Bryan Cullen

My laboratory has for sometime been interested in understanding the molecular biology of the replication cycle of the pathogenic retrovirus HIV-1. Because HIV-1 gene expression is primarily regulated by specific RNA:protein interactions, my laboratory has also become interested in the more general area of RNA sequence mediated gene regulation, including nuclear mRNA export and the phenomenon of RNA interference.

In the past, my laboratory has worked extensively on Tat, the transcriptional regulator encoded by HIV-1, and on Rev, a virally encoded nuclear mRNA export factor. Our major focus at present is a third HIV-1 regulatory protein termed Vif. In the absence of Vif, HIV-1 virions are produced normally but are largely non-infectious. It has now been demonstrated that Vif functions to block an innate human antiretroviral defense pathway that relies on a factor called APOBEC3G or CEM15. In the absence of Vif, APOBEC3G is packaged into virions and induces degradation of the HIV-1 genome during reverse transcription in target cells. Vif directly interacts with APOBEC3G and thereby allows reverse transcription to proceed unimpeded. Among other issues, we are currently interested in how APOBEC3G is packaged into virions and in how Vif blocks APOBEC3G function. The role of APOBEC3G in cellular defense against other retroviruses and retrotransposons is also an area of interest.

A second major research area in my group relates to how microRNA precursors are processed to yield mature microRNAs and how microRNAs, and the closely related small interfering RNAs, function in human cells. We were the first group to demonstrate overexpression of human microRNAs and therefore have a system in place which should allow us to make rapid progress in this area. We also remain interested in using RNA interference to determine the role of specific cellular factors in different processes, including HIV-1 replication and nuclear mRNA export.