My current research interests are focused on the following areas: mechanisms of reverse transcription and recombination; RNA packaging and virus assembly; and interactions between distinct viruses. Retroviral RNA is reverse transcribed to generate viral DNA that integrates into the host genome to form the provirus. Currently, many of the antiretroviral drugs target the step of reverse transcription in the viral life cycle. Recombination occurs frequently during reverse transcription; this process can reassort mutations and increase the variation in the viral population. It has been demonstrated that viral strains with multiple drug resistance can be generated by recombination from strains that are resistant to a single drug. Using in vivo systems, my laboratory is dissecting the mechanisms of reverse transcription and retroviral recombination to gain a better understanding of these very important processes. Retroviruses package their RNA into viral particles specifically through interactions between the viral Gag polyprotein and a region in the viral RNA termed the packaging signal. My laboratory observed that murine leukemia virus (MLV) and spleen necrosis virus (SNV), an avian retrovirus, have a nonreciprocal recognition between their Gag polyproteins and packaging signals. SNV proteins can package RNA containing either the SNV or MLV packaging signal, whereas MLV proteins can package only RNA with the MLV packaging signal. My laboratory is dissecting the cis- and trans-acting elements important for this specific recognition. Using MLV and SNV as model systems, my laboratory observed that viral RNA from distinct viruses can be packaged into a single virion. Furthermore, recombinant retroviruses can be generated from these two viruses. This is the first experiment demonstrating that genetic interaction can occur between distinct retroviruses. My laboratory is currently examining the mechanisms and limitations of these interactions.
| Hu, W S; Pathak, V K (2000) Design of retroviral vectors and helper cells for gene therapy. Pharmacol Rev 52:493-511 |
| Cheslock, S R; Anderson, J A; Hwang, C K et al. (2000) Utilization of nonviral sequences for minus-strand DNA transfer and gene reconstitution during retroviral replication. J Virol 74:9571-9 |
| Anderson, J A; Pathak, V K; Hu, W S (2000) Effect of the murine leukemia virus extended packaging signal on the rates and locations of retroviral recombination. J Virol 74:6953-63 |
