Author interview: Kriti Biligiri is a graduate student at CSIR-IGIB, where she studied the cell biology of viruses, which led to interesting discoveries during her PhD.
Novel forms of a nuclear protein formed phase-separated condensates in the cytoplasm in response to RNA viral invasion. This protein was recruited into cytoplasmic viral organelles to facilitate replication.
Viral proteins undergo constant mutations, which has made therapeutic targeting of these proteins extremely challenging. To design antiviral drugs, another strategy would be to target host proteins supporting viral replication. However, in the field of virology, the molecular details of how the host responds to viral invasion remains to be well-understood. This involves identifying the host factors interacting directly with the viral components to aid its establishment or propagation within the organism.
This study is the first to identify a cytoplasmic form and function of this host protein, which can potentially be targeted for anti-viral therapy.
– Dr. Shravanti Rampalli
In this study, while we were using viruses as vectors to deliver transgenes into the host, we observed that our host protein of interest demonstrated an unusual pattern of localization. The host protein, EHMT1, is an epigenetic modifier, which was strongly believed to be a nuclear protein, but we observed this protein forming cytoplasmic condensates in response to viral invasion. Further, we identified that EHMT1 expresses a cytoplasmic form, which gets utilized by the virus to build its replication organelles in the cytoplasm. Targeting EHMT1 prevented the formation of these replication organelles, thereby reducing viral replication. Overall, a serendipitous observation led us to unravel a completely novel role of a host protein, which can be a potential target for anti-viral therapy.
Reference: A cytoplasmic form of EHMT1N methylates viral proteins to enable inclusion body maturation and efficient viral replication. Biligiri KK, Sharma NR, Mohanty A, Sarkar DP, Vemula PK, et al. (2024) A cytoplasmic form of EHMT1N methylates viral proteins to enable inclusion body maturation and efficient viral replication. PLOS Biology 22(11): e3002871. https://doi.org/10.1371/journal.pbio.3002871
