Research Interests

Retroviruses have cleverly evolved to utilize a diverse array of host cell factors during their replication cycles. While a few of these factors (i.e., viral receptors and transcription factors) have been identified for some retroviruses, it is quite clear that retroviruses depend on many different kinds of cellular factors (proteins, lipids, fatty acids) to successfully complete their replication cycles. The understanding of these vitally important virus-host interactions will provide the framework for identifying/designing novel antiviral therapeutics to interfere with retroviral replication.

My laboratory has been searching for cytoplasmic proteins that are required for establishing a persistent viral infection and for assembling progeny viruses for subsequent rounds of infection.

Several candidate host cell proteins have been identified using a genetic screen to search for the cellular genes encode proteins required for retrovirus replication. Interestingly, all of the cellular proteins found to date belong to family of proteins that are thought to be involved in regulating ubiquitin-dependent proteolysis. This is consistent with the findings of others that ubiquitin is packaged into retroviral particles and that ubiquitin-dependent proteosomes play a key role during the release of progeny viruses from the plasma membrane. To this end, we are determining the precise role these recently identified regulators of ubiquitination play during retroviral replication.

The second focus of my laboratory is to identify the mechanism(s) by which the retroviral capsid protein, Gag, is transported through the cytoplasm to the plasma membrane. For this, we are using a combination of real-time fluorescent confocal microscopy, FRET (fluorescent resonance energy transfer) to document the precise pathway of cytoplasmic protein transport and to screen for mutant cell lines that are deficient for this obligatory step during viral replication.

Recent Publications

• Weldon Jr., R. A., W. B. Parker, M. Sakalian, and E. Hunter. 1998. Type D retrovirus capsid assembly and release are active events requiring ATP. J. Virol. 72:3098-3106.
• Sakalian, M., S. D. Parker, R. A. Weldon, Jr., and E. Hunter. 1996. Synthesis and assembly of retrovirus Gag precursors into immature capsids in vitro. J Virol. 70:3706-3715.
• Weldon Jr., R. A., and E. Hunter. 1996. Molecular requirements for retrovirus assembly, p. 381-410. In W. Chiu, R. M. Burnett, and R. L. Garcea (eds), Structural Biology of Viruses. Oxford University Press, New York, NY.
• Krishna, N. K., R. A. Weldon Jr., and J. W. Wills. 1996. Transport and Processing of the Rous sarcoma virus Gag protein in the endoplasmic reticulum. J Virology. 70:1570-1579.
• Weldon, R. A., Jr., and J. W. Wills. 1993. Characterization of a small (25-kilodalton) derivative of the Rous sarcoma virus Gag protein competent for particle release. J Virol. 67:5550-5561.