Skip NavigationSkip to Content
Return Return to Search Results

Attenuation of Neurovirulence, Biodistribution, and Shedding of a Poliovirus:Rhinovirus Chimera after Intrathalamic Inoculation in Macaca fascicularis

  1. Author:
    Dobrikova, E. Y.
    Goetz, C.
    Walters, R. W.
    Lawson, S. K.
    Peggins, J. O.
    Muszynski, K.
    Ruppel, S.
    Poole, K.
    Giardina, S. L.
    Vela, E. M.
    Estep, J. E.
    Gromeier, M.

  2. Author Address

    [Dobrikova, Elena Y.; Goetz, Christian; Walters, Robert W.; Lawson, Sarah K.; Gromeier, Matthias] Duke Univ, Med Ctr, Dept Surg, Div Neurosurg, Durham, NC 27710 USA. [Peggins, James O.] NCI, Toxicol & Pharmacol Branch, Frederick, MD 21701 USA. [Muszynski, Karen] NCI, Biol Res Branch, Frederick, MD 21701 USA. [Ruppel, Sheryl; Poole, Karyol; Giardina, Steven L.] NCI Frederick, Biopharmaceut Dev Program, SAIC Frederick Inc, Frederick, MD USA. [Vela, Eric M.; Estep, James E.] Battelle Mem Inst, Columbus, OH USA.;Gromeier, M (reprint author), Duke Univ, Med Ctr, Dept Surg, Div Neurosurg, Durham, NC 27710 USA;grome001@mc.duke.edu
    1. Year: 2012
    2. Date: Mar
  2. Journal: Journal of Virology
    1. 86
    2. 5
    3. Pages: 2750-2759
  4. Type of Article: Article
  5. ISSN: 0022-538X
  1. Abstract:

    A dependence of poliovirus on an unorthodox translation initiation mode can be targeted selectively to drive viral protein synthesis and cytotoxicity in malignant cells. Transformed cells are naturally susceptible to poliovirus, due to widespread ectopic upregulation of the poliovirus receptor, Necl-5, in ectodermal/neuroectodermal cancers. Viral tumor cell killing and the host immunologic response it engenders produce potent, lasting antineoplastic effects in animal tumor models. Clinical application of this principle depends on unequivocal demonstration of safety in primate models for paralytic poliomyelitis. We conducted extensive dose-range-finding, toxicity, biodistribution, shedding, and neutralizing antibody studies of the prototype oncolytic poliovirus recombinant, PVS-RIPO, after intrathalamic inoculation in Macaca fascicularis. These studies suggest that intracerebral PVS-RIPO inoculation does not lead to viral propagation in the central nervous system (CNS), does not cause histopathological CNS lesions or neurological symptoms that can be attributed to the virus, is not associated with extraneural virus dissemination or replication and does not induce shedding of virus with stool. Intrathalamic PVS-RIPO inoculation induced neutralizing antibody responses against poliovirus serotype 1 in all animals studied.

    See More

  1. Keywords:

External Sources

  1. View Full Text
  2. DOI: 10.1128/jvi.06427-11
  3. View record in Web of Science®
  4. WOS: 000300536800032

Library Notes

  1. Fiscal Year: FY2011-2012
NCI at Frederick

You are leaving a government website.

This external link provides additional information that is consistent with the intended purpose of this site. The government cannot attest to the accuracy of a non-federal site.

Linking to a non-federal site does not constitute an endorsement by this institution or any of its employees of the sponsors or the information and products presented on the site. You will be subject to the destination site's privacy policy when you follow the link.

ContinueCancel