Munoz, Aldo
Aldo is in the Biochemistry, Molecular and Structural Biology Graduate Program, and joined the CMB Training Program in 2022.
Mentor: Dr. Jose Rodriguez
Pathogenic clade B New World mammarenaviruses (NWMs) are a clade of arenaviruses that have been known to cause severe hemorrhagic fevers in South America. These include the Junin, Machupo, Guaranito, Sabia, and Chapere viruses. Their high mortality rates, ease of transmission, and potential for major public health impact, has caused them to be classified by the National Institute of Allergy and Infectious Diseases as category A pathogens, meaning they pose a very high risk to national security and public health. Although there are fewer than 200 cases per year, the mortality rate for these viruses ranges from 20% to 30%, mostly affecting rural farm workers with limited access to proper treatment.
Treatment for NWMs grows complicated since the glycoproteins of these viruses are poorly conserved with less than 40% sequence similarity across the clade. This makes therapeutics targeting the glycoproteins hyper-specific to a single member of the clade. Therefore, targeting the highly conserved receptor through which they initiate cell entry, human transferrin receptor 1, is a more viable option for broad treatment. Recently, the murine antibody OKT9 was demonstrated as a potential blocker for cell entry by clade B NWMs through steric occlusion of the apical domain, protecting mice from Junin lethal hemorrhagic fever. It also inhibits internalization of other pathogenic NWM pseudoviruses. My interest is understanding at a molecular level how OKT9 is preventing internalization. Through structural studies using X-ray crystallography and CryoEM, we will elucidate the molecular mechanisms of OKT9 binding and lay a foundation for development of therapeutics against NWMs.
