Mammals have complicated antiviral innate immunity to combat viral infection and this poses a strong selection pressure on the viruses. As a result, many viruses have evolved different strategies to disrupt the function of hosts’ antiviral innate immunity. Herpes simplex virus type 1 (HSV-1) is one of the examples. HSV-1 is a common and important human pathogen. HSV-1 infection induces type I interferons (IFNs) which restrict viral replication potently. To ensure persistent infection and successful replication, HSV-1 encodes several IFN-suppressing proteins. One example is Us11. Interaction between Us11 and various cellular proteins, such as PKR, RIG-I and PACT, were shown by other studies. However, exactly how Us11 suppresses IFN function remains to be elucidated. In this study, I discovered that Us11 specifically inhibits PACT induced activation of RIG-I. In HSV-1 infected cells, PACT and Us11 associate with each other tightly and this interaction prevents the interaction of PACT with RIG-I. It was also found that RNA binding domains on both PACT and Us11 are important for the association. In infection experiments, the increased production of IFN- during the infection of PACT-competent cells with Us11-deficient HSV-1 recombinant virus was not observed in infected PACT-compromised cells, suggesting the requirement of PACT for Us11 suppression of IFN production. To conclude, this study provides an explanation for Us11 antagonism of IFN production. My findings suggest that PACT is a novel target of HSV-1 IFN-antagonizing protein Us11. / published_or_final_version / Biochemistry / Master / Master of Philosophy

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Thesis (PhD)--University of South Australia, 2000

Thesis (PhD)--University of South Australia, 2000

Thesis (Ph. D.)--School of Pharmacy and Dept. of Chemistry. University of Missouri--Kansas City, 2005. / "A dissertation in pharmaceutical sciences and chemistry." Advisor: Ashim K. Mitra. Typescript. Vita. Description based on contents viewed Nov. 21, 2007; title from "catalog record" of the print edition. Includes bibliographical references (leaves 238-258). Online version of the print edition.

Diss. (sammanfattning) Stockholm : Karol. inst. / Härtill 8 uppsatser.

Thesis (Ph. D.)--University of Chicago, Dept. of Biochemistry and Molecular Biology. / Includes bibliographical references. Also available on the Internet.