What we do: retroviral replication

Current research

Our current work focuses on molecular genetics of the retroviruses Moloney murine leukemia virus (MLV) and HIV-1. We are particularly interested in the viral genome, which consists of two (generally identical) strands of RNA within viral particles and thus is sometimes considered to be diploid. Once retroviruses enter cells, their RNAs are "reverse transcribed" to generate a DNA copy of the viral genome, which subsequently becomes integrated into the host?s chromosomes.

Retroviral genetic recombination

Genetic recombination is far more frequent for retroviruses than it is for any other class of viruses. We are studying the consequences and regulators of retroviral recombination and also testing related hypotheses, such as that recombination may be a viral fidelity mechanism (that is, that DNA synthesis would be prone to more frequent misinsertion errors if recombination were not possible). You can download our review on recombination (see An and Telesnitsky 2002 AIDS Reviews article on our publications page) to learn more!

Virus/host interactions on the cellular level

All viruses are obligate intracellular parasites, so if you are a virus with an RNA genome, the way the host cell traffics its RNA can dictate what you will inherit. Our laboratory has contributed to recent work showing that the way MLV targets RNAs to nascent virions differs fundamentally from the corresponding process for HIV-1. Much of what is known about RNA trafficking was learned from studies with HIV-1 and with another retrovirus, MPMV, which uses pathways distinct from both MLV and HIV-1. Thus, we hope that our ongoing MLV studies will not only further understanding of retroviral assembly and genetics, but will also advance the more general field of intracellular trafficking.

Reverse transcriptase structure/function interactions

Reverse transcriptase is a small DNA polymerase that is a member of the telomerase enzyme family. It is both a nuclease and a polymerase in a single polypeptide. Crystal structure data is available, retroviral genomes are easily manipulated in the lab, fairly simple enzyme purification strategies have been established, and viral genetics are well advanced. Thus, retroviral reverse transcriptase provides an ideal system for performing structure-function studies that address what determines the properties of this remarkable enzyme both in the test tube and during viral replication. We are fortunate to have a productive on-going collaboration with the crystallographer who solved the MLV RT core structure, Dr. Millie Georgiadis. Much of the work in the Telesnitsky lab to date has been performed on this topic, when it is broadly defined to include studies of enzyme substrate specificity and enzyme properties that affect the outcomes of specific viral replication steps.