Faculty

Mechanisms of murine leukemia virus
and HIV-1 genetic variation

    Research in the Telesnitsky lab addresses the molecular genetics of genome replication for murine leukemia virus (MLV) and HIV-1. Retroviral genomes persist in cells as integrated DNAs, but encapsidated genomes for both these retroviruses consist of two copies of RNA joined in a dimer linkage. Upon infecting a fresh cell, the viral reverse transcriptase copies these RNAs into a DNA intermediate that becomes the integrated provirus.

    During reverse transcription, template switching between RNAs can lead to genetic recombination. Our laboratory discovered that the principal reason genetic recombination is more frequent for HIV-1 than for MLV is differences in RNA trafficking. Thus one major area of research addresses how RNAs associate to form dimers and how they are recruited for virion inclusion.

    Much of our work addresses outcomes of reverse transcription, with a special focus on recombinogenic template switching. We are interested in how the replication machinery selects specific sequences as recombination substrates. Combining our viral genetics/molecular enzymology work with informatics, we discovered that some clinically important HIV-1 variation results when the virus uses portions of its human host’s genetic material as a template for viral genome segments. Ongoing work addresses the roles of viral proteins and template switching in faithful genome synthesis, and the spectra of errors that can give rise to retroviral genetic variability.

    We are also interested in the host RNAs in retroviral particles. RNA, but not the viral genome, is required for retroviral assembly. We have determined that certain host RNAs that usually reside in ribonucleoprotein complexes are enriched in virions in the absence of their cognate structural proteins. We hypothesize that these may be virion structural RNAs.

Selected Publications: 

    Onafuwa, A., An, W., Robson, N., and Telesnitsky, A. (2003) HIV-1 genetic recombination is more frequent than that of Moloney murine leukemia virus despite similar template switching rates J. Virol. 77: 4577-4587.

    Flynn, J.A., An, W., King, S.R., and Telesnitsky, A. (2004) Non-random dimerization of murine leukemia virus genomic RNAs. J Virol 7812129-12139.

    Onafuwa-Nuga, A., Telesnitsky, A, and King, S.R. (2006) 7SL RNA, but not the 54 kd signal recognition particle protein, is an abundant component of both infectious HIV-1 and minimal virus-like particles. RNA 12: 542-546.

    Takebe, Y. and Telesnitsky, A. (2006) Evidence for the acquisition of multi-drug resistance in an HIV-1 clinical isolate via human sequence transduction.  Virology 351: 1-6.

    Duggal, N.K., Goo, L, King, S.R., and Telesnitsky, A. (2007) Effects of homology minimization on Moloney murine leukemia virus template recognition, and frequent tertiary template-directed insertions during non-homologous recombination. J. Virol. 81: 12156-68.