Anisa Kaenjak Angeletti, Phd

Biography

 Membership, American Society for Microbiology (ASM), 1989-present Membership, American Association for Advancement of Science (AAAS), 1990-present

Research Interest

 My research interest is in messenger RNA turnover in mammalian cells induced by viral infections. Stability of mRNA controls the translatability of gene products. Viruses perturb this dynamic in order to take advantage of cellular resources for the purpose of viral replication. I use the Herpes simplex virus type 1 (HSV-1) as a model for my study. Herpes simplex virus (HSV) is a member of alpha-or neuro-tropic herpesviruses, which are enveloped DNA viruses. HSV has a wide range of susceptible host cells and causes diseases in humans from oral cold sores to ocular and genital lesions, and is a major cause of neonatal infections. Approximately 60 million people in the US are chronically infected with HSV. HSV-1 also has a potential as a vector for gene therapy to neurons. HSV encodes a protein known as virion host shutoff (vhs) protein, which mediates massive destruction of both cellular and viral mRNAs in infected cells without affecting rRNA or tRNA. The biological activity of the vhs protein results in a shutoff of host cell protein synthesis. The precise mechanism by which vhs specifically targets mRNA for degradation in infected cells remains unclear. My research is aimed at understanding how the vhs protein functions and how it induces mRNA degradation specifically without affecting rRNA and tRNA.How does the vhs protein specifically target mRNA for degradation in infected cells? The cell-free assays of vhs activity fail to mimic all the in vivo properties of the vhs protein. In particular, mRNA and non-mRNA substrates are degraded to similar extents. I aim to understand the underlying mechanism controlling the target specificity of the vhs protein of HSV-1 in infected cells. I have discovered that the vhs-mediated mRNA decay activity is strictly dependent upon the 5'cap structure of mRNA targets in infected cells. It is well known that the 5'cap structure of mRNA is important in both mRNA stability and translation initiation. But surprisingly, I found that the 3' poly(A) tail of the RNA molecule is not required for vhs targeting. I also discovered that the internal ribosome entry site (IRES) located in the 5' untranslated region (UTR) of some cellular mRNAs, but not in the intercistronic region of a bicistronic mRNA, can block the vhs activity to target mRNA for degradation in infected cells. Important questions to be addressed are: