Nathan M. Sherer, PhD
Assistant Professor of Molecular Virology and Oncology
McArdle Laboratory for Cancer Research
School of Medicine and Public Health
University of Wisconsin – Madison
The late stages of the retroviral life cycle involve a series of integrated post-transcriptional regulatory events mediated by interactions between key viral and cellular factors. These stages are initiated at nuclear export of unspliced and partially spliced viral mRNAs, including full-length genomic RNAs (gRNAs) that encode the Gag and Gag-Pol polyproteins that form the viral capsid. For HIV-1, gRNA nuclear export is regulated by the viral Rev protein that multimerizes on the Rev response element (RRE), a cis-acting structural RNA element found in intron-containing viral transcripts, and recruits the cellular chromosomal region maintenance 1 (CRM1) nuclear export receptor through its C-terminal leucine-rich nuclear export signal (NES). It is not fully understood why HIV-1 gRNAs (and some other retroviruses) use the CRM1 pathway, in contrast to other retroviruses such as Mason-Pfizer monkey virus (M-PMV) that lack Rev equivalents and utilize the conventional NXF1/NXT-regulated mRNA nuclear export machinery.
To study HIV-1 and other retroviruses, we have engineered a long-term (>24 h) multicolor, systems-based live cell imaging strategy for directly monitor several viral post-transcriptional regulatory stages (encompassing transcription, RNA nuclear export, translation, intracellular trafficking, and virus particle assembly) all in the context of single cells. I will discuss our recent progress, including the discovery that HIV-1 Rev-dependent RNA exhibits “burst-like” nuclear export kinetics, our finding that Mason-Pfizer monkey virus encodes a cis-acting RNA element that links its RNAs to microtubule motor complexes, and new evidence that many to most viral RNA elements program RNAs for distinct trafficking and translation behaviors. I will also summarize how we are applying our HIV imaging strategy to study the roles of host cellular factors that regulate HIV gene expression and virion production.
On Campus location ONLY.
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