Age-dependent poliovirus replication in the mouse central nervous system is determined by internal ribosome entry site-mediated translation.

Department of Microbiology, Columbia University College of Physicians and Surgeons, 701 W. 168th St., New York, New York 10032, USA.
Journal of Virology (Impact Factor: 4.65). 04/2006; 80(6):2589-95. DOI: 10.1128/JVI.80.6.2589-2595.2006
Source: PubMed

ABSTRACT Mouse cells are not permissive for the replication of human rhinovirus type 2 (HRV2). To determine the role of the HRV2 internal ribosome entry site (IRES) in determining species specificity, a recombinant poliovirus (P1/HRV2) was constructed by substituting the poliovirus IRES with the IRES from HRV2. This recombinant virus replicated in all human and murine cell lines examined, demonstrating that the HRV2 IRES does not limit viral replication in transformed murine cells. P1/HRV2 replicated in the brain and spinal cord in neonatal but not adult mice transgenic for the poliovirus receptor, CD155. Passage of P1/HRV2 in mice led to selection of a virus that caused paralysis in neonatal mice. To determine the relationship between HRV2 IRES-mediated translation and replication of P1/HRV2 in mice, recombinant human adenoviruses were used to express bicistronic mRNAs in murine organs. The results demonstrate that the HRV2 IRES mediates translation in organs of neonatal but not adult mice. These findings show that HRV2 IRES-mediated translation is a determinant of virus replication in the murine brain and spinal cord and suggest that the IRES determines the species specificity of HRV2 infection.

  • Source
    Future Virology 03/2007; 2(2):183-192. · 1.00 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The Bunyaviridae is a large and diverse family of viruses whose members infect a wide range of arthropod vectors and animal or plant hosts. Bunyaviruses are distributed worldwide and their promiscuous use of an impressive variety of arthropod vectors amplifies the potential for bunyaviruses to increase their prevalence and geographic range given the right environmental or man-made conditions. Most bunyavirus infections are asymptomatic or present with a mild influenza-like illness. However, some members of the family are important human and veterinary pathogens that are the causative agents of devastating illnesses, including hemorrhagic fever, pulmonary disease, congenital abnormalities, and fatal encephalitis. In this chapter, we discuss the epidemiology, lifecycle, molecular biology, neuropathogenesis, and prevention and treatment strategies for emerging bunyaviruses that are predominantly associated with central nervous disease; these include members of the genera Phlebovirus (Rift Valley fever virus and Toscana virus) and Orthobunyavirus (La Crosse virus and Cache Valley virus).
    Handbook of Clinical Neurology 01/2014; 123C:449-463.
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Like poliovirus, severe infection with enterovirus 71 (EV71) can cause neuropathology. Unlike poliovirus, EV71 is often associated with hand, foot, and mouth disease (HFMD). Here, we established three mouse models for experimental infection with the same clinical isolate of EV71. The NOD/SCID mouse model is unique in developing skin rash, an HFMD-like symptom. While the NOD/SCID model developed limb paralysis and death at near 100% efficiency, the interferon-gamma receptor knockout (ifngr KO) and the stat-1 knockout mice exhibited paralysis and death rates near 78% and 30%, respectively. Productive infection with EV71 depends on viral dose, host age, and inoculation routes. Infectious EV71, and VP1-specific RNA and protein in muscle, brain, and spinal cord, were compared side-by-side between NOD/SCID and stat-1 models before, during, and after disease onset. Spleen fibrosis and muscle degeneration are common in NOD/SCID and stat-1 models. Main differences between these two models include their disease manifestations and cytokine/chemokine profiles. Pathology of the NOD/SCID model includes 1) inflammation and expression of viral VP1 antigen in muscle; 2) increased neutrophils and decreased eosinophils and lymphocytes; 3) hair loss and skin rash. Characteristic pathology of the stat-1 model includes 1) a strong tropism of EV71 for central nervous system; 2) detection of VP1 protein in the Purkinje layer of cerebellar cortex, pons, brainstem, and spinal cord; 3) amplification of microglial cells; 4) dystrophy of intestinal villi. Our comparative studies on these new models by oral or intraperitoneal (i.p.) infection underscored the contribution of host immunity, including interferon-gamma receptor, to EV71 pathogenesis.
    Journal of Virology 08/2014; · 4.65 Impact Factor


Available from