UCSF

Viruses have long been noted to be composed simply of nucleic acid and protein. This thesis describes this confluence of science of viruses at the interface of genomics and proteomics. Chapter 2 describes the discovery of klassevirus, a new picornavirus in pediatric diarrhea. Chapter 3 shows that klassevirus is likely a human pathogen given the seroconversion of klassevirus-positive individuals against a klassevirus non-structural protein that is not present in the picornavirus virion. Subsequent work failed to obtain a culturable virus from klassevirus-positive stool samples, enabling the transition to culture-independent methods of characterizing picornavirus-host protein interactions. Chapter 4 describes the use of affinity purification mass spectrometry to discovery a novel picornavirus 3A-ACBD3-PI4KB complex that promotes viral replication in the enteroviruses and kobuviruses. Chapter 5 extends upon the methodology to describe a novel host protein interactor of ACBD3 (TBC1D22A/B), whose interaction is altered specifically by the kobuvirus 3A protein. This complex also demonstrates significant interaction with the klassevirus 3A protein, suggesting that the AP-MS work may inform the biology of the uncultured virus. Finally, chapter 6 describes future directions that are opened up by this work.