Multidisciplinary research in HIV-1 genetic variation and retroviral RNA
HIV-1 is a member of the retroviridae, whose "retro" name indicates that whereas cells' genetic information flows from DNA to RNA, retrovirus replication cycles include reverse transcription, which generates a DNA copy of the viral RNA genome. Possessing an RNA genome has many interesting implications. For example, our laboratory discovered that differences in gammretrovirus and lentivirus genetic recombination rates reflect the differing ways these viruses tap into host RNA trafficking pathways. After reverse transcription, the integration of viral DNA into the host’s chromosomes makes retroviruses the ultimate genetic parasite.
With their RNA genomes and their proteinaceous cores, retroviruses can be viewed as ribonucleoprotein complexes that cells produce in response to instructions in the viral genome. HIV-1 has been studied extensively because it is an important human pathogen, but the understanding of its nucleic acids lags far behind knowledge of its proteins. Part of the reason for this is that RNAs are less amenable to structural analysis than proteins. Our lab pursues genetic and comparative virology approaches to understanding retroviral RNA-mediated processes. We are also engaged in fruitful collaborations with biophysicists, which have resulting in high-profile publications that are revealing the structures and dynamics of retroviral components. Your training in our laboratory will give you mastery in molecular virology as well as strong exposure to a broad spectrum of complementary approaches for addressing the structures and roles of retroviral nucleic acids, which will provide breadth to your training and nimbleness in your career as a 21st century scientist.
Johnson, SF, Garcia, EL, and Telesnitsky, A. (2012) Moloney murine leukemia virus genomic RNA packaged in the absence of a full complement of wild type nucleocapsid protein. Virology in press
Lu,K., Heng,X., Garyu, L., Monti, S., Garcia, E., Kharytonchyk, S, Dorjsuren, B., Kulandaivel, G., Jones, S., Hiremath, A., Divakaruni, S. LaCotti, C., Barton, S., Tummillo, D., Hosic, A., Edme, K., Albrecht, S., Telesnitsky A, Summers MF (2011) NMR detection of structures in the HIV-1 5’-leader RNA that regulate genome packaging. Science 334, 242-245.
Keene, S.E., King, S.R., and Telesnitsky, A. (2010) 7SL RNA is retained in HIV-1 minimal virus-like particles as an S-domain fragment. J. Virol. 84: 9070.
Johnson, S.F. and Telesnitsky, A. (2010) Retroviral RNA dimerization and packaging: the what, how, when, where, and why. PLoS Pathogens 6:10 e1001007
Miyazaki Y, Irobalieva RN, Tolbert BS, Smalls-Mantey A, Iyalla K, Loeliger K, D'Souza V, Khant H, Schmid MF, Garcia EL, Telesnitsky A, Chiu W, Summers MF (2010) Structure of a conserved retroviral RNA packaging element by NMR spectroscopy and cryo-electron tomography. J. Mol. Biol. 404:751072.
Garcia, E.L., Sim, S., Onafuwa-Nuga, A, King, S.R., Wolin, S.L. and Telesnitsky, A. (2009) Packaging of host mY RNAs by murine leukemia virus may occur early in Y RNA biogenesis. J. Virol. 83:12526-34.
Onafuwa-Nuga, A. and Telesnitsky, A. (2009) The remarkable frequency of HIV-1 genetic recombination. MMBR73: 451-479.