Bryan R. Cullen, PhD
James B. Duke Professor
Director, Center for Virology

My laboratory has for some time 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 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 APOBEC3G and other members of the APOBEC3 protein family.   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 interested in how APOBEC3G is packaged into virions and in how Vif blocks APOBEC3G function.   The role of APOBEC3G family members in cellular defense against other retroviruses and retrotransposons is also a major area of current interest.

A second 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 systems in place which have allowed us to make good progress in this area.   This has led to several publications from my laboratory characterizing the processing pathway and function of human miRNAs.   In addition, we have recently demonstrated that several pathogenic human herpesviruses express viral miRNAs in infected cells and we are currently very interested in identifying the mRNA targets for these viral miRNAs and in determining their contribution to viral pathogenesis.