Huang Lab Research
We study the molecular biology of Sindbis virus, to understand the mechanism of RNA synthesis using RNA templates. We have identified the cis-acting sequences for viral replication and transcription, and we are using an in-vivo library selection method to identify the sequence requirements of the cis-acting sequences. We are also working on identifying the viral proteins that recognize the cis-acting sequences. Our current focus is to characterize in detail how the viral promoter is recognized, by viral and host transcription factors, during initiation of mRNA synthesis.
Our understanding of the molecular biology of Sindbis virus has led to two types of practical applications. First, it has suggested a novel and general approach for designing antiviral drugs, targeting highly conserved elements of the viral genome, including the viral recognition of the cis-acting sequences for initiation of replication and transcription,. It promises to provide broad-spectrum antiviral drugs that are effective against the virus and having minimal impact on host processes, and with very low probabilities of drug-resistance. We are using Sindbis virus as a model system to test this novel approach.
Second, we have developed a series of RNA virus gene expression vectors, derived from Sindbis virus, that give rapid and efficient expression of foreign genes in a wide range of host cells. The Sindbis virus vectors are being used by many research groups to express specific RNAs and proteins in cultured cells and in animals. In our laboratory, we will be using them to express and characterize human developmental gene regulators that are up-regulated during the monocytic differentiation of a human promyelocytic leukemia cell line.