Cellular ER import proteins: Potential targets for antiviral intervention

• Applicant: Dr. Heike Hofmann-Winkler
• Subject Area: Virology
• Term: since 2020
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 438781968

The surface proteins of enveloped viruses mediate viral entry into target cells and constitute potential targets for antiviral intervention. Due to the high mutation rate during viral replication, changes in envelope protein genes can be acquired which may confer resistance against inhibitors. In contrast, cellular proteins required for envelope protein expression or envelope protein mediated host cell entry are genetically stable, and blockade of these factors might allow long-term suppression of viral spread. A recent milestone study showed that certain host cell factors are required for import of nascent envelope proteins into the ER and for flavivirus replication (Zhang et al., Nature 2016, PMID 27383988). Surprisingly, loss of these factors was compatible with cell viability and did not interfere with replication of several viruses outside the flavivirus family. Thus, certain cellular factors facilitating ER import may be attractive targets for antiviral intervention. However, ER import factor choice of viruses is poorly characterized to date, and it is unclear how cells and viruses may compensate for the loss of specific import factors. The aim of the proposed study is to identify factors required for ER import of viral envelope proteins and to elucidate whether they constitute potential targets for antiviral intervention.

• DFG Programme: Research Grants