Andrew P. Rice Ph.D.

Rice Lab Website

Our general research interest is the regulation of gene expression during viral infection.   Studies of viral gene regulation contribute to the understanding of important human pathogens and often lead to insight into general biological processes that have broad applicability to many areas of biology.  During the past several years, we have largely focused on gene regulation during human immunodeficiency virus (HIV) infection.  We have investigated the mechanism of action of the viral transcriptional activator protein known as Tat.  Tat is unusual among transcriptional activator proteins in that it is targeted to cellular RNA polymerase II through binding to a promoter-proximal RNA element known as TAR, where it then acts to greatly stimulate transcriptional elongation of the integrated HIV provirus.  We and others have obtained evidence that in order to activate transcription elongation, Tat targets the carboxyl terminal domain (CTD) of the largest subunit of RNA polymerase II for modification by phosphorylation.  It is believed that CTD phosphorylation activates transcription by stimulating the promoter clearance of transcription complexes and/or converting elongation-deficient transcription complexes to highly processive complexes.

Several years ago, we identified a cellular serine/threonine protein kinase, now termed P-TEFb, which is the crucial co-factor that the Tat protein binds to, resulting in phosphorylation of the CTD and the subsequent activation of transcription of the viral genome.  Core P-TEFb is composed of two subunits - Cdk9 is the catalytic subunit and Cyclin T1 is a regulatory subunit that makes protein-protein contact with Tat.  Our current studies include further investigation of the molecular mechanisms involved in P-TEFb and Tat function.  We are particularly interested in investigating the normal cellular roles and regulation of P-TEFb in cell types relevant to HIV infection, namely CD4+ T cells and monocytes/macrophages.  We are hopeful that our future studies will contribute to the understanding of fundamental principles of gene regulation in both viral and cellular systems.

Given the laboratory’s long standing interest in host-cell interactions, we are also involved in a project to identify cellular proteins that play a role in the pathogenesis of influenza virus infection.  Highly virulent strains of H5N1 avian influenza viruses are currently circulating in birds in Asia, Europe, and Africa.  The NS1 protein of avian viruses has been shown to be associated with virulence.  A critical feature of the avian NS1 protein is the presence of a protein domain at its carboxyl terminus termed the PDZ-ligand domain.  This domain was predicted to associate with cellular PDZ proteins, a large class of proteins that are typically involved in cell-cell contact and cellular migration.  It is notable that H5N1 viruses that have recently infected humans with an approximate 50% mortality rate express an NS1 protein with the PDZ-ligand domain.  The goal of our avian influenza project is to identify cellular PDZ proteins that are targeted by the NS1 PDZ-ligand domain and examine their contribution to viral pathogenesis.

Rice Lab Website

Recent Publications (PubMed)

Liou, L.-Y., Haaland R.E., Herrmann, C.H., and Rice, A.P.   (2006)  Cyclin T1 but not cyclin T2a is induced by a post-transcriptional mechanism in PAMP-activated monocyte-derived macrophages.  Journal of Leukocyte Biology 79:388-396.

Wang, Y. and Rice, A.P.  (2006)  Interleukin-10 inhibits HIV-1 replication in human macrophages through the induction of cyclin T1 proteolysis.  Virology 352:485-492.

Liu, H., Dow, E.C., Arora, R., Kimata, J.T., Bull, L.M., Arduino, R.C., and Rice. A.P.  (2006)  Integration of human immunodeficiency virus type 1 in untreated infection occurs preferentially within genes.  Journal of Virology 80:7765-7768.

Yu, W., Wang, Y., Shaw, C., Qin, X.-F., and Rice, A.P.  (2006)  Induction of HIV-1 Tat co-factor cyclin T1 during monocyte differentiation is required for the regulated expression of a large portion of cellular mRNAs.  Retrovirology 3:32.

Sung, T.-L. and Rice, A.P.  (2006)  Effects of prostratin on cyclin T1/P-TEFb function and the gene expression profile in primary resting CD4+ T cells.  Retrovirology 3:66.

Yu W., Ramakrishnan R., Wang Y., Chiang K., Sung T.-L., Rice A.P. (2008) Cyclin T1-Dependent Genes in Activated CD4+ T and Macrophage Cell Lines Appear Enriched in HIV-1 Co-Factors. PLoS ONE 3(9): e3146.

Wang, Y., Dow, E.C., Liang, Y.-Y., Ramakrishnan, R., Lin X., Feng, X.-H., and Rice A.P.  (2008). Phosphatase PPM1A regulates phosphorylation of Thr-186 in the Cdk9 T-loop.  Journal of Biological Chemistry.  283:33578-84.  Epub Oct 1, 2008.  Epub Oct1, 2008.

Sung, T-L and Rice, A.P.  (2009). MicroRNA-198 inhibits HIV-1 gene expression and replication and its mechanism of action appears to involve repression of Cyclin T1 expression.  PLoS Pathogens.  E10000263. Epub2009 Jan16.