The roles of chemokines in rabies virus infection: Overexpression may not always be beneficial

Department of Pathology, College of Veterinary Medicine, University of Georgia, Athens, GA 30602, USA.
Journal of Virology (Impact Factor: 4.65). 10/2009; 83(22):11808-18. DOI: 10.1128/JVI.01346-09
Source: PubMed

ABSTRACT It was found previously that induction of innate immunity, particularly chemokines, is an important mechanism of rabies virus (RABV) attenuation. To evaluate the effect of overexpression of chemokines on RABV infection, chemokines macrophage inflammatory protein 1alpha (MIP-1alpha), RANTES, and IP-10 were individually cloned into the genome of attenuated RABV strain HEP-Flury. These recombinant RABVs were characterized in vitro for growth properties and expression of chemokines. It was found that all the recombinant viruses grew as well as the parent virus, and each of the viruses expressed the intended chemokine in a dose-dependent manner. When these viruses were evaluated for pathogenicity in the mouse model, it was found that overexpression of MIP-1alpha further decreased RABV pathogenicity by inducing a transient innate immune response. In contrast, overexpression of RANTES or IP-10 increased RABV pathogenicity by causing neurological diseases, which is due to persistent and high-level expression of chemokines, excessive infiltration and accumulation of inflammatory cells in the central nervous system, and severe enhancement of blood-brain barrier permeability. These studies indicate that overexpression of chemokines, although important in controlling virus infection, may not always be beneficial to the host.

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Available from: Yi Kuang, Aug 21, 2015
    • "It should be noted that although overexpression of cytokines/chemokines has important roles in controlling virus infection and RABV attenuation, certain cytokines/ chemokines, such as RANTES or IP-10, when overexpressed, are detrimental (Zhao et al. 2009). It has been shown that when RANTES or IP-10 was overexpressed, the RABV pathogenicity in mice was increased owing to persistent and highlevel expression of chemokines, extensive infiltration of inflammatory cells in the CNS, and severe enhancement of BBB permeability (Zhao et al. 2009). Therefore, much work should be performed in the future to comprehensively investigate the physiological effect of cytokines/ chemokine expression before RABVs overexpressing cytokines/chemokines are to be developed to treat clinical rabies or other CNS diseases due to the complex responses triggered by cytokines/chemokines. "
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    • "Samples of culture medium were harvested at 12, 24, 48, 72 h post-inoculation (p.i.). Virus titer was determined in NA cells by the dFA as described (Zhao et al., 2009). Fig. 1. "
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