Oropouche (OROV), Mayaro (MAYV), Chikungunya (CHIKV), Dengue (DENV), West Nile (WNV), Yellow Fever (YFV), Saint Louis Encephalitis (SLEV), and Rocio (ROCV); hantaviruses causing pulmonary and cardiovascular syndrome; arenavirus; and the respiratory viruses influenza A (IAV), respiratory syncytial (RSV), metapneumovirus (MPV), rhinovirus (RV), and enterovirus (EV). The great importance of these agents for human health is reflected in the substantial spread of zoonotic viruses in Brazil, causing diseases including congenital syndromes; in the 38 million people living with HIV in the world, and in the high frequencies of respiratory viral infections, the most frequent infections of humankind. In addition to these specific viruses, viromes of human tissues and blood samples will be prospected, as well as of zoonotic viruses as potentials threats to human health. Viruses will be investigated in various experimental models, including studies on entry, assembly, intracellular traffic, and externalization of viruses in exosomes; modes of viral antagonism and modulation of host antiviral factors; viral effects on proteostasis in neurons; viral effects on endoplasmic reticulum stress, autophagy and inflammasome; modulation of cellular inflammatory response in arbovirus infection; cell biology of virus persistence in lymphohematopoietic tissues; arbovirus pathogenesis; cell biology of virus infection in bat cells; humoral response to flaviviruses and their cross-reactions; single-cell analysis of functional genomics of viruses; placental infection and vertical virus transmission; development of broad-spectrum diagnosis of acute febrile and CNS diseases by massive sequencing in MinION and by DNA and peptide microarrays; prospection and eco-epidemiology of zoonotic viruses; viromes of patients with acute febrile illness; arbovirus detection in avian fauna; and development of antiviral drugs and vaccines. The scientific challenges are clear, and we are convinced that we can tackle them on the basis of well-planned strategies, with collaborations between teams, including technicians, postdocs, postgraduate and undergraduate students. In addition, the Virology Research Center, created at USP Ribeirão Preto thanks to FAPESP, has a well equiped structure, with BSL2 and BSL3 laboratories, an experimental vivarium, and a solid support network in the institution's multiuser facilities. This project has the potential to make important discoveries in virology, some of fundamental nature, that could expand knowledge and even serve as a basis for developing products. (AU)