LABORATORY OF VIROLOGY AND INFECTIOUS DISEASE

Hoffmann’s research investigates the mechanisms by which viruses exploit host-cell machinery to establish infection and how cellular factors might be targeted for antiviral intervention. Combining genetic screens with targeted perturbations and biochemical approaches, he studies host factors across virus families, host species, and cell types.

Using gene-trap screening, Hoffmann identified the E3 ubiquitin ligase mind bomb 1 (MIB1) as a host factor critical for the delivery of adenovirus particles to the nucleus during infection. Applying the same approach to respiratory syncytial virus (RSV), he identified SPCA1, a calcium transporter that supports viral maturation and spread. Subsequent studies revealed that SPCA1 promotes infection not only by paramyxoviruses such as RSV, but also by multiple members of the Flaviviridae and Togaviridae families, including West Nile, Zika, and chikungunya viruses. To identify additional host factors shared across diverse viruses, Hoffmann and his colleagues conducted CRISPR screens with multiple flaviviruses and coronaviruses and cross-referenced the results to distinguish conserved from virus-specific host dependencies. This work identified TMEM41B as an essential host factor for both virus families, with a conserved role in viral infection across mammalian, mosquito, and tick cells. Together, these studies have advanced understanding of shared host dependencies among diverse viruses and provided a foundation for evaluating host-directed strategies for broad-spectrum antiviral development.

More recently, Hoffmann has expanded his research to investigate the influence of cellular context on viral infection, with a particular focus on arthropod vectors and tick-borne viruses. His current work examines host factors that regulate viral entry and replication, as well as the establishment and maintenance of persistent infections in tick cells. A major focus is dystroglycan-1, which his research has implicated in the entry of selected tick-borne flaviviruses, including Powassan virus. By developing genetic tools for tick-cell systems and comparing viral requirements in tick and vertebrate cells, Hoffmann aims to define the molecular mechanisms underlying virus–vector interactions and identify host pathways that could inform new strategies to control viral infection and transmission.